Clinical trial NCT03715829
Conditions: Active Non-segmental Vitiligo
Sponsor: Pfizer
Start date: 2018-11-26; Completion date: 2021-02-05
Enrollment: 366 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2b, randomized, double blind, parallel group, multicenter study with an extension period. The study will have a maximum duration of approximately 60 weeks. This includes an up to 4 weeks Screening Period, a 24 week dose ranging period, an up to 24 week extension period and a 8 week Follow up Period.

Detailed description:

Arms: arm 1: Induction dose 1 given once a day(QD) for 4 weeks followed by maintenance dose A given QD for 20 weeks arm 2: Induction dose 2 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks arm 3: Maintenance dose A given QD for 24 weeks arm 4: Maintenance dose B given QD for 24 weeks arm 5: Maintenance dose C given QD for 24 weeks arm 6: Placebo given QD for 24 weeks arm 7: 4 week drug holiday (no drug given) followed by PF-06700841 oral tablet QD for 20 weeks arm 8: Induction dose 1 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks in conjunction with narrow band UVB phototherapy arm 9: Induction dose 1 given QD for 4 weeks followed by maintenance dose A given QD for 20 weeks arm 10: Maintenance dose A given QD for 24 weeks arm 11: Maintenance dose B given QD for 24 weeks arm 12: Observation period for 24 weeks
Interventions: intervention 1: PF-06651600 intervention 2: PF-06651600 intervention 3: PF-06651600 intervention 4: PF-06651600 intervention 5: PF-06651600 intervention 6: placebo intervention 7: PF06700841 intervention 8: narrow-band UVB phototherapy
Intervention descriptions: intervention 1: Induction dose 1. Oral tablet taken QD intervention 2: Induction dose 2. Oral tablet taken QD intervention 3: Maintenance dose A. Oral tablet taken QD intervention 4: Maintenance Dose B. Oral tablet taken QD intervention 5: Maintenance Dose C. Oral tablet taken QD intervention 6: placebo intervention 7: Oral tablet taken QD intervention 8: Phototherapy will be combined with PF-06651600

Protocol documents:
Prot_000.pdf: 


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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 5
26 June 2020

In the Schedule of Activities, Protocol Summary, 
Section 1.2.4 Study Rationale, Section 2 Study 
Objectives and Endpoints, Section 3 Study 
Design, Section 7.4 Clinical Efficacy 
Assessment, Section 7.7 Photography, and 
Section 9 Data Analysis/Statistical Methods, 
added central read Facial Vitiligo Area Scoring 
Index (facial-VASI) as the new primary 
endpoint. Added new key secondary endpoint: 
Proportion of subjects achieving central read 
facial-VASI75 (defined as at least 75% 
improvement in central read facial-VASI from 
baseline) at Week 24.
Rationale: As this is an unprecedented 
indication, there has been limited clinical trial 
experience with the VASI and facial-VASI 
scoring for de-pigmented vitiliginous lesions.
Discrepancies have been identified by an 
external blinded expert consultant in preparation 
for the protocol specified interim analysis.
Based on the digital photographs available, total 
body VASI scores cannot be evaluated by a 
central reader. Due to this limitation and in 
order to preserve the scientific integrity of the 
study, the primary endpoint is changed from the 
percent change from baseline in total body VASI 
at Week 24 to percent change from baseline in 
central read facial-VASI at Week 24. Central 
read facial-VASI75 score will be added as a key 
secondary endpoint. 

In the Section 2 Study Objectives and Endpoints, 
added new exploratory endpoint: proportion of 
subjects achieving “very much improved” on 
patient global impression of change in vitiligo 
(PGIC-V). 
Rationale: This change is to correct the editorial 
error and to be consistent with the scaling of 
PGIC on evaluation of improvement assessed as 


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“very much improved” and “much improved”.

In the Section 7.4.3 Facial Vitiligo Area Scoring 
Index Site Assessment, clarification added that 
the site assessment facial-VASI will be 
performed by the investigator(s). 
Rationale: To differentiate site assessment and 
central assessment facial-VASI. 

In Section 9.1 Sample Size Determination, the 
sample size rationale was updated to reflect the 
assumptions for the new primary endpoint, 
central read facial-VASI.  
Rationale: The sample size rationale is updated 
to be aligned with the new primary endpoint.

In Section 9.2 Efficacy Analysis, the analysis of 
the primary endpoint and secondary endpoints 
were updated. 
Rationale: The analysis is updated to be aligned 
with the new primary and key secondary 
endpoint. 

In Section 9.5 Safety Analysis during the Dose 
Ranging Period, the detail of the analysis is 
removed.  
Rationale: The detail of the analysis will be 
provided in the statistical analysis plan. 

In the Appendix 11, added Alternative Measures 
During Public Emergencies.
Rationale: The Alternative Measures 
During Public Emergencies added to address 
alternative protocol actions to follow during 
COVID-9 pandemic.
Minor administrative changes and sentence 
revisions made throughout the document.
Amendment 4
04 November
2019

In the Cover page, added IND number for 
PF-06700841. 




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Committees, additional tests or procedures that 
are not part of the study but that could be related 
to the study may be requested. 
Rationale: The paragraph is added to provide 
clarity to support safety adjudication process. 

In Appendix 2, clarification was provided for 
Prohibited Concomitant Medications related to 
applicability to PF-06651600 and PF-06700841.
Minor administrative changes and sentence 
revisions made throughout the document.
Amendment 3 
02 July 2019
Changes requested from the Italian Medicines 
Agency (AIFA).

In the Section 1.2.5 Summary of benefits and 
risks, added risk-benefit assessment.

In the Section 4.2 Exclusion Criteria, removed 
interferences of the Sponsor, through the 
Sponsor medical monitor, in the clinical choices 
of the investigator for the eligibility of patients 
from criteria #3, 8, 10, and 16.
Amendment 2
14 June 2019
Changes requested from The Federal Institute for 
Drugs and Medical Devices (Bundesinstitut für 
Arzneimittel und Medizinprodukte, BfArM) for 
Germany. 

In the Schedule of Activities and Section 6.1 
Screening, added statement that subjects will be
provided with an emergency ID card.

In the Schedule of Activities and Section 7 
Assessments, added erythrocyte sedimentation 
rate (ESR) testing to be performed at local 
laboratory at every visit. These changes are in 
effect for Germany only.

In the Section 1.2.4.1 PF-06651600 Dose 
Rationale, added rationale for administering 10 
mg PF-06651600 QD in the Dose Ranging 
Period not in the Extension Period.


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
In the Section 4.2 Exclusion Criteria, added 
exclusion criterion for subjects who have 
galactosemia (galactose-1-phosphate-
uridylyltransferase or UDP-galactose-4-
epimerase or galactokinase deficiency; Fanconi 
Bickel syndrome), a congenital lactase 
deficiency or glucose-galactose malabsorption.

In the Section 4.2 Exclusion Criteria, added 
exclusion criterion for subjects whose diabetes 
mellitus is poorly controlled.

In the Section 8 Adverse Event Reporting, added 
definitions of adverse reaction (AR), serious 
adverse reaction (SAR), and suspected 
unexpected serious adverse reactions (SUSAR).

In the Appendix 2 Prohibited Concomitant 
medications, added Rosuvastatin as a sensitive 
substrate to BCRP. This change is in effect for 
Germany only.

Minor administrative changes and sentence 
revisions made throughout the document.
Amendment 1
04 March 2019

In the Schedule of Activities, Section 2 Study 
Objectives and Endpoints, and Section 7 
Assessments, added target lesions(s) 
assessments. 
Rationale: Target lesion(s) assessments are 
added to provide opportunity to evaluate the 
change of extent of depigmentation of stable
lesion and segmental lesion (if applicable) during 
the study to support the extrapolability of results 
across vitiligo types.

In the Schedule of Activities and Section 7 
Assessments, details of Dermoscopy assessment
are revised.
Rationale: Details of Dermoscopy assessment are 
revised to provide a clearer guidance for the site. 

In the Section 2 Study Objectives and Endpoints, 
added exploratory Endpoints: absolute change 


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from baseline in facialVASI and VES in the 
Dose Ranging Period and absolute change from
baseline in facialVASI, VES in the Extension 
Period.
Rationale: The exploratory endpoints outlined 
above are added to provide opportunity to 
evaluate the efficacy of PF-06651600 compared 
to placebo by facial-VASI and VES during the 
Dose Ranging Period and to evaluate the long 
term efficacy of PF-06651600 and efficacy of
PF-06700841 by absolute change from baseline 
in facial-VASI, VES. 

In the Schedule of Activities, visit window is 
revised for Table 3, 4, and 5. 
Rationale: Visit Window is revised to allow
greater flexibility for participant scheduling. 

In the Section 1.2.3.1 Nonclinical Safety, added 
new non-clinical safety information. 
Rationale: emerging data from Rat Fertility study 
was added.  

In the Section 1.2.3.2 Clinical Experience, 
emerging data was added demonstrating a drug 
interaction (DDI) with oral contraceptives 
containing ethinyl estradiol (EE).  Section 4.4.1 
Contraception Requirements were modified to 
include an additional barrier method of 
contraception when combined (estrogen- and 
progestogen-containing) hormonal contraception 
(oral, intravaginal, transdermal, injectable) 
associated with inhibition of ovulation is used.
Rationale: Contraception requirements revised
based on the new oral contraceptive DDI study 
to ensure patient safety. 

Section 1.2.4 Study Rationale, Section 4 Subject 
Eligibility Criteria, and Section 4.4.1 
Contraception Requirements, No contraception 
methods are required for male subjects under 




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correct minor grammatical or spelling errors.
Original 
protocol
28 August 2018
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...................................................................................................................15
LIST OF FIGURES .................................................................................................................16
APPENDICES .........................................................................................................................16
PROTOCOL SUMMARY.......................................................................................................17
SCHEDULE OF ACTIVITIES................................................................................................23
1. INTRODUCTION ...............................................................................................................48
1.1. Mechanism of Action/Indication.............................................................................48
1.2. Background and Rationale ......................................................................................48
1.2.1. Study Background ......................................................................................48
1.2.2. Non-Clinical Pharmacokinetics and Metabolism.......................................49
1.2.2.1. Non-Clinical Pharmacokinetics and Metabolism of 
PF-06651600 .....................................................................................49
1.2.2.2. Non-Clinical Pharmacokinetics and Metabolism of 
PF-06700841 .....................................................................................50
1.2.3. Safety Data..................................................................................................51
1.2.3.1. Non-Clinical Safety...................................................................51
1.2.3.2. Clinical Experience ...................................................................52
1.2.4. Study Rationale...........................................................................................62
1.2.4.2. PF-06700841 Dose Rationale for Extension Period .................66
1.2.5. Summary of Benefits and Risks .................................................................68
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................70
2.1. Study Objectives and Endpoints during Dose Ranging Period...............................70
2.2. Study Objectives and Endpoints during Extension Period......................................72
3. STUDY DESIGN.................................................................................................................74
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................77
4.1. Inclusion Criteria.....................................................................................................77
4.2. Exclusion Criteria....................................................................................................79
4.3. Randomization Criteria ...........................................................................................85
4.4. Lifestyle Requirements ...........................................................................................86
4.4.1. Contraception..............................................................................................87
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4.5. Sponsor’s Qualified Medical Personnel..................................................................89
5. STUDY TREATMENTS.....................................................................................................89
5.1. Allocation to Treatment ..........................................................................................90
5.2. Breaking the Blind ..................................................................................................90
5.3. Subject Compliance.................................................................................................90
5.4. Investigational Product Supplies.............................................................................91
5.4.1. Dosage Form(s) and Packaging..................................................................91
5.4.2. Preparation and Dispensing........................................................................91
5.5. Administration.........................................................................................................91
5.6. Investigational Product Storage ..............................................................................92
5.7. Investigational Product Accountability...................................................................93
5.7.1. Destruction of Investigational Product Supplies ........................................93
5.8. Concomitant Treatment(s).......................................................................................93
5.8.1. Narrow Band Ultraviolet B Light (nbUVB)...............................................93
5.8.2. Permitted Concomitant Medications ..........................................................94
5.8.3. Prohibited Medications and Treatments .....................................................94
5.8.4. Vaccinations ...............................................................................................95
5.8.5. Rescue Medication......................................................................................95
6. STUDY PROCEDURES .....................................................................................................95
6.1. Screening.................................................................................................................96
6.2. Dose Ranging Period...............................................................................................97
6.3. Extension Period .....................................................................................................97
6.4. Follow-up Period including End of Study...............................................................97
6.5. Subject Withdrawal/Early Termination ..................................................................97
7. ASSESSMENTS..................................................................................................................99
7.1. Pregnancy Testing...................................................................................................99
7.3. Safety Assessments ...............................................................................................101
7.3.1. Vitals Signs...............................................................................................101
7.3.2. Medical History, Physical Exam, Height, and Weight.............................102
7.3.3. Chest Radiography....................................................................................103
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7.3.4. Electrocardiogram.....................................................................................103
7.3.5. Tuberculosis Testing.................................................................................103
7.3.5.1. Interferon Gamma Release Assay (IGRA) Tuberculin Test ...103
7.3.5.2. Mantoux/Purified Protein Derivative (PPD) Tuberculin 
Skin Test..........................................................................................104
7.3.6. Special Safety Assessment .......................................................................104
7.3.6.1. Dermatological Events ............................................................104
7.3.6.2. Creatinine, Cystatin C, and estimates of Glomerular 
Filtration Rate (eGFR).....................................................................105
7.3.7. Audiometry...............................................................................................106
7.3.8. Clinical Laboratory Tests .........................................................................106
7.3.8.1. Blood Volume .........................................................................106
7.3.8.2. Laboratory Tests......................................................................106
7.4. Clinical Efficacy Assessments ..............................................................................109
7.4.1. Facial Vitiligo Area Scoring Index (Facial-VASI)—Central Read..........109
7.4.2. Vitiligo Area Scoring Index (VASI).........................................................110
7.4.3. Facial Vitiligo Area Scoring Index (Facial-VASI)-Site Assessment .......110
7.4.4. Static Investigator Global Assessment (sIGA).........................................111
7.4.5. Body Surface Area (BSA) ........................................................................111
7.4.6. Vitiligo Extent Score (VES) .....................................................................112
7.4.7. Dermoscopy..............................................................................................112
7.4.8. Target Lesion(s) Assessment....................................................................112
7.5. Columbia Suicide Severity Rating Scale (C-SSRS)..............................................113
7.6. Patient Report Outcome (PRO) Measures ............................................................113
7.6.1. Self-Assessment Vitiligo Extent Score (SA-VES)...................................113
7.6.2. Vitiligo-Specific Quality of Life (VitiQoL) and Patient Global 
Impression of Severity of Vitiligo (PGIS-V).................................................113
7.6.3. Dermatology Life Quality Index (DLQI) .................................................114
7.6.4. Hospital Anxiety and Depression Scale (HADS).....................................114
7.6.5. Patient Health Questionnaire – 8 items (PHQ-8) .....................................114
7.6.6. Patient Global Impression of Change- Vitiligo (PGIC-V) .......................114
7.6.7. EQ-5D-5L.................................................................................................114
7.6.8. Healthcare Resource Utilization (HCRU) ................................................114




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8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................122
8.2. Definitions.............................................................................................................123
8.2.1. Adverse Events.........................................................................................123
8.2.2. Abnormal Test Findings ...........................................................................123
8.2.3. Serious Adverse Events ............................................................................124
8.2.4. Adverse Reactions and Serious Adverse Reactions .................................124
8.2.5. Hospitalization..........................................................................................125
8.3. Severity Assessment..............................................................................................126
8.4. Special Situations ..................................................................................................126
8.4.1. Protocol-Specified Serious Adverse Events .............................................126
8.4.1.1. Potential Cases of Drug-Induced Liver Injury ........................126
8.4.2. Potential Cases of Decreased eGFR .........................................................128
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................129
8.4.3.1. Exposure During Pregnancy....................................................129
8.4.3.2. Exposure During Breastfeeding ..............................................131
8.4.3.3. Occupational Exposure ...........................................................131
8.4.4. Medication Errors .....................................................................................131
8.4.4.1. Medication Errors....................................................................131
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................132
9.1. Sample Size Determination...................................................................................132
9.2. Efficacy Analysis ..................................................................................................133
9.2.1. Analysis of the Primary Endpoint.............................................................133
9.2.2. Analysis of Secondary Endpoints.............................................................134
9.2.2.1. Analysis of the Key Secondary Endpoint ...............................134
9.2.2.2. Analysis of Other Secondary Endpoints .................................134
9.5. Safety Analysis during the Dose Ranging Period .................................................135
9.6. Analysis during the Extension Period ...................................................................136
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9.6.3. Safety Analysis .........................................................................................136
9.7. Interim Analysis during the Dose Ranging Period................................................137
9.8. Data Monitoring Committee .................................................................................137
9.9. Safety Adjudication Committees ..........................................................................137
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................137
11. DATA HANDLING AND RECORD KEEPING ...........................................................138
11.1. Report Forms/Data Collection Tools/Electronic Data Record............................138
11.2. Record Retention.................................................................................................139
12. ETHICS............................................................................................................................139
12.1. Institutional Review Board/Ethics Committee....................................................139
12.2. Ethical Conduct of the Study ..............................................................................140
12.3. Subject Information and Consent........................................................................140
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................141
13. DEFINITION OF END OF TRIAL.................................................................................141
13.1. End of Trial in All Participating Countries .........................................................141
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................141
15. PUBLICATION OF STUDY RESULTS........................................................................141
15.1. Communication of Results by Pfizer ..................................................................141
15.2. Publications by Investigators ..............................................................................142
16. REFERENCES ................................................................................................................144
LIST OF TABLES
Table 1.
Schedule of Activities for Screening Period and Dose Ranging Period...............23
Table 2.
Schedule of Activities for Group 1 in the Extension Period (Subjects 
Assigned to Receive PF-06700841; Open Label) ................................................29
Table 3.
Schedule of Activities for Group 2 in the Extension Period (Subjects 
Assigned to Receive Narrow Band UVB (nbUVB) Add-on Therapy; Open 
Label)....................................................................................................................33
Table 4.
Schedule of Activities for Groups 3, 4, and 5 in the Extension Period 
(Subjects Receive All Other IP Assignments [Except for nbUVB Add-on 
Therapy or PF-06700841]; Blinded Arms)...........................................................38
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Table 5.
Schedule of Activities for Group 6 in the Extension Period (Observations 
only; No IP; Open Arm) .......................................................................................42
Table 6.
Schedule of Activities for Follow-Up Period and Early Termination Visit .........45
Table 7.
Summary of Predicted Steady State Plasma PF-06651600 Pharmacokinetic 
 Parameters.......................................................................64
Table 8.
Summary of the Predicted In Vitro Average Percent Signaling Inhibition 
Based on Steady State Pharmacokinetics of PF-06651600 ..................................65
Table 9.
Summary of Predicted Steady State Total Plasma PF-06700841 
Pharmacokinetic 
 Parameters ...........................................67
LIST OF FIGURES
Figure 1.
Mean (90% CIs) Percentage Change from Baseline on Day 1 for IP-10 
mRNA Following a Single Oral Dose of PF-06651600 (SAD Period)................66
Figure 2.
Study Design Schema for Screening Period and Dose Ranging Period...............74
Figure 3.
Study Design Schema for Extension Period and Follow-up Period.....................75
APPENDICES
Appendix 1. Abbreviations....................................................................................................149
Appendix 2. Prohibited Concomitant Medications................................................................155
Appendix 4. Management of Dermatological Events............................................................159
Appendix 5. Guidelines for Subject Safety Monitoring and Discontinuation.......................160
Appendix 5.1. Monitoring......................................................................................................160
Appendix 5.2. Discontinuation ..............................................................................................160
Appendix 6. Vitiligo Extent Score (VES)..............................................................................163
Appendix 7. Columbia Suicide Severity Rating Scale (C-SSRS)27.......................................164
Appendix 8. Pruritus Numeric Rating Scale (NRS) for Potential Drug-related Rash...........169
Appendix 9. Fitzpatrick Skin Type........................................................................................170
Appendix 10. Country-Specific Requirements......................................................................171
Appendix 11. Alternative Measures During Public Emergencies .........................................174
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PROTOCOL SUMMARY
Background and Rationale
The janus kinase (JAK) family, including JAK1, JAK2, JAK3 and tyrosine-protein 
kinase 2 (TYK2), is a group of cytoplasmic tyrosine kinases that mediate signal transduction 
via interactions with Type 1 and Type 2 cytokine receptors which are critical for leukocyte 
activation, proliferation, survival and function.35,36  Upon binding of the cytokine to its 
receptor, the associated JAKs are activated, and phosphorylate each other and the receptor.  
The phosphorylated receptors serve as docking sites for the signal transducer and activator of 
the transcription (STAT) family of transcription factors.  The STATs are phosphorylated and 
subsequently translocate to the nucleus where they bind to specific gene promoters to 
activate transcription of a range of target genes.35,36
PF-06651600 is an orally bioavailable small molecule that inhibits, by irreversibly blocking 
the ATP binding site, JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma 
(TEC) kinase family (bruton’s tyrosine kinase [BTK], bone marrow-expressed kinase 
[BMX], inducible T-cell kinase [ITK], TEC, resting lymphocyte kinase [RLK/TXK]), with 
high selectivity over the other three JAK isoforms, JAK1, JAK2, and TYK2, as well as over 
the broader kinome.  PF-06651600 is currently being investigated in patients with 
rheumatoid arthritis, alopecia areata, ulcerative colitis, and Crohn’s disease and will be 
investigated in vitiligo. Considering the pathogenesis of vitiligo and mechanisms of action 
for PF-06651600, the hypothesis is to determine if PF-06651600 will have a clinically 
meaningful effect on treating active non-segmental vitiligo.
PF-06700841 is a dual TYK2/JAK1 inhibitor with a good selectivity profile over the other 
human kinases including JAK2.  TYK2/JAK1 play critical roles in interferon gamma (IFN)
signaling that regulate the signal transduction pathways triggered by several cytokines 
implicated in the pathogenesis of vitiligo.21
Study Objectives and Endpoints
Study Objectives and Endpoints during Dose Ranging Period
Primary Objectives:
Primary Endpoints:

To evaluate the efficacy of PF-06651600 
dose/dosing regimens at Week 24 in adult 
subjects with active non-segmental 
vitiligo.

Percent change from baseline in central read
facial-vitiligo area scoring index (facial-VASI) at 
Week 24.

To evaluate the safety and tolerability of
PF-06651600 over time in adult subjects 
with active non-segmental vitiligo.

Incidence of treatment-emergent adverse events (AEs) 
and serious adverse events (SAEs) up to Week 24.

Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
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Secondary Objectives:
Secondary Endpoints:
Key Secondary Objective:

To evaluate the efficacy of PF-06651600 
compared to placebo as measured by 
facial-VASI at Week 24 in adult subjects 
with active non-segmental vitiligo.
Key Secondary Endpoint:

Proportion of subjects achieving central read 
facial-VASI75 (defined as at least 75% improvement 
in central read facial-VASI from baseline) at 
Week 24.
Other Secondary Objectives:

To evaluate the efficacy of PF-06651600 
compared to placebo as measured by other 
clinical assessments over time in adult 
subjects with active non-segmental 
vitiligo.
Other Secondary Endpoints:

Proportion of subjects achieving VASI50 (defined as 
at least 50% improvement in VASI from baseline) at 
Week 24.

Percent change from baseline in VASI, central read 
and site assessment of the facial-VASI, vitiligo extent 
score (VES), and self assessment VES (SA-VES) and 
absolute change from baseline in VASI at designated 
time points (except for Week 24 for central read 
facial-VASI). 

Proportion of subjects achieving VASI50/75/90/100
(defined as at least 50%/75%/90% or 
100% improvement in VASI from baseline), central 
read and site assessment of the 
facial-VASI50/75/90/100 (defined as at least 
50%/75%/90% or 100% improvement in facial-VASI 
from baseline), and VES50/75/90/100 (defined as at 
least 50%/75%/90%/100% improvement in VES from 
baseline) at designated time points (except for 
Week 24 in VASI50 and central read facial-VASI75).

Change from baseline in vitiligo specific quality of 
life (VitiQoL) at designated time points.

Proportion of subjects achieving a static investigator 
global assessment (sIGA) 0 or 1, and at least 2-point 
improvement at Week 24.
Tertiary/Exploratory Objective(s):
Tertiary/Exploratory Endpoint(s):

To evaluate the efficacy of PF-06651600 
compared to placebo by other efficacy 
markers in adult subjects with active 
non-segmental vitiligo.

Absolute change from baseline in central read and site 
assessment of the facial-VASI and VES at designated 
time points.

Change from baseline in dermatology life quality 
index (DLQI)/EuroQol 5 dimension 5 level
(EQ-5D-5L)/healthcare resource utilization (HCRU)
at designated time points as specified in the SoA.

Facial target lesion improvement (by planimetry) of 
≥50% from baseline at Week 24 (if data allow).

Proportion of subjects achieving “very much 
improved” or “much improved” on patient global 
impression of change in vitiligo (PGIC-V).

Proportion of subjects achieving a score of 4 (a lot 
less noticeable) or 5 (no longer noticeable) on Vitiligo 




























































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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06651600 is an orally bioavailable small molecule that inhibits, by irreversibly blocking 
the ATP binding site, JAK3 and the TEC kinase family (BTK, BMX, ITK, TEC, RLK/TXK), 
with high selectivity over the other three JAK isoforms, JAK1, JAK2, and TYK2, as well as 
over the broader kinome.  PF-06651600 is currently being investigated in patients with 
rheumatoid arthritis, alopecia areata, ulcerative colitis, and Crohn’s disease and will be 
investigated in vitiligo. 
PF-06700841 is a dual inhibitor of human tyrosine-protein kinase 2 (TYK2) and Janus 
kinase 1 (JAK1) that is currently being investigated in patients with psoriasis, alopecia 
areata, ulcerative colitis, and Crohn’s disease and will be investigated in vitiligo.
1.2. Background and Rationale
The JAK family, including JAK1, JAK2, JAK3 and TYK2, is a group of cytoplasmic 
tyrosine kinases that mediate signal transduction via interactions with Type 1 and Type 2 
cytokine receptors which are critical for leukocyte activation, proliferation, survival and 
function.35,36  Upon binding of the cytokine to its receptor, the associated JAKs are activated, 
and phosphorylate each other and the receptor.  The phosphorylated receptors serve as 
docking sites for the signal transducer and activator of transcription (STAT) family of 
transcription factors.  The STATs are phosphorylated and subsequently translocate to the 
nucleus where they bind to specific gene promoters to activate transcription of a range of 
target genes.35,36
PF-06651600 potently inhibits signaling of the common-chain receptors for IL-2, IL-15, 
and IL-17, which have been implicated in the pathogenic pathways of vitiligo.2,13
Considering the pathogenesis of vitiligo and mechanisms of action for PF-06651600, the 
hypothesis is to determine if PF-06651600 will have a clinically meaningful effect on 
treating active non-segmental vitiligo.
PF-06700841 is a dual TYK2/JAK1 inhibitor with a good selectivity profile over the other 
human kinases including JAK2.  TYK2/JAK1 play critical roles in IFNsignaling that 
regulate the signal transduction pathways triggered by several cytokines implicated in the 
pathogenesis of vitiligo.21
1.2.1. Study Background
Vitiligo is an acquired hypopigmented disorder with or without autoimmune comorbidities 
including thyroid disease, alopecia areata, psoriasis, inflammatory bowel disease, type 1 
diabetes mellitus and pernicious anemia.29  The worldwide prevalence of vitiligo ranges 
between 0.5% and 2.0%.19 Lesions are depigmented completely at the initiation phase and 
pigmented orifices of hair follicles are seen at the recovering phase.  Differential diagnoses 
include Vogt-Koyanagi-Harada disease, halo nevus/nevi, malignancy-induced 
hypopigmentation (melanoma and mycosis fungoides), postinflammatory hypopigmentation, 
pityriasis alba (a minor manifestation of atopic dermatitis), senile leukoderma (age-related 


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depigmentation), chemical/drug-induced leukoderma, ataxia telangiectasia, tuberous 
sclerosis, and melasma.33 Vitiligo can be classified into two forms based on distribution 
patterns: non-segmental vitiligo (wide distribution; also known as generalized vitiligo) and 
segmental vitiligo (confined to the dermatome).6,33 Vitiligo also can be classified into two 
forms based on disease activities: active vitiligo (confetti-like lesions, trichrome lesions and 
Koebner phenomenon) and stable vitiligo (more than 30% of white hair as determined by 
dermoscopy).1,16 Since vitiligo has been given a diagnosis code (L80) by the World Health 
Organization, may result from autoimmunity, has numerous systemic associations, and 
adversely affects quality of life with significant economic burden, it is considered a serious 
medical disease.7  
The trifecta of vitiligo pathogenesis can be oxidative stress causing melanocyte damage, 
genetics affecting melanocyte growth and differentiation, and autoimmunity involving 
autoreactive cytotoxic T cells,26 although, the complex pathophysiology of vitiligo is not 
fully understood.  Stressed melanocytes may initiate the activated innate immunity via 
natural killer cells and nearby dendritic cells, followed by the activation of adaptive 
immunity.26 The presence of CD8+ T cells in close apposition to melanocytes suggests that 
the pathogenesis of vitiligo is T cell mediated although antibody-mediated pathogenesis is
also proposed.33 Recent review proposes the hypothesis that CD8+ T cells produce IFN , 
which activate the release of CXCL9/10/11 from keratinocytes, which in turn activate the 
function of CD8+ T cells via the activation of CXCR3.26 Cytokines involved in vitiligo 
include IFN, IL-2, IL-17, IL-15 and IL-4.  Of note, IL-2 and IL-15 are suggested to activate 
CD49a+/CD8+ resident memory T cells in vitiligo skin and to induce perforin and granzyme 
B in those T cells, which induce melanocyte apoptosis.2
There are currently no approved treatments specifically to treat active non-segmental vitiligo.  
Current treatment options, which are limited and may be inefficacious, include topical 
corticosteroids, topical vitamin D3, topical calcineurin inhibitors, systemic corticosteroids (to 
treat rapidly progressive active lesions), phototherapy, surgical treatments (to treat small and 
stable lesions) and camouflage.6,26,29 Recent case reports have suggested potential utility of 
JAK inhibitors in treating vitiligo. Tofacitinib a JAK inhibitor, appears to have a 
repigmentation effect on vitiligo, noting that concomitant phototherapy may be 
necessary.3,8,18,20  Ruxolitinib, a JAK1/2 inhibitor, also seems to have a similar effect.10,17,28
Considering the pathogenesis of vitiligo and mechanisms of action for PF-06651600 and 
PF-06700841, the hypothesis is to determine if PF-06651600 and PF-06700841 will have a 
clinically meaningful effect on treating active non-segmental vitiligo.
1.2.2. Non-Clinical Pharmacokinetics and Metabolism 
1.2.2.1. Non-Clinical Pharmacokinetics and Metabolism of PF-06651600
Following intravenous and oral administration of PF-06651600 to rats and dogs, absorption 
was rapid with high bioavailability in both species (approximately 85-100%).  The high oral 
bioavailability indicated high absorption from the gut, consistent with its high in-vitro 
passive permeability properties.  Plasma clearance (CL) was approximately 69 and 
13 mL/min/kg in rat and dog respectively.  Half-life was approximately 0.33 and 1.1 hour in 
rat and dog respectively.  Systemic exposures of PF-06651600 as measured by maximum 


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concentration (Cmax) and area under the concentration-time curve (AUC24) in repeat oral 
pivotal toxicology studies increased with increasing dose in rats (up to 400 mg/kg/day) and 
dogs (up to 45 mg/kg/day).  Renal excretion of parent PF-06651600 was limited in the rat 
and dog.  Biliary excretion of parent PF-06651600 was limited in the rat. 
PF-06651600 binding to plasma proteins was approximately 10 to 30% across species 
(fraction unbound values for rat, dog, and human were 0.67, 0.82 and 0.86 respectively).  
In vitro and in vivo metabolite profiling suggested that the primary clearance mechanisms for
PF-06651600 were cytochrome P450 mediated oxidation and glutathione related conjugation.  
No unique human metabolites were observed in vitro compared to metabolite profiles in rat 
and dog.  Reaction phenotyping in recombinant enzyme systems identified CYP3A4 as the 
predominant CYP450 isoform responsible for the metabolism of PF-06651600, with minor 
contributions from CYP2C19 and CYP3A5.  In addition, glutathione-S-transferase (GST) 
conjugate was formed in a time dependent manner in recombinant GST mu 1-1 and pi 1-1 
incubations. 
PF-06651600 showed a low risk of inhibition and induction of the major CYP450 enzymes 
as well as the major uridine 5’-diphospho-glucuronosyltransferase enzymes.  However, in the 
presence of nicotinamide adenine dinucleotide phosphate, PF-06651600 showed evidence of 
time-dependent inhibition of CYP3A4.  This CYP3A4 inhibition indicated a potential for 
pharmacokinetic drug interactions for which CYP3A constitutes the primary mechanism of 
clearance. 
Further details of the non-clinical pharmacokinetics and metabolism of PF-06651600 are 
provided in the current Investigator’s Brochure (IB).
1.2.2.2. Non-Clinical Pharmacokinetics and Metabolism of PF-06700841
The pharmacokinetic (PK) of PF-06700841 have been studied in rat where the compound has 
shown a plasma clearance of 31 mL/min/kg, a volume of distribution of 2.0 L/kg, and oral 
bioavailability of approximately 80-100%.  The high oral bioavailability indicated high 
absorption from the gut, consistent with its high in-vitro passive permeability properties.  Rat 
in vivo clearance was predicted within approximately 2-fold by both in vitro rat liver 
microsomes and hepatocyte intrinsic clearance highlighting the importance of CYP450 
metabolism.  Systemic exposures of PF-06700841 as measured by Cmax and AUC24 in repeat 
oral pivotal toxicology studies increased with increasing dose in rats (up to 55 mg/kg/day) 
and monkeys (up to 45 mg/kg/day).  Renal and biliary elimination of parent PF-06700841 
was limited in rat. 
Plasma protein binding of PF-06700841 was consistent across rat, monkey, and human with 
a fraction unbound (fu) of approximately 0.6-0.7.  Values of fu were lower in mouse 
(fu = 0.51) and rabbit (fu = 0.36).
Oxidative metabolites of PF-06700841 accounted for the primary routes of biotransformation 
in rat, monkey, and human consistent with CYP450 as the primary clearance route.  No 
unique human metabolites of PF-06700841 were evident compared to the safety species of 
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Safety Results
SAD Period: during the SAD period, 31 subjects had a total of 42 treatment-emergent 
adverse events (TEAE)s, 30 of which were considered to be treatment-related.  There were 
no deaths, severe adverse events (AE)s, temporary discontinuations, or dose reductions due 
to AEs reported in this period.  Two (2) subjects reported treatment-emergent serious adverse 
events (SAEs) during the SAD period (1 subject each in the PF-06651600 200 mg [furuncle]) 
and PF-06651600 400 mg [pilonidal cyst] treatment groups).  Four (4) subjects discontinued 
from the study during the SAD period (1 subject each in the placebo [erythema] and the 
PF-06651600 100 mg [rash macro papular], PF-06651600 200 mg [furuncle], and 
PF-06651600 400 mg [pilonidal cyst] treatment groups) due to AEs.
The system organ classes (SOCs) with the greatest number of subjects reporting AEs in the 
SAD period were infections and infestations (8 subjects); nervous system disorders 
(7 subjects); gastrointestinal (GI) disorders (5 subjects); musculoskeletal and connective 
tissue disorders (5 subjects); and respiratory, thoracic and mediastinal disorders (5 subjects).  
Most TEAEs reported in the SOCs of GI disorders, musculoskeletal and connective tissue 
disorders, and nervous system disorders (5 subjects in each SOC) were treatment-related.
There were generally few TEAEs in the SAD period, most of which occurred in a single 
subject, with the exception of headache and nasopharyngitis (experienced by 5 subjects each) 
and oropharyngeal pain (experienced by 4 subjects).  Most of the TEAEs were mild in 
severity except for the following AEs that were moderate in severity: 1 AE each in the 
PF-06651600 5 mg (oropharyngeal pain), 20 mg (musculoskeletal pain), and 200 mg 
(subcutaneous abscess) treatment groups; 2 AEs in the placebo group (dry skin and limb 
injury); 3 AEs in the PF-06651600 400 mg treatment group (nasopharyngitis, pilonidal cyst, 
and headache), and 5 AEs in the PF-06651600 100 mg treatment group (abdominal pain, 
arthralgia, rash maculopapular, and 2 AEs of headache).
MAD Period: during the MAD period, 35 subjects had a total of 90 TEAEs, 75 of which 
were considered to be treatment-related.  The treatment groups with the most AEs were the 
PF-06651600 400 mg QD (39 AEs in 13 subjects), 200 mg BID (16 AEs in 5 subjects), and 
100 mg BID treatment groups (14 AEs in 4 subjects).  There were no deaths, temporary 
discontinuations, or dose reductions due to AEs reported in this period.  One (1) subject who 
received PF-06651600 400 mg QD during the MAD period reported an SAE (varicella).  
Two (2) subjects experienced severe AEs during the MAD period (1 subject each in the 
PF-06651600 400 mg QD [varicella] and PF-06651600 200 mg BID [rash macro papular] 
treatment groups.  Two (2) subjects discontinued from the study during the MAD period 
(1 subject each in the PF-06651600 400 mg QD [herpes zoster] and PF-06651600 
200 mg BID [rash macro-papular] treatment groups) due to AEs.
The SOCs with the greatest number of subjects reporting AEs in the MAD period were skin 
and subcutaneous tissue disorders (21 subjects); GI disorders (18 subjects); nervous system 
disorders (12 subjects); musculoskeletal and connective tissue disorders (6 subjects); and 
respiratory, thoracic, and mediastinal disorders (5 subjects).  Most TEAEs reported in the 
SOCs of skin and subcutaneous tissue disorders (20 subjects), GI disorders (17 subjects), and 








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comparison of individual and dose normalized geometric mean Cmax and AUCtau values.  The 
geometric mean value for the accumulation ratio (Rac) ranged from 1.0 to 1.8 for the QD 
dosing and was 1.7 for the 100 mg BID dosing.  This ratio compares AUCtau for multiple 
dose administration to AUCtau for single dose administration, and assesses the magnitude of 
accumulation with multiple dose administration.  Similar Rac ratios were observed for Cmax
(RacCmax), which ranged from 0.9 to 1.4 for QD dosing and was 1.0 for 100 mg BID dosing.  
The steady state accumulation ratio (Rss) compares AUCtau for multiple dose administration 
to AUCinf for single dose administration, and assesses the linearity in PK exposure from a 
single dose to steady state.  Geometric mean Rss values were consistently ≥1, ranging from 
1.0 to 1.8, suggesting that there may be a greater than dose proportional increase in 
PF-06651600 exposure with multiple dose administration.  However, based on Rac and 
RacCmax, the increase in exposure after 14 days of multiple dosing is less than 2-fold for any 
of the dosing regimens studied.  Steady state generally appears to have been reached by 
Day 4 for the QD regimens and Day 6 for the BID regimens based on similar median trough 
(predose) concentrations on Days 6, 8, 10, 12 and 14.
Urinary recovery of PF-06651600 was low, with approximately <8% of the dose recovered 
unchanged in urine on Day 14 across all doses (geometric mean amount of drug excreted 
from time zero to time tau, the dosing interval [Aetau]% of 4.1% to 7.0%).  Renal clearance 
ranged from 42.9 mL/min to 63.1 mL/min.
The relative bioavailability (B7981003) of 50 mg PF-06651600 tablets was compared to 
50 mg oral suspension.  The ratio (90% confidence interval [CI]) of adjusted geometric mean 
was 93.4% (87.8, 100) for AUCinf and 90.4% (72.2, 113) for Cmax under fasted conditions.  
When the 50 mg tablets were administered under fed conditions, Tmax was slightly delayed 
with a median value of 1.0 hours, compared to a median Tmax 0.5 hours under fasted 
conditions.  For the 50 mg tablets fed vs. fasted, the ratio of adjusted geometric means for 
AUCinf and Cmax was 102% (95.2, 109) and 61.5% (48.5, 77.8), respectively.
On Day 1 following the first morning oral dose of PF-06651600 200 mg under fasted 
conditions to healthy Japanese, PF-06651600 absorption was rapid with a median Tmax of 
0.525 hours and a range of 0.500-1.00 hours. Overall, exposures as measured by AUCtau
based on geometric mean were 3779 ng•hr/mL and for Cmax of 1803 ng/mL on Day 1 after a 
single dose. Mean t½ was 1.69 hours and it was calculated based on a 24–hour sampling. 
Trough (predose) concentrations on Days 4, 6, 8 and 10 for all subjects were below the lower 
limit of quantification (LLOQ) (<1.00 ng/mL).
Following multiple oral dosing on Day 10, AUCtau increased slightly while Cmax was similar 
to Day 1. The geometric mean values for AUCtau and Cmax were 4983 ng•hr/mL and 
1790 ng/mL, respectively. Median Tmax was similar to Day 1 with a value of 0.500 hours 
with no range for Day 10. Following the attainment of Cmax, concentrations appeared to 
decline in monophasic fashion.  A short mean t½ was observed with an estimate of 1.8 hours. 
Based on AUCtau calculation, mean apparent total body clearance of the drug from plasma 
(CL/F) was 40.1 L/hr and mean apparent volume of distribution during terminal phase after 
non-intravenous administration (Vz/F) was 103 L.


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Plasma PF–06651600 accumulation was 1.3–fold for AUCtau (observed Rac) and 0.99–fold 
for Cmax (observed accumulation ratio for Cmax [RacCmax]). Geometric mean Rss was 
1.3 (close to 1), suggesting linear increases in PF-06651600 exposure with multiple-dose 
administration. 
Variability in plasma PF–06651600 exposure on Day 1 and Day 10 based on geometric 
percent coefficient of variation (%CV), ranged from 35% to 43% for Cmax and from 23% to 
25% for AUCtau. 
Urinary recovery of PF-06651600 was low, with <7% of the dose recovered unchanged in 
urine on Day 10 (geometric mean percent of dose recovered unchanged in urine up to 
24 hours [Aetau%] of 6.89%).  Renal clearance was approximately 46.1 mL/min.
1.2.3.2.2. Clinical Experience with PF-06700841
1.2.3.2.2.1. First-in-Human (B7931001) Safety Data 
The FIH study was a Phase 1, randomized, double-blind, third party open, 
placebo-controlled, single and multiple dose escalation, parallel group study in healthy adult 
subjects and subjects with plaque psoriasis (PsO), with a relative bioavailability and food 
effect assessment of a tablet formulation of PF-06700841 in healthy adult subjects.  In the 
completed first-in-human study (B7931001), 41 healthy volunteers were exposed to single 
doses and 26 of the 41 subjects received multiple daily doses of PF-06700841 over 10 days; a 
small cohort of plaque PsO patients (n=21) were treated once daily with PF-06700841 for 
28 days at 30 mg and 100 mg doses.
An additional healthy volunteer cohort was included to support the evaluation of the relative 
BA of a tablet formulation of PF-06700841, and assessment of a high fat meal on tablet BA.  
Twelve healthy subjects participated in this BA assessment, and received single doses of 
open label PF-06700841 in a 3-way cross over design (PF-0670841 tablet fasted, 
PF-06700841 solution/suspension fasted, and PF-06700841 tablet under fed 
conditions).PF-06700841 was generally safe and well tolerated in the Phase 1 clinical study 
B7931001.
The most commonly reported all causality TEAEs across active subjects in both SAD and 
MAD cohorts were increased blood creatinine, and decreased neutrophil count. In the SAD 
period, 1 subject in the PF-06700841 100 mg group had serum creatinine (Scr) values 
meeting the criteria for high levels (>1.3 X ULN). In the MAD period, 4 subjects (1, 2, and 
1 subjects in the PF-06700841 10 mg QD, 100 mg QD, and 50 mg BID groups, respectively)
had Scr values meeting the criteria for high levels. No subjects in the psoriasis period had 
SCr values meeting the criteria for high levels. In the SAD period, 3 subjects (1 subject each 
in the PF-06700841 1 mg, 200 mg, and placebo group) had abnormal low neutrophil counts 
(<0.8 X LLN). In the MAD period, 14 subjects (1, 3, 3, 5, and 2 subjects in the 
PF-06700841 10 mg QD, 100 mg QD, 50 mg BID, 175 mg QD, and placebo group, 
respectively) had abnormal low neutrophil counts. In the psoriasis period, 6 subjects (1 and 
5 subjects in the PF-06700841 30 mg and 100 mg QD groups, respectively) had abnormal 
low neutrophil counts. All laboratory abnormalities reported as AEs were mild in severity, 






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entire dose range. Mean t½ was 3.8-7.5 hours with a trend towards longer t½ at the higher 
doses, probably due to concentrations remaining above the lower limit of quantification 
(LLOQ) for a longer time as the dose increased.  The mean CL/F was 10.9-28.3 L/hr and the 
mean Vz/F was 102.4-210.5 L.  Variability in PF-06700841 exposure based on 
geometric %CV ranged from 31%-65% for AUCinf and 21%-92% for Cmax.
On Day 10 of multiple-dose administration, PF-06700841 was absorbed rapidly with median 
Tmax at or before 1.5 hours postdose across the entire range of doses from a total daily dose of 
10 mg up to 175 mg.  Plasma Cmax and AUCtau both appeared to increase proportionally with 
dose from 10 mg QD to 100 mg QD with a trend towards greater than proportional increase 
from 100 mg to 175 mg QD.  As would be expected, dose normalized Cmax for 50 mg BID is 
slightly higher than that for 100 mg QD while dose normalized AUCtau is consistent between 
the two dosing regimens.  Mean terminal t½ ranged from 4.9 to 10.7 hours.  Steady state 
generally appeared to have been reached by Day 8 of QD or BID dosing.  Urinary recovery 
of PF-06700841 was low, with less than 16% of the dose recovered unchanged.
Following multiple-dose administration in subjects with PsO, PF-06700841 was absorbed 
rapidly with median Tmax of 1 to 2 hours post dose.  Mean terminal t½ was 16 hours in the 
30 mg group and 6 hours in the 100 mg group.  The mean t½ value in the 30 mg group 
included a reported t½ value of 87.5 hours for one subject with an anomalous data point at 
216 hours postdose.  All other subjects in the dose group had concentrations below the 
LLOQ after 24 hours and t½ values of 6.48 hours or less.  The subject in the 30 mg group 
with the highest Cmax and AUCtau values was not the same subject with the anomalous 
87.5 hour t½ value.  CL/F and Vz/F were 30.30 L/hr and 245.4 L for the 30 mg dose, 
respectively, and were 13.04 L/hr and 109.6 L for the 100 mg dose, respectively.  Variability 
in PF-06700841 exposure based on geometric %CV ranged from 43% to 103% for AUCtau
and 13% to 43% for Cmax.
Relative BA of 100 mg PF-06700841 tablets compared to 100 mg oral suspension was 
96.18% for AUCinf and 94.28% for Cmax.  Both of the 90% CIs for the ratio were within the 
80%-125% equivalence interval. When the 100 mg tablets were administered under fed 
conditions, Tmax was delayed with a median value of 4.0 hours, compared to 0.5 hours under 
fasted conditions.  For 100 mg tablets fed versus fasted, the ratio (90% CI) of adjusted 
geometric means for AUCinf and Cmax was 82.33% (73.45%, 92.29%) and 64.25% (55.98%, 
73.75%), respectively.
Following single oral dose of PF-06700841 100 mg under fasted conditions in Japanese 
subjects, absorption was rapid with a median Tmax of 1 hour and a range of 0.5-2 hours on 
Day 1. Geometric mean AUCinf was 8725 ng•hr/mL and Cmax was 1035 ng/mL. Mean 
terminal t½ was 5.7 hours based on a 24-hour sampling.
On Day 10 following multiple oral dosing, median Tmax was 0.76 hours with a range of 
0.5-4.0 hours. Both AUCtau and Cmax increased slightly compared to Day 1, with geometric 
mean values of 9888 ng•hr/mL and 1114 ng/mL, respectively. Mean terminal t½ was 
8.9 hours. Steady-state generally appeared to have been achieved by Day 6. Urinary 
recovery of PF-06700841 was low, with less than 16% of the dose recovered unchanged.














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1.2.5. Summary of Benefits and Risks
There are currently no approved treatments specifically to treat active non-segmental vitiligo. 
Recent case reports have suggested potential utility of JAK inhibitors in treating vitiligo as 
detailed in Section 1.2.1.  
Both PF-06651600 and PF-06700841 inhibit signal transduction pathways triggered by 
several cytokines implicated in the pathogenesis of vitiligo. Considering the mechanisms of 
action for PF-06651600 and PF-06700841 and the vitiligo pathogenesis, both IPs are 
expected to have a clinically meaningful effect for the treatment of active non-segmental 
vitiligo. 
The dose rationales for PF-06651600 and PF-06700841 are detailed in Sections 1.2.4.1 and 
1.2.4.2, respectively.
PF-06651600 and PF-06700841 are generally safe and well tolerated as supported by the 
totality of safety data to date. Overall, the safety profile observed during the Phase 1
program for PF-06651600 appears to be acceptable at dosages up to 200 mg administered 
orally QD.  The safety profile observed during the Phase 1 program for PF-06700841 appears 
to be acceptable at dosages up to 175 mg administered orally QD. 
In the ongoing Phase 2a proof-of-concept Study B7931005 in adult patients with alopecia 
areata (AA), preliminary data showed that both PF-06651600 and PF-06700841 met its 
primary endpoint of improvement in severity of alopecia tool (SALT) 30 score relative to 
placebo at Week 24.  PF-06651600 and PF-06700841 appeared generally safe and well 
tolerated as suggested by adverse event (AE) number and profile. Both PF-06651600 and 
PF-06700841 had a favorable benefit: risk profile and provided meaningful clinical benefit in 
AA, another dermatological disease with similar underlying pathogenesis and psychological 
burden as vitiligo.47,48
In the Study B7981019, events requiring review, including opportunistic infections, 
cardiovascular, and malignancy events will be externally evaluated using the same 
adjudication committee as in the ongoing Phase 2b AA Study B7981015 as detailed in 
Section 9.9. 
Based on the current clinical and nonclinical experience with PF-06651600, PF-06700841, 
and other information from other JAK inhibitors (eg, Xeljanz® (tofacitinib), Jakafi®
(ruxolitinib), baricitinib, GLPG0634, and VX-509), the potential risks for PF-06651600 and 
PF-06700841 include: (1) viral reactivation; (2) serious infection and opportunistic 
infections; (3) malignancy and lymphoproliferative disorders; (4) decreased lymphocyte 
counts; (5) change in neutrophil counts; (6) decreased platelet count; (7) alterations in the 
lipid profile; (8) dermatologic effects (rash/acne); (9) interaction with other medicinal 
products and other forms of interaction; (10) fertility, pregnancy, and lactation.




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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Study Objectives and Endpoints during Dose Ranging Period
Primary Objectives:
Primary Endpoints:

To evaluate the efficacy of PF-06651600 
dose/dosing regimens at Week 24 in adult 
subjects with active non-segmental 
vitiligo.

Percent change from baseline in central read 
facial-vitiligo area scoring index (facial-VASI) at 
Week 24.

To evaluate the safety and tolerability of 
PF-06651600 over time in adult subjects 
with active non-segmental vitiligo.

Incidence of treatment-emergent adverse events (AEs) 
and serious adverse events (SAEs) up to Week 24.

Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
profile, and liver function tests (LFTs) up to Week 24.
Secondary Objectives:
Secondary Endpoints:
Key Secondary Objective:

To evaluate the efficacy of PF-06651600 
compared to placebo as measured by 
facial-VASI at Week 24 in adult subjects 
with active non-segmental vitiligo.
Key Secondary Endpoint:

Proportion of subjects achieving central read 
facial-VASI 75 (defined as at least 75% improvement 
in central read facial-VASI from baseline) at 
Week 24.
Other Secondary Objectives:

To evaluate the efficacy of PF-06651600 
compared to placebo as measured by other 
clinical assessments over time in adult 
subjects with active non-segmental 
vitiligo.
Other Secondary Endpoints:

Proportion of subjects achieving VASI50 (defined as 
at least 50% improvement in VASI from baseline) at 
Week 24.

Percent change from baseline in VASI, central read 
and site assessment of the facial-VASI, vitiligo extent 
score (VES), and self assessment -VES (SA-VES) and 
absolute change from baseline in VASI at designated 
time points (except for Week 24 for central read 
facial-VASI).

Proportion of subjects achieving VASI50/75/90/100 
(defined as at least 50%/75%/90% or 100% 
improvement in VASI from baseline), central read 
and site assessment of the facial-VASI50/75/90/100 
(defined as at least 50%/75%/90% or 100% 
improvement in facial VASI from baseline), and 
VES50/75/90/100 (defined as at least 
50%/75%/90%/100% improvement in VES from 
baseline) at designated time points (except for 
Week 24 in VASI50 and central read facial-VASI75).

Change from baseline in vitiligo specific quality of 
life (VitiQoL) at designated time points.

Proportion of subjects achieving a static investigator 
global assessment (sIGA) 0 or 1, and at least 2-point 
improvement at Week 24.
















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2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
3. Male or female subjects between 18-65 years of age, inclusive, at time of informed 
consent. 
4. Female subjects of childbearing potential and at risk for pregnancy must agree to use 
one method of contraception (per Section 4.4.1) throughout the study and for at least 
28 days after the last dose of assigned treatment.
Female subjects of non-childbearing potential must meet at least 1 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; status may be confirmed with a serum follicle-stimulating 
hormone (FSH) level confirming the postmenopausal state;
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. 
Note: For all subjects assigned to Group 1 in the Extension Period, please refer to 
Section 4.4.1. 
5.
Must meet the following active non-segmental vitiligo criteria at the Screening Visit
and the Baseline Visit:
a.
Have a clinical diagnosis of non-segmental vitiligo for at least 3 months; and
b. Body surface area (BSA) involvement 4% - 50% excluding involvements at 
palms of the hands, dorsal aspect of fingers and thumbs including 
metacarpophalangeal joints, soles of the feet, or dorsal aspect of the feet; and
c.
BSA ≥0.25% involvement on the face excluding involvement at vermilion 
(confirmed by photographs at Screening Visit); and
d. Subjects should have at least one active lesion defined as one of the following:
(i) New/extending lesion(s) in the past 3 months (confirmed by photographs or 
medical record); 
(ii) Confetti-like lesion(s); 
(iii) Trichrome lesion(s); 


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(iv) Koebner phenomenon/ phenomena [excluding Type 1 (history based 
isomorphic reaction)];
e.
Coexistence of halo nevus/nevi (also known as Sutton nevus/ nevi) is permitted.
6. If receiving concomitant medications for any reason other than vitiligo, must be on a 
stable regimen, which is defined as not starting a new drug or changing dosage within 
7 days or 5 half-lives (whichever is longer) prior to Day 1.  Subject must be willing to 
stay on a stable regimen during the duration of the study (Section 5.8.2). 
7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun 
lamps or other ultraviolet light sources other than provided/requested by the study 
team during the study (Section 4.4 Lifestyle Requirements).
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. 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.
2. Other acute or chronic medical 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 or sponsor, would make the subject inappropriate for entry into this 
study.
3. Any psychiatric condition including recent or active suicidal ideation or behavior that
meets any of the following criteria: 

Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale 
(C-SSRS) (Section 7.5). 

Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for 
events that occurred in the past 5 years) to any of the suicidal behavior items of 
the C-SSRS. 

Any lifetime history of serious or recurrent suicidal behavior. 

Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) 
(Section 7.6.5) total score ≥15. 


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
The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 

In the opinion of the investigator, exclusion is required. 
4. Subjects considered in imminent need for surgery (for example in the next 6 months)
or with elective surgery scheduled to occur during the study. 
5. Subjects that have other types of vitiligo (including but not limited to segmental 
vitiligo). Note: Mixed vitiligo is permitted.
6. Currently have active forms of other hypopigmentation (including but not limited to 
Vogt-Koyanagi-Harada disease, malignancy-induced hypopigmentation [melanoma 
and mycosis fungoides], post-inflammatory hypopigmentation, pityriasis alba [minor 
manifestation of atopic dermatitis], senile leukoderma [age-related depigmentation], 
chemical/drug-induced leukoderma, ataxia telangiectasia, tuberous sclerosis, 
melasma, and congenital hypopigmentation disorders including piebaldism, 
Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti, 
dyschromatosis symmetrica hereditaria, xeroderma pigmentosum, and nevus 
depigmentosus).  Note: Coexistence of halo nevus/nevi (also known as Sutton 
nevus/nevi) is permitted.
7. Currently have active forms of inflammatory skin disease(s) or evidence of skin 
conditions (including but not limited to morphea, discoid lupus, leprosy, syphilis, 
psoriasis, seborrheic dermatitis) at the time of the Screening or Day 1 Visit that in the 
opinion of the investigator would interfere with evaluation of vitiligo or response to 
treatment.
8. Have received any of the following treatment regiments specified in the timeframes 
outlined below: 
At any time:

Use of permanent depigmentation treatment for vitiligo and/or other types of 
pigmentation disorders (eg, monobenzone or phenol).
Within 6 months of Day 1:

Any cell-depleting agents including but not limited to rituximab: within 
6 months of Day 1, or 5 half-lives (if known), or until lymphocyte count 
returns to normal, whichever is longer.
Within 12 weeks of Day 1:

Use of oral JAK inhibitors.


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
Other biologics: within 12 weeks of Day 1 or 5 half-lives (if known), 
whichever is longer.
Within 8 weeks of Day 1:

Systemic treatments that could affect vitiligo within 8 weeks of Day 1 or 
within 5 half-lives (if known), whichever is longer.

Use of oral immune suppressants (eg, cyclosporine A, azathioprine, 
methotrexate [MTX], sulfasalazine, systemic corticosteroids, 
mycophenolate-mofetil,) within 8 weeks of Day 1 or within 5 half-lives (if 
known), whichever is longer.

Intralesional steroid injection within 8 weeks of Day 1 or within 5 half-lives 
(if known), whichever is longer.

Participation in other studies involving investigational drug(s) within 8 weeks 
of Day 1 or within 5 half-lives (if known), whichever is longer and/or during 
study participation.
Note: Any investigational or experimental therapy taken or procedure performed 
for vitiligo and other diseases including but not limited to rheumatoid arthritis, 
psoriasis, alopecia areata, thyroid disease, allergic rhinitis, or atopic dermatitis 
within the previous 1 year should be carefully evaluated.  Subjects cannot 
participate in studies of other investigational or experimental therapies or 
procedures at any time during their participation in this study.
Within 6 weeks of Day 1:

Live or attenuated live vaccine.
Within 4 weeks of Day 1:

Ultra-Violet B (UVB) phototherapy, Psoralen Ultra-Violet A therapy, or other 
phototherapy.
Within 2 weeks of Day 1:

Topical treatments (including JAK inhibitors) that could affect vitiligo 
(eg, corticosteroids, vitamin D3, and calcineurin inhibitor).
Within 1 week of Day 1:

Herbal medications with unknown properties or known beneficial effects for 
vitiligo.


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9. Pregnant female subjects; breastfeeding female subjects; and female subjects of 
childbearing potential who are unwilling or unable to use one method of 
contraception as outlined in this protocol for the duration of the study and for at least 
28 days after the last dose of investigational product. 
10. Have current or recent history of clinically significant severe, progressive, or 
uncontrolled renal (including but not limited to active renal disease or recent kidney 
stones), hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, 
cardiovascular, psychiatric, immunologic/rheumatologic or neurologic disease; or 
have any other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration, or interfere with the interpretation of study 
results; history of severe allergic or anaphylactoid reaction to kinase inhibitors; or in 
the opinion of the investigator, the subject is inappropriate for entry into this study, or 
unwilling/unable to comply with Section 6 Study Procedures and Section 4.4
Lifestyle Requirements.
11. Have hearing loss with progression over the previous 5 years, sudden hearing loss, or 
middle or inner ear disease such as otitis media, cholesteatoma, Meniere’s disease, 
labyrinthitis, or other auditory condition that is considered current, fluctuating or
progressive.
12. Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV)
related lymphoproliferative disorder, history of lymphoma, history of leukemia, or 
signs and symptoms suggestive of current lymphatic or lymphoid disease.
13. Have a history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster.
14. Have a history of systemic infection requiring hospitalization, parenteral 
antimicrobial therapy, or as otherwise judged clinically significant by the investigator 
within 6 months prior to Day 1.
15. Have active acute or chronic skin infection requiring treatment with systemic 
antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks 
prior to Day 1, or superficial skin infections within 2 weeks prior to Day 1. 
NOTE: patients may be rescreened after the infection resolves.
16. Have a history of alcohol or substance abuse within 6 months prior to Day 1 that in 
the opinion of the investigator will preclude participation in the study or protocol 
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17. ANY of the following conditions at screening:
a.
12-lead electrocardiogram (ECG) that demonstrates:

Clinically significant abnormalities requiring treatment (eg, acute myocardial 
infarction, serious tachy- or brady-arrhythmias) or indicating serious 
underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson-White 
syndrome); 

Confirmed QTcF prolongation (>450 milliseconds).
b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of 
Torsades de Pointes; 
c.
Use of concomitant medications that prolong the QT interval.
18. Have a known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
19. Abnormal findings on the screening chest radiographs (eg, chest X-ray) including, but 
not limited to, presence of TB, general infections, heart failure, or malignancy.  Chest 
radiographs examination may be performed up to 12 weeks prior to Day 1.  
Documentation of the official reading must be available in the source documentation. 
20. Have any malignancies or have a history of malignancies with the exception of 
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the 
skin or cervical carcinoma in situ.
21. Have undergone significant trauma or major surgery within 1 month of the first dose 
of IP.
22. Require treatment with prohibited concomitant medication(s) (Section 5.8.3 and
Appendix 2) or have received a prohibited concomitant medication within 7 days or 
5 half-lives (whichever is longer) prior to Day 1.
23. History of human immunodeficiency virus (HIV) or positive HIV serology at 
screening. 
24. Infected with hepatitis B or hepatitis C viruses.  For Hepatitis B, all subjects will 
undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core 
Antibody (HBcAb) during Screening.  Subjects who are HBsAg positive are not 
eligible for the study.  Subjects who are HBsAg negative and HBcAb positive will be 
reflex tested for Hepatitis B Surface Antibody (HBsAb) and if HBsAb is positive, 
may be enrolled in the study; if HBsAb is negative, the subject is not eligible for the 
study.  For Hepatitis C, all subjects will undergo testing for Hepatitis C antibody 
(HCVAb) during Screening.  Subjects who are HCVAb positive are not eligible for 
the study. Note: For Japan, Korea and Taiwan, please refer to Appendix 10.


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25. Infected with Mycobacterium tuberculosis (TB) as defined by the following:
a.
A positive Interferon Gamma Release Assay (IGRA) test or positive
Mantoux/Purified Protein Derivative (PPD) tuberculin skin test performed at or 
within the 12 weeks prior to Day 1 is exclusionary; a negative test is required for 
eligibility.  It is strongly recommended that subjects with a history of Bacille 
Calmette Guérin (BCG) vaccination be tested with the IGRA test since the 
Mantoux/PPD tuberculin skin test may be positive due to vaccination.  See 
Section 7.3.5 for requirements for Mantoux/PPD tuberculin skin testing.  The 
following are acceptable IGRA assays: QuantiFERON® - TB Gold test (QFT-G), 
QuantiFERON® - TB Gold In-Tube test (QFT-GIT) and T-SPOT®.

If the results of the IGRA are indeterminate, the test may be repeated, and if a 
negative result is obtained, enrollment may proceed.  A positive test on repeat 
is exclusionary.

Subjects with repeat indeterminate IGRA results may be enrolled after 
consultation with pulmonary or infectious disease specialist who determines 
that the risk of infection is low (ie, subject would be acceptable for 
immunosuppressant treatment without additional action).

Subjects who test positive for IGRA test (including borderline T-SPOT 
result), but in the opinion of the principal investigator (PI) are at low risk of 
TB infection may be referred to pulmonary or infectious disease specialist for 
consultation and may have the IGRA test repeated once.  Subjects will be 
eligible if the repeat test is negative before the randomization.
b. Chest radiograph taken at screening (or performed and documented within 
3 months prior to Day 1) with changes suggestive of active TB infection.
c.
A subject who has been treated or is currently being treated for active or latent TB 
infection is to be excluded.
d. A history of either untreated or inadequately treated latent or active TB infection
is to be excluded.
26. Have galactosemia (galactose-1-phosphate-uridylyltransferase or 
UDP-galactose-4-epimerase or galactokinase deficiency; Fanconi Bickel syndrome), 
a congenital lactase deficiency or glucose-galactose malabsorption.
27. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
28. ANY of the following abnormalities in clinical laboratory tests at screening, as 
assessed by the study-specific laboratory and confirmed by a single repeat, if deemed 
necessary:

Absolute neutrophil count of <2.5 x 109/L (<2500/mm3);


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
Hemoglobin <10.0 g/dL or hematocrit <30%; 

Platelet count below the lower limit of normal (LLN) at Screening;

Absolute lymphocyte count of <0.8 x 109 /L (<800/mm3); 

Serum creatinine > upper limit of normal (ULN) or eGFR <60 ml/min/1.73m2
based on the age appropriate calculation;

Enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
values >2 times the ULN; 

Total bilirubin ≥1.5 times the ULN; subjects with a history of Gilbert's syndrome 
may have a direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin is≤ULN;

Creatine kinase (CK) >3 times the ULN and positive urine myoglobin;

Glycosylated hemoglobin A1c (HbA1c) >10%; Subjects whose diabetes mellitus 
is poorly controlled should be excluded; 

In the opinion of the investigator or Pfizer (or designee), have any uncontrolled 
clinically significant laboratory abnormality that would affect interpretation of 
study data or the subject’s participation in the study.
4.3. Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.  This study plans to enroll a total of approximately 330 subjects (expected to provide 
approximately 260 completers).  Eligible subjects will be randomly assigned to a treatment 
group through the interactive response technology (IRT) system stratified by subject skin 
type, and geographical locations. 
Subjects will be randomized to 1 of 5 active treatment groups or placebo in the ratio of 
4:4:4:3:3:4 approximately. An induction dose of 200 mg QD of PF-06651600 for 4 weeks 
followed by maintenance dosing of 50 mg QD of PF-06651600 for 20 weeks (n=60), an 
induction dose of 100 mg QD of PF-06651600 for 4 weeks followed by maintenance dosing 
of 50 mg QD of PF-06651600 for 20 weeks (n=60), a dose of 50 mg QD of PF-06651600 for 
24 weeks (n=60), a dose of 30 mg QD of PF-06651600 for 24 weeks (n=45), a dose of 
10 mg QD of PF-06651600 for 24 weeks (n=45), and matching placebo for 24 weeks (n=60) 
will be investigated during the 24 week Dose Ranging Period.




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
Agree to use the sunscreen (provided by the sponsor) during the study conduct. 

New tattoo that may interfere with vitiligo assessment will be prohibited during the 
study conduct.

For subjects who undergo color application (camouflage), or other procedures to their 
body surface/eyebrow/eyelash that may interfere with vitiligo assessment, the 
procedures should be avoided at least one week prior to the scheduled clinical 
assessment visits.  This will facilitate the consistency of vitiligo clinical assessment.

Agree not to use makeup prior to the scheduled clinical assessment visits to facilitate 
the accuracy and consistency of vitiligo assessment.

Agree to avoid strenuous exercise during the study, especially within one week prior 
to the scheduled study visits and maintain adequate hydration, if possible.
4.4.1. Contraception
In this study, fertile male subjects and female subjects who are of childbearing potential will 
receive PF-06651600 (and PF-06700841 in the Extension Period).  PF-06700841 has been 
associated with demonstrated teratogenicity/fetotoxicity in animals (more details in IB). 
For PF-06651600 or placebo: 
No contraception methods are required for male subjects under PF-06651600 or placebo in 
the study.
Female subjects who are, in the opinion of the investigator, sexually active and at risk for 
pregnancy with their partner(s) must agree to use 1 method of highly effective contraception 
(as defined below) throughout the study and for at least 28 days after the last dose of 
investigational product.  
For PF-06700841: 
The risk of drug exposure to a sexual partner through ejaculate, vaginal secretion, or saliva 
from a subject on maximum oral doses of PF-06700841 at Cmax is below pharmacologically 
relevant levels, and unlikely to present a significant risk of adverse effects on embryofetal 
development. However, all sexually active male subjects in Group 1 who are assigned to 
receive PF-06700841 during the Extension Period 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.
In addition to male condom use, a highly effective method of contraception (as defined 
below) should be used in women of child bearing potential (WOCBP) partners of male 
participants to prevent any potential for fertilization by sperm throughout the study and for at 
least 28 days after the last dose of investigational product.  


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Female subjects in Group 1 who are assigned to receive PF-06700841 during the Extension 
Period and in the opinion of the investigator are sexually active and at risk for pregnancy 
with their partner(s) must agree to use 1 method of highly effective contraception (as defined 
below) throughout the Extension Period and for at least 28 days after the last dose of 
PF-06700841.  
In addition to a highly effective method of contraception use, male partner(s) of female 
participants in Group 1 must agree to use 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. If the female subject under PF-06700841 chooses sexual 
abstinence, male condom use is not applicable.
The investigator or his or her designee, in consultation with the subject, will confirm that the 
subject has selected appropriate method(s) of contraception for the individual subject and 
his/her partner(s) from the list of permitted contraception methods (see below) and will 
confirm that the subject has been instructed in their consistent and correct use.  At time 
points indicated in the Schedule of Activities, the investigator or designee will inform the 
subject of the need to use appropriate method(s) of contraception consistently and correctly 
and document the conversation, and the subject’s affirmation, in the subject’s chart.  In 
addition, the investigator or designee will instruct the subject to call immediately if 1 or both
of the selected contraception methods is discontinued or if pregnancy is known or suspected 
in the subject or partner. 
Highly Effective Methods :
1. Oral, injectable, or implantable progestogen-only hormone contraception associated 
with inhibition of ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion or bilateral tubal ligation.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed.  If not, an additional highly effective method of contraception 
should be used.  The spermatogenesis cycle is approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation used in 
combination with a barrier method. 


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Acceptable barrier methods include:

Male or female condom with or without spermicide.

Cervical cap, diaphragm, or sponge with spermicide.
Male condom and female condoms should not be used together (due to risk of failure 
with friction).
7. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
Additionally, contraceptive use should be consistent with local regulations or guidance 
regarding the use of contraceptive methods for those participating in clinical trials.
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 study portal. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study. The contact
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33). 


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For this study, the investigational product(s) are PF-06651600 and PF-06700841
(PF-06700841 for Extension Period only).  Phototherapy will be used for subjects who will 
be allocated to nbUVB add-on therapy during Extension Period.
5.1. Allocation to Treatment
Allocation of subjects to treatment groups will occur through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number. The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject number, randomization number, and DU 
or container number assigned. The confirmation report must be stored in the site’s files. 
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
5.2. Breaking the Blind 
The study will be double blind (sponsor, subject and investigator blinded) during the Dose 
Ranging Period. During the Extension Period, the group 1 (PF-06700841 arm) and group 2 
(PF-06651600 with nbUVB arm) will be open label while the other 3 arms (group 3, 4 and 5) 
will be double blind. Group 6 is for observation only. No IP will be administered. 
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes should be 
broken only in exceptional circumstances when knowledge of the actual treatment code is 
absolutely essential for further management of the subject.  Investigators are encouraged to 
discuss with a member of the study team if they believe that unblinding is necessary.  
However, discussion with a member of the study team in advance of unblinding is not 
required. When the blinding code is broken, the reason must be fully documented and 
entered on the case report form (CRF).
Details of unblinding plan for possible interim analysis will be specified in interim analysis 
plan.
5.3. Subject Compliance
For self-administration of PF-06651600 or PF-06700841 at home, subject compliance will be 
verified by the accounting of investigational product at each visit.  When investigational 
product is administered at the study site, it will be administered under the supervision of 
study personnel.


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Compliance of the investigational product will be monitored by delegated site personnel by 
the accounting of unused medication returned by the subject at the study visits.  Compliance 
will be documented on the source document.  If compliance is <80% or >120%, the 
investigator or designee is to counsel the subject and ensure steps are taken to improve 
compliance.  Subjects interrupting investigational product for more than 4 consecutive days 
or for a total of more than 7 days between visits are to be discussed with the sponsor for 
possible withdrawal from the study.
5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
Blinded PF-06651600 tablets and matching placebos will be provided as tablets for oral 
administration.  PF-06700841 will be provided as tablets for oral administration.  The 
designation “PF-06651600-15” and “PF-06700841-15” may appear on labeling and indicates 
a salt.  The PF-06651600 10 mg and 50 mg tablets and their matching placebos will be 
supplied in blisters and labeled according to local regulatory requirements.  The 
PF-06700841 5 mg and 25 mg tablets will be supplied in bottles and labeled according to 
local regulatory requirements.  Subjects will receive blinded labeled supplies for 
PF-06651600 throughout the study including the Extension Period.  PF-06700841 supplies 
will be open label.
5.4.2. Preparation and Dispensing
The investigational product (IP) will be dispensed using an IRT drug management system at 
each visit according to Schedule of Activities.  A qualified staff member will dispense the 
investigational product via unique container numbers on the bottles or blister labels provided, 
in quantities appropriate for the study visit schedule.  The subject/caregiver should be 
instructed to maintain the product in bottles or blisters provided throughout the course of 
dosing and return the bottles or blisters to the site at the next study visit. 
5.5. Administration
Subjects will receive IP as outpatients.  PF-06651600 tablets and matching placebo for oral 
administration will be dispensed in blisters.  PF-06700841 tablets for oral administration will
be dispensed in bottles.  Subjects will be provided clear dosing instructions.
Sites will be trained on how subjects should take tablets at home through an IP manual and/or 
other vehicle(s).  Sites are responsible for communicating this information and site staff 
should review the dosing instructions with subjects at every study visit.
Subjects should take the medication orally once daily; Subjects should swallow the tablets 
with ambient temperature water to a total volume of approximately 240 mL (2.4 DL or 
1 cup); Subjects will swallow the investigational product whole, and will not manipulate or 
chew the medication prior to swallowing; Subjects will be encouraged to take the 
medication after breakfast whenever possible even though IP may be taken with or
without food; however, for study visit days, subjects are to be instructed to refrain from 
dosing at home, and are to take the dose in the clinic (from the containers being returned to 
the site [ie, dispensed at the previous study visit]).


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If a dose is missed and the interval to the next dose is less than 8 hours, the missed dose 
should not be administered.
Study treatment may be temporarily withheld (or adjusted) for a maximum of 4 consecutive 
days at the discretion of the investigator.  Subjects interrupting investigational product for 
more than 4 consecutive days or 7 days between visits are to be discussed with the sponsor 
for possible withdrawal from the study.
5.6. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels. 
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order. 
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion.  Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.


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Site staff will instruct subjects on the proper storage requirements for take home 
investigational products. 
5.7. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be
accounted for using a drug accountability form/record. 
All IPs must be returned to the investigator by the subject at every applicable visit and at the 
end of the trial.
5.7.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
For all blisters/bottles returned to the investigator by the subject, the investigator will 
maintain the returned supply until destruction is authorized.  Pfizer will provide instructions 
as to the disposition of any unused investigational product.
5.8. Concomitant Treatment(s)
Medications that are taken in the Screening period (after informed consent is obtained and 
before the first dose of IP) will be documented as prior medications.  Medications taken after 
the first dose of IP has been administered will be documented as concomitant medications.  
All concomitant medications taken during the study must be recorded in study records with 
indication, daily dose, and start and stop dates of administration.  Subjects will be queried 
about concomitant medication (including topical medications and treatments, 
over-the-counter and prescription medications and treatments, and vaccinations) at each 
study visit.  Any new concomitant medications or dose changes to current concomitant 
medications should be evaluated for potential new or worsening adverse events.
The start date, stop date, and indication for all therapies will be recorded on the CRF.
5.8.1. Narrow Band Ultraviolet B Light (nbUVB)
The use of narrow band ultraviolet b light (nbUVB) phototherapy may be an important 
component in the Extension Period to enhance melanocyte growth and differentiation.  In the 
Extension Period, subjects who have signed a consent form for the nbUVB will have a 
chance to receive an induction dose of 200 mg QD plus standardized nbUVB add-on therapy
for 4 weeks followed by maintenance dosing of 50 mg QD plus standardized nbUVB add-on 
therapy for 20 weeks.  This arm will be an unblinded arm since the other 4 arms in the 
Extension Period will not use nbUVB.  Sun exposure is prohibited during nbUVB 
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The administration of nbUVB phototherapy will follow the Vitiligo Working Group 
phototherapy recommendations (Appendix 3)23 except that nbUVB phototherapy will be 
conducted twice a week during the study instead of three times a week. 
Subjects who have <10% improvement in percent change in VASI at Extension Week 12 
from baseline at Week 24 Dose Ranging Period will be discontinued from the treatment and 
enter Follow-up Period.
5.8.2. Permitted Concomitant Medications
Acetaminophen may be used intermittently (not to exceed 1 g/day).  For the purposes of this 
protocol, dietary supplements are defined as vitamins, minerals, and purified food substances 
with pharmaceutical properties.  Vitamins, minerals and purified food substances are allowed 
in amounts not known to be associated with adverse effects (such as hypervitaminosis).
A subject who is receiving metformin as concomitant medication must allow at least two 
hours to elapse after taking the medication and before taking investigational product.
A subject who is receiving a permitted concomitant medication for any reason must be on a 
locally-approved medication and dose for the treated indication, and this must be 
documented in the CRF.  Subjects are not allowed any other investigational drugs or 
treatments during the study. 
Subjects should refrain from starting new or changing doses of permitted prescription or 
non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives 
(whichever is longer) prior to Day 1 and throughout the study, unless otherwise noted below.
Subjects will be provided a sunscreen at the Baseline Visit.  Subjects will use the sunscreen 
Day 1 through to the End of Study Visit as needed.  If a subject has a history of intolerability 
or currently does not tolerate the sunscreen or if the product is unavailable, the investigator 
should contact the Pfizer clinician or designee for approval to use an alternative topical 
sunscreen; The approved alternative sunscreen should be documented in study records.
Subjects should report any changes to permitted medications during the study to the 
investigator as soon as they occur.  Medication changes must be documented in the subject’s 
record and CRF.
Unless a prohibited medication or treatment, subjects may be administered any other 
medications necessary for the treatment of concomitant medical disorders as deemed 
necessary by the treating physician.  Following Day 1, addition of concomitant medications 
or any change in the dosage should be limited to those considered medically essential. 
5.8.3. Prohibited Medications and Treatments
Subjects will abstain from all concomitant medications as described in the Inclusion and 
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Subjects should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications. 
A subject who is receiving simvastatin as concomitant medication should be switched at 
least 7 days prior to baseline to an alternative statin drug.  Treatment with 
simvastatin-containing products should not be initiated during participation in this study. 
All medications and treatments that could affect vitiligo must be discontinued.  Subjects 
must also avoid prolonged exposure to the sun and avoid the use of tanning booths, sun 
lamps or other ultraviolet light sources other than provided/requested by the study team 
during the study.
Herbals supplements are only allowed on a case-by-case basis; please contact the Pfizer staff.  
Herbal medications with unknown properties or known beneficial effects for vitiligo or that 
are known to have an effect on drug metabolism (eg, St. John’s Wort) must be discontinued 
at least 1 week or 5 half-lives (whichever is longer) before the first dose of investigational 
product. 
Restrictions on certain vaccinations are described in Section 5.8.4. 
5.8.4. Vaccinations
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to the first dose of IP, during the study, and for 6 weeks after the last 
dose of investigational product.  Similarly, current routine household contact with individuals 
who have been vaccinated with live vaccine components should be avoided during treatment 
and for 6 weeks following completion of treatment. 
Such vaccines include but are not limited to: FluMist® (intranasal influenza vaccine), 
attenuated rotavirus vaccine, varicella (chickenpox) vaccine, attenuated typhoid fever 
vaccine, oral polio vaccine, MMR (measles, mumps, rubella) vaccine and vaccinia 
(smallpox) vaccine.  Following vaccination with live component vaccines, the virus may be 
shed in bodily fluids, including stool, and there is a potential risk that the virus may be 
transmitted.
5.8.5. Rescue Medication
Since currently there are no approved treatments in vitiligo (other than phototherapy), no 
rescue therapy will be mandated by the sponsor. Subjects requiring rescue medication during 
the Dose Ranging Period or Extension Period will be discontinued from IP (PF-06651600 or 
PF-06700841 or placebo) and will enter the Follow-up Period. Subjects requiring rescue 
medication during the Follow-up Period should also complete the Follow-up Period. 
6. STUDY PROCEDURES 
Refer to the Schedule of Activity for a detailed list of study procedures as they should be 
conducted at each respective visit.  Visit windows are based on Day 1 visit.




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For screening procedures, see Schedule of Activities and Section 7.
6.2. Dose Ranging Period
For treatment period procedures, see Schedule of Activities Table 1 and Section 7.
6.3. Extension Period
For subjects in Group 1 (who are assigned to receive PF-06700841 in the Extension Period)
procedures, see Schedule of Activities Table 2 and Section 7.
For subjects in Group 2 (who are assigned to receive narrow band UVB (nbUVB) add-on 
therapy in the Extension Period procedures, see Schedule of Activities Table 3 and Section 7.
For subjects in Groups 3, 4, and 5 (who receive all other assignments [except for nbUVB
add-on therapy or PF-06700841] in the Extension Period) procedures, see Schedule of 
Activities Table 4 and Section 7.
For subjects in Group 6 (observation only) procedures, see Schedule of Activities Table 5
and Section 7. 
6.4. Follow-up Period including End of Study
Follow-up Visit 1 will occur 4 weeks after the Extension Week 24 (ExW24).  End of Study 
Visit will occur 4 weeks after the FU Visit 1 or Early Termination (ET) Visit.  For early
terminated subjects, End of Study (EOS) Visit will occur 4 weeks (with a visit window of 
+7 days based on the ET Visit) after the Early Termination (ET) Visit and no FU1 Visit will 
be performed.
The procedures scheduled for ET Visit will be performed on the last day the subject takes the 
investigational product or as soon as possible thereafter.
For follow-up and end of study procedures, see Schedule of Activities Table 6 and Section 7.
6.5. Subject Withdrawal/Early Termination
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site. 
Subjects who are requested to discontinue study treatment from the Dose Ranging Period or 
Extension Period (except for Group 6) will enter into the Follow-up Period with their End 
of Study Visit occurring 4 weeks after the ET Visit. The procedures scheduled for ET 
Visit will be performed on the last day the subject takes the investigational product or as 
soon as possible thereafter. Subjects in Group 6 who requested to discontinue study from the 
Extension Period will have the End of Study Visit occurring 4 weeks after the last visit. No 
follow up visit will be performed.


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See Appendix 5 for guidelines on subject safety monitoring and discontinuation.  The ET 
Visit only applies to subjects who are randomized, received at least one dose of IP, and then 
are prematurely withdrawn from the study treatment.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return all unused investigational 
product(s), request that the subject return for a final visit, if applicable, and follow up with 
the subject regarding any unresolved adverse events (AEs).
Withdrawal of consent:
Subjects who request to discontinue receipt of study treatment from the Treatment Period or 
Extension Period will enter the Follow-up Period with their EOS visit occurring 4 weeks
after the ET Visit and to be followed for protocol specified follow-up procedures.  The 
procedures scheduled for ET Visit will be performed on the last day the subject takes the 
investigational product or as soon as possible thereafter.  The only exception to this is when a 
subject specifically withdraws consent for any further contact with him or her or persons 
previously authorized by the subject to provide this information. 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 post treatment study follow-up, and entered on 
the appropriate CRF page.  In the event that vital status (whether the subject is alive or dead)
is being measured, publicly available information should be used to determine vital status 
only as appropriately directed in accordance with local law.
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.
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.  Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter.  All attempts should be documented in the subject’s medical records. If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death.  If the investigator’s use of a third-party representative to assist 
in the follow-up portion of the study has been included in the subject’s informed consent, 
then the investigator may use a sponsor-retained third-party representative to assist site staff 
with obtaining the subject’s contact information or other public vital status data necessary to 


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complete the follow-up portion of the study.  The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information.  If, after all attempts, the subject remains lost to follow-up, then 
the last-known-alive date as determined by the investigator should be reported and 
documented in the subject’s medical records.
Subjects who withdraw from the study may be replaced at the discretion of the investigator 
upon consultation with the sponsor. 
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible.  The 
study team will be informed of these incidents in a timely manner.
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. Pregnancy Testing
Pregnancy tests are required to be done (if applicable) as specified in the Schedule of 
Activities. 
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at 
least 25 mIU/mL and must be performed by a certified laboratory.  For female subjects of 
childbearing potential, 2 negative pregnancy tests are required before receiving study 
treatment(s) (1 negative pregnancy test at screening and 1 at the baseline visit immediately 
before study treatment administration).  Following a negative pregnancy test result at 
screening, appropriate contraception must be commenced and the second negative pregnancy 
test result will then be required at the baseline visit before the subject may receive the study 
treatment.  In the absence of regular menstrual bleeding, the study candidate should have 
used 1 form of contraception for at least 1 month before the second pregnancy test.  
Pregnancy tests will also be repeated at every applicable visit and at the end of the study to 
confirm that the subject has not become pregnant during the study.  Pregnancy tests will also 
be done whenever 1 menstrual cycle is missed during the active treatment period and when 
potential pregnancy is otherwise suspected, and may be repeated if requested by institutional 
review boards (IRBs)/ethics committees (ECs) or if required by local regulations.  In the case 
of a positive confirmed pregnancy, the subject will be withdrawn from administration of 
investigational product but may remain in the study for follow up. 






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Subjects should be seated in a chair, back supported, and arms bared (free of restrictions such 
as rolled-up sleeves, etc.) and supported at heart level.  Measurements should be taken on the 
same arm at each visit (preferably non-dominant). Subjects should refrain from smoking or 
ingesting caffeine during the 30 minutes preceding the measurements.  Measurements should 
begin after at least 5 minutes of rest. 
Pulse should be measured at approximately the same time as BP for a minimum of 
30 seconds.  When the timing of BP and pulse (heart) rate measurements coincides with a 
blood collection or other study procedure, BP and pulse (heart) rate should be obtained first.
7.3.2. Medical History, Physical Exam, Height, and Weight
Complete vitiligo disease history includes collection of details of vitiligo at Screening: 
background, vitiligo history, vitiligo diagnosis, the use of topical treatments, systemic 
treatments and other treatments for vitiligo (up to 2 years, if possible).  Medical history, in 
addition to vitiligo history, including history of drug (up to 2 years, if possible), alcohol, 
tobacco use, auditory, skin rash, skin infection, and any dermal abnormalities that may 
predispose to infection will be collected at Screening and Baseline (if applicable).  Smoking 
status and average weekly alcohol consumption (units/week) will also be collected.
Height and weight will be measured without the subject wearing shoes.  Height (inches or 
centimeters) and weight (lbs or kgs) will be measured and recorded in the source document at 
the Baseline Visit. 
Complete physical examinations must be performed by the investigator, sub-investigator or a 
qualified health professional per local guidelines.  Complete physical examinations consist of 
assessments of general appearance; skin; head, eyes, ears, nose and throat (HEENT); mouth, 
heart; lungs; breast (optional); abdomen; external genitalia (optional); extremities; neurologic
function, back, and lymph nodes.  In addition, dermatological full body exam must be 
performed by the investigator, sub-investigator or a qualified health professional per local 
guidelines.  Dermatological examinations may include visual inspection of the breasts and 
external genitalia.
Targeted physical examinations must be performed by the investigator, sub-investigator or a 
qualified health professional per local guidelines and should include skin, heart, lung, 
neurologic function, and abdomen and examination of body systems where there are 
symptom complaints by the subject. 
Subjects with clinically meaningful changes from baseline in neurologic signs or symptoms 
should be referred to a neurologist to undergo a formal neurologic evaluation.
Complete and Targeted physical examinations are performed at various time points, see 
Schedules of Activities.


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7.3.3. Chest Radiography
Chest X-ray (posterior-anterior and lateral views are recommended, however local guidelines 
should be followed) or other appropriate diagnostic image (ie, computed tomography [CT] or 
magnetic resonance imaging [MRI]) with no evidence of abnormalities including but not 
limited to current, active TB or previous inactive TB, general infections, heart failure or 
malignancy taken at Screening or within 12 weeks prior to Study Day 1 and read by a 
qualified radiologist.  Documentation of the official reading must be located and available in 
the source documentation.
7.3.4. Electrocardiogram
Single 12-lead ECGs should be collected at times specified in the Schedule of Activities. 
All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position and prior to any blood collection. 
The baseline ECG values will serve as each subject’s baseline values.  To ensure safety of 
the subjects, a qualified medical personnel at the investigator site will make comparisons to 
baseline measurements.  A paper or digital copy of the ECG should be filed in the subject’s 
chart and must be available to the sponsor upon request.  Any clinically significant changes 
will be recorded and evaluated further, as clinically warranted.  In some cases, it may be 
appropriate to repeat abnormal ECGs to rule out improper lead placement as contributing to 
the ECG abnormality. 
7.3.5. Tuberculosis Testing
Subjects could be screened for TB using either test listed below. 
7.3.5.1. Interferon Gamma Release Assay (IGRA) Tuberculin Test
Subjects may be screened for TB using an IGRA per local guidelines.  Interferon gamma 
release assay will be tested during screening or within 12 weeks prior to Day 1.  The 
following are acceptable IGRA assays: QuantiFERON®-TB Gold test (QFT-G), 
QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT® TB test.  Site personnel 
should follow the processing and analyses steps based on the assay chosen.  Ensure 
incubation steps are followed as appropriate.
An IGRA is preferred for subjects with a prior BCG vaccination, but may be used for any 
subject.  Documentation of IGRA product used and the test result must be in the subject’s 
source documentation.
If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result 
is obtained, enrollment may proceed.  A positive test on repeat is exclusionary. 
Subjects with repeat indeterminate IGRA results may be enrolled after consultation with 
pulmonary or infectious disease specialist that determines low risk of infection (ie, subject 
would be acceptable for immunosuppressant (eg, anti-TNF) treatment without additional 
action).


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Subjects who test positive for IGRA test (including borderline T-SPOT result), but in the 
opinion of the PI are at low risk of TB infection may be referred to pulmonary or infectious 
disease specialist for consultation and potential IGRA test repeated once.  Subjects will be 
eligible if the repeat test is negative before the randomization.
Refer to lab manual for any additional processing information and shipping instructions.
7.3.5.2. Mantoux/Purified Protein Derivative (PPD) Tuberculin Skin Test
Subjects can be TB screened using the Mantoux/PPD Tuberculin Skin Test.  Mantoux/PPD 
testing can also be performed if there are indeterminate QFT-G test results.  Subjects must 
have a Mantoux/PPD tuberculin skin test administered and then evaluated by a health care
professional 48 to 72 hours later.  A positive Mantoux/PPD tuberculin skin test is 
exclusionary.
7.3.6. Special Safety Assessment
7.3.6.1. Dermatological Events
All subjects will have dermatological full body exam (s) per SOA.  Skin lesions will be
evaluated and managed as defined in the National Cancer Institute Common Toxicity Criteria 
for Adverse Events v 4.0) (Appendix 4). 
7.3.6.1.1. Herpetiform Rash 
For any occurrence of a suspected herpetiform rash (eg, herpes zoster and herpes simplex), 
specimens for viral DNA analysis will be obtained: A swab of the affected area will be 
collected for confirmation; a blood sample for viral surveillance will be collected for the 
analysis of viral load. Details for these collections will be provided in the laboratory manual.
7.3.6.1.2. Drug-Related Rash
All potential drug-related reports of rash will be followed up until resolution or clinically 
stable or in agreement with the sponsor. 
All events of rash should be treated according to International and local guidelines for the 
treatment of rash, eg, where appropriate, topical corticosteroids and/or agents such as 
antibiotics or antivirals could be prescribed. 
All subjects reporting an unexplained skin rash should undergo a formal comprehensive 
dermatologic evaluation.  A 4 mm punch biopsy will be taken unless there is a clear, 
non-drug related etiology (eg, infection, pre-existing condition) or other clinical rationale 
(eg, if the rash is present on the face it may not be appropriate to take a biopsy) or subject 
refuse to have biopsy performed.  The biopsy will be sent to the local laboratory for 
histological investigation of the rash in order to gain insight into potential etiology of the 
rash.  Note: For herpetiform rash, no biopsy is required.  Please see Section 7.3.6.1.1. 


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In addition to a biopsy of suspected drug-related rash, a swab (for microbiological 
assessment) of the affected area will also be taken for culture and sensitivity to assess (at the 
local laboratory) for any bacterial, fungal, or viral pathogens, if applicable.  A blood sample 
for viral surveillance will be collected (and sent to the central laboratory) for the analysis of 
viral load including but not limited to cytomegalovirus (CMV), EBV, herpes simplex virus 
type 1 (HSV1), herpes simplex virus type 2 (HSV2), and varicella zoster virus (VZV), if 
applicable.
Subjects reporting potential drug-related rash should assess itch on a 10-point numeric rating 
scale (NRS) provided by Pfizer where 0 is no itching and 10 is worst possible itching
(Appendix 8).  The investigator will enter this assessment into the data collection tool. 
Investigators will complete a questionnaire (provided by the study team) and take appropriate 
photographs of the rash.
All de-identified biopsy results, culture results, photographs, and any additional relevant test 
results will be forwarded to Pfizer (or designee) for review within 30 days of receipt by the 
investigator.
An independent dermatologist contracted by Pfizer may review all relevant data and 
summarize the data at the end of the study.
7.3.6.2. Creatinine, Cystatin C, and estimates of Glomerular Filtration Rate (eGFR)
Serum creatinine is the best known standard test for monitoring renal function.  However, 
serum creatinine based estimates of glomerular filtration rate (eGFR) may be affected by 
factors other than renal function, including chronic and acute illness.  Serum cystatin C is a 
test that can be used either as an adjunct to or a replacement for serum creatinine.  The most 
reliable estimates of GFR use both test results.12
Serum cystatin C is a low molecular weight protein that is used as an alternative to serum 
creatinine for monitoring of renal function.  It seems to correlate more closely with GFR than 
serum creatinine concentration and may be a more sensitive detector of early renal 
dysfunction.4,24 While use of cystatin C has been limited, its independence of demographic 
factors (eg, race) has made it an interesting means of determining changes in renal function 
in clinical settings and it is included in the 2012 Kidney Disease: Improving Global 
Outcomes (KDIGO) guidelines.  Estimated GFR may be calculated via the 2012 Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, or 
creatinine-Cystatin C equations.14
Serum creatinine will be measured as part of serum chemistry at times specified in the 
Schedule of Activities section of the protocol.  Creatinine elevations above the ULN will be 
followed until resolution or baseline.  Serum creatinine based eGFR will be calculated.  
Serum cystatin C will be measured and cystatin C based eGFR will be calculated at times 
specified in the Schedule of Activities section of the protocol. 


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The eGFR will be calculated using the 2 sets of equations developed by the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI), which utilize serum creatinine (SCr) and
serum Cystatin C (S Cystatin C) respectively.34
7.3.7. Audiometry
All subjects will have audiometry assessment at times specified in the Schedule of 
Activities.  Audiometry assessment taken at Screening or within 8 weeks prior to Day 1 must 
have results available prior to Day 1.  In addition to audiogram, information including 
auditory medical history and additional examinations (ie, otoscopic exam) will be collected.  
For subjects that terminate early from the study, efforts must be made to complete the 
audiometry testing and obtain the results.
When possible, the subject should have the audiogram performed at the same evaluation 
center during the study. 
At subsequent visits, audiograms will be performed; based upon results, additional 
audiometry assessments may be required and performed by qualified medical personnel 
based on local guideline or equivalent. 
If there is a clinically-meaningful, treatment-related decline in hearing from baseline, the 
subject will be followed up off treatment with appropriate testing at regular intervals, until 
hearing returns to baseline or is determined to be clinically stable. Treatment-relatedness (or 
causality) will be assessed by the investigator as described in Section 8.1.5.
The information from the audiogram will be entered into the data collection tool.
Any de-identified audiogram results/reports and any additional relevant test results (if 
applicable) will be requested to be forwarded to Pfizer (and/or designee) at any time during 
the study.
7.3.8. Clinical Laboratory Tests
7.3.8.1. Blood Volume
Further details regarding the collection, processing, storage, and shipping of the blood 
samples will be provided in the lab manual.
7.3.8.2. Laboratory Tests
The following laboratory tests will be performed at time points identified in the Schedule of 
Activities.  Unscheduled clinical labs may be obtained at any time during the study to assess 
any perceived safety concerns at the investigator’s discretion.
Sample collection, labeling, storage, and shipping information can be found in the laboratory 
manual.  All laboratory tests with clinically important changes from baseline identified after 
administration of investigational product will be followed until the value stabilizes.


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
Subjects must abstain from all food and drink (except water and non-investigational 
product s) for an 8-hour overnight fast prior to fasting lipid profile panel collection 
according to Schedule of Activities.  All other labs 
 
do not require fasting.
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Scalp, neck, eyebrows, eyelashes, and vermilion will be excluded from this calculation, 
although total VASI assessment includes all of these regions.
Details of the central read process, including the information flow will be described in a 
separate charter/exploratory analysis plan. 
7.4.2. Vitiligo Area Scoring Index (VASI) 
The total body VASI will be assessed by the Investigator. The total body VASI will be 
calculated using a formula that includes contribution from all body regions (possible range, 
0-100) with a modified method described by Hamzavi et al:9
VASI =     Ʃ         [Hand Units] X [Depigmentation]
                  Six (6) Different Body Sites
Percent of total body surface area (BSA) is determined by hand units. One hand unit, which 
encompasses the palm plus the volar surface of all the digits, is approximately 1% of the total 
body surface area and is used as a guide to estimate the baseline percentage of vitiligo 
involvement of each body region. 
The body will be divided into 6 separate and mutually exclusive regions: face/neck, hands, 
upper extremities (excluding hands), trunk, lower extremities (excluding the feet), and feet.  
The axillary regions are included with the upper extremities, while the buttocks and inguinal 
regions are included with the lower extremities.  Genital area is included in trunk.  Face and 
neck lesions will be measured in this study.  
The extent of depigmentation is expressed by the following percentages: 0, 10%, 25%, 50%, 
75%, 90%, or 100%.  At 100% depigmentation, no pigment is present; at 90%, specks of 
pigment are present; at 75%, the depigmented exceeded the pigmented area; at 50%, the 
depigmented and pigmented areas are equal; at 25%, the pigmented area exceeded the 
depigmented area; and at 10%, only specks of depigmentation are present. 
7.4.3. Facial Vitiligo Area Scoring Index (Facial-VASI)-Site Assessment
The site assessed facial-VASI will be assessed by the Investigator. The site assessment of 
the facial-VASI is calculated using a formula that is similar to facial-VASI central read.  It 
includes contribution from face (possible range, 0.00-4.00).  Scalp, neck, eyebrows, 
eyelashes, and vermilion will be excluded from this calculation, although total VASI 
assessment includes all of these regions.
Facial VASI =              [Digit Units] X [Depigmentation] X0.1
The volar surface of one digit (the subject’s thumb) is approximately 0.1% of the total body 
surface area and was used as a guide to estimate the baseline percentage of vitiligo 
involvement of face. 


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The extent of depigmentation is expressed by the following percentages: 0, 10%, 25%, 50%, 
75%, 90%, or 100%.  At 100% depigmentation, no pigment is present; at 90%, specks of 
pigment are present; at 75%, the depigmented exceeded the pigmented area; at 50%, the 
depigmented and pigmented areas are equal; at 25%, the pigmented area exceeded the 
depigmented area; and at 10%, only specks of depigmentation are present. 
7.4.4. Static Investigator Global Assessment (sIGA)
Static Investigator Global Assessment (sIGA) Score
Score
Short descriptor
Detailed descriptor
0
Clear

No signs of loss of pigmentation with natural light or with 
Woods lamp examination.
1
Almost clear

Faint, barely detectable loss of pigmentation mainly located 
on dorsal hands, feet, bony prominences, and/or limited 
areas.

Approximately 90% pigmentation within lesions.

No or rare signs of Koebner phenomenon, confetti-like or 
trichrome lesions may be present.
2
Mild vitiligo

Mild loss of pigmentation mainly located on dorsal hands, 
feet, bony prominences, and/or limited areas. 

Approximately 75% pigmentation within lesions.

Few signs of Koebner phenomenon, confetti-like or 
trichrome lesions may be present.
3
Moderate vitiligo

Moderate loss of pigmentation affecting several areas of the 
body with large patches.

Approximately 50% pigmentation within lesions. 

Moderate number of signs of Koebner phenomenon, 
confetti-like or trichrome lesions may be present.
4
Severe vitiligo

Extensive loss of pigmentation affecting most areas of the 
body.

Approximately 25% or less pigmentation within lesions. 

Many signs of Koebner phenomenon, confetti-like or 
trichrome lesions affecting several areas of the body may be 
present.
7.4.5. Body Surface Area (BSA) 
The number of hand units of skin afflicted with vitiligo in a body region can be used to 
determine the extent (%) to which a body region is involved with vitiligo.  When measuring, 
the hand unit refers to the size of each individual subject’s palm plus the volar surface of all 
the digits in a closed position. Rule of 9 is used to estimate BSA (Head/neck 9%; Upper 
extremities excluding hands 14%; Hands 4%; trunk including genital area 33%; Lower 
extremities excluding feet 36%; Feet 4%).


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7.4.6. Vitiligo Extent Score (VES) 
Vitiligo Extent Score is a measure to express the overall vitiligo involvement of the body 
(extent).31 Clinical illustrations for 19 separate body areas that reflect different degrees of 
involvement (1, 5, 10, 25, 50, and 75% depigmentation) are chosen to represent the subject’s 
skin lesions to get the total extent of the disease (Appendix 6).  VES is a sum of all surface 
measurement that is similar to VASI.
7.4.7. Dermoscopy
Dermoscopy will be performed per SOA. At least 2 different anatomical regions based on 
VES will be selected on Screening. At least two fields (possibly peripheral and central) from 
the largest lesion in the selected anatomical region will be examined to determine if white 
hair is present in less than 30% of hair in the depigmented lesion. Number of fields with less 
than 30% of white hair will be recorded. The same chosen lesions will be assessed per SOA.
The same dermoscopy should be used throughout the study.
7.4.8. Target Lesion(s) Assessment
One isolated and completed stable lesion (if applicable) will be identified as the stable target 
lesion on Day 1. Photographs of the lesion will be obtained (according to the separately 
provided Photography Instructions) at various time points as per SOA (Section 7.7).  The
extent of depigmentation of the target lesion is expressed by the following percentages: 
0, 10%, 25%, 50%, 75%, 90%, or 100%.  At 100% depigmentation, no pigment is present; at 
90%, specks of pigment are present; at 75%, the depigmented exceeds the pigmented area; at 
50%, the depigmented and pigmented areas are equal; at 25%, the pigmented area exceeded 
the depigmented area; and at 10%, only specks of depigmentation are present. The same 
target lesion will be assessed per SOA. Note: No depigmentation (0) may be achieved during 
the study but should not be observed on Day 1.
In case of mixed Vitiligo, one isolated segmental vitiligo lesion (if applicable) will be 
identified as the segmental target lesion on Day 1. Photographs of the lesion will be obtained 
(according to the separately provided Photography Instructions) at various time points as per 
Schedule of Activities (Section 7.7).  The extent of depigmentation of the target lesion is 
expressed by the following percentages: 0, 10%, 25%, 50%, 75%, 90%, or 100%. At 
100% depigmentation, no pigment is present; at 90%, specks of pigment are present; at 
75%, the depigmented exceeds the pigmented area; at 50%, the depigmented and pigmented 
areas are equal; at 25%, the pigmented area exceeded the depigmented area; and at 10%, only 
specks of depigmentation are present. The same target lesion will be assessed per SOA. 
Note: No depigmentation (0) may be achieved during the study but should not be observed 
on Day 1.
Target lesion assessment for active vitiligo lesion is not required. Photographs of active 
lesion, stable lesion, and segmental vitiligo lesion (if applicable) will be obtained according 
to SOA (Section 7.7).


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7.5. Columbia Suicide Severity Rating Scale (C-SSRS)
Columbia Suicide Severity Rating Scale (C-SSRS) is a validated tool to evaluate suicidal 
ideation and behavior (Appendix 6). 
At Screening Visit and Baseline Visit, if there are “yes” answers on items 4, 5 in the past 
year or on any question in the suicidal behavior section of the C-SSRS in the past 5 years, the 
subject will not be included in the study. 
At any post-baseline visits during Dosing Ranging Period or Extension Period, if there are 
“yes” answers on items 4, 5 or on any question in the suicidal behavior section of the 
C-SSRS, the subject will be discontinued from the IP and referred to a mental health 
professional for appropriate evaluation and treatment.  If the subject cannot be seen by a 
mental health professional within 24 hours, then the subject should be sent to a local 
emergency room for psychiatric assessment.
7.6. Patient Report Outcome (PRO) Measures
Every effort should be made to have the subject complete all patient reported outcome (PRO) 
questionnaires before any other evaluations.  All PROs should be completed in the order 
specified in as following: SA-VES, VitiQoL, DLQI, HADS, PHQ-8, PGIC-V, EQ-5D-5L,
HCRU and VNS, at those visits where they are to be administered except for Screening Visit 
and Baseline Visit. All of the PROs are administered as electronic version on a tablet with 
the exception of the VNS which will be administered as a paper version.
7.6.1. Self-Assessment Vitiligo Extent Score (SA-VES)
The Self-Assessment Vitiligo Extent Score (SA-VES) is a validated patient report outcome 
measurement instrument to provide information about disease extent.  SA-VES should be 
completed as per Schedule of Activities. 
7.6.2. Vitiligo-Specific Quality of Life (VitiQoL) and Patient Global Impression of 
Severity of Vitiligo (PGIS-V)
The Vitiligo-Specific Quality of Life Instrument (VitiQoL) is a reliable and validated vitiligo 
disease-specific HRQoL instrument which measures concepts relevant to vitiligo subjects.  
The VitiQoL is a 15-item PRO measure which measures concepts of symptoms, daily 
activities, leisure activities, work, personal relationships and treatment.  Responses range 
from “not at all” (scored 0) to “most of the time” (scored 6) and gives a minimum and 
maximum score from 0-90, with higher scores representing greater burden.  A minimally 
important difference has not yet been established for the questionnaire.  The VitiQoL should 
be completed as per Schedule of Activities.
The Patient Global Impression of Severity of Vitiligo (PGIS-V) is 1-item within the VitiQoL 
questionnaire which asks the subject to determine how severe they feel their skin condition is 
at that point in time on a 7-point Likert response from “no skin involvement” to “most severe 
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7.6.3. Dermatology Life Quality Index (DLQI)
The DLQI is a general dermatology questionnaire that consists of 10 items that assess subject 
health-related quality of life (daily activities, personal relationships, symptoms and feelings, 
leisure, work and school, and treatment).  The DLQI is a psychometrically valid and reliable 
instrument that has been translated into several languages, and the DLQI total scores have 
been shown to be responsive to change.  The minimal clinically important difference for the 
DLQI has been estimated as a 2 to 5 point change from baseline.  The DLQI should be 
completed as per Schedule of Activities.
7.6.4. Hospital Anxiety and Depression Scale (HADS)
The HADS is a 14-item PRO measure used to detect states of anxiety and depression over the 
past week.  Items are rated on a 4-point severity scale.  The HADS produces two scales, one 
for anxiety (HADS–A) and one for depression (HADS–D), differentiating the two states.  
Scores of greater than or equal to 11 on either scale indicate a definitive case.  The HADS 
should be completed as per Schedule of Activities.
7.6.5. Patient Health Questionnaire – 8 items (PHQ-8)
Patient Health Questionnaire – 8 items is a patient-reported outcomes questionnaire which 
consists of 8 items to screen for the subject depression level. 
The PHQ-8 should be completed at the Screening Visit.  At Screening Visit, if PHQ-8 total 
score ≥15, the subject will not be included in the study. 
7.6.6. Patient Global Impression of Change- Vitiligo (PGIC-V)
The PGIC-V is a 1-item questionnaire is designed to assess a subject’s impression of disease 
improvement relative to before the intervention on a 7 point Likert scale ranging from “Very 
much improved” to “Very much worse” with “no change” in the middle.  The PGIC-V 
should be completed as per Schedule of Activities.
7.6.7. EQ-5D-5L 
The EQ-5D-5L and VAS is a validated, standardized, generic instrument that is the most 
widely used preference-based health-related quality of life questionnaire in cost-effectiveness 
and health technologies assessment (HTA).5,11,15,32  The measure is a well-established 
instrument used to measure health states and utilities in various diseases areas.  The measure 
contains five items that cover mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression as well as a VAS to assess overall health status.  The EQ-5D-5L should 
be completed as per Schedule of Activities.
7.6.8. Healthcare Resource Utilization (HCRU) 
In order to get an assessment of the subject’s Healthcare Resource Utilization (HCRU), 
subjects will be asked about the number of visits and use of the healthcare system outside of 
that provided within the clinical trial.  Questions will be asked to gauge any hospitalizations, 
surgical procedures, or medical visits stratified by those which are vitiligo related or not.
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7.12. Rater Qualifications 
Clinical evaluations of vitiligo will be performed by an experienced and qualified 
dermatologist (board certified or equivalent).  An experienced and qualified 
non-dermatologist physician or experienced medical professional with experience in the 
conduct of vitiligo clinical trials may be permitted to perform the clinical evaluations of 
vitiligo when designated by primary site investigator.  The evaluator must receive and 
document protocol specific and applicable efficacy assessment scales training prior to 
performing these evaluations.  To assure consistency and reduce variability, the same 
evaluator must assess all dermatological clinical evaluations for any individual subject 
throughout the study whenever possible; a back-up experienced and qualified, 
protocol-trained evaluator will only be allowed and documented in case of emergency or 
special situations when the designated evaluator is unable to perform the evaluation.
7.13. Sun Exposure Check
The sun exposure information will be captured daily via electronic-diary (E-diary) as per 
Schedule of Activities. Compliance of E-diary will be monitored.  Delegated site staff will 
review compliance with subjects at each visit and counsel as appropriate.  If a subject has 
repeated non-compliance, the subject should be re-trained.  If a subject is unable to complete 
the E-diary due to documented technical disability or other limitation, the subject will be 
permitted to enter or remain in the study.  No deviations will be recorded in regards to
E-diary compliance. 
7.14. Fitzpatrick Skin Type Assessment
The skin type assessment will be done at the Screening visit using the Fitzpatrick Skin 
Phototype assessment (Appendix 9).  This is used to classify a person’s skin type by their 
response to sun exposure (ie, burning or tanning).
7.15. Requests for Results of Tests and Procedures Not Part of the Study (if applicable)
If during the event adjudication (Section 9.9), the specific documents are needed to support 
event adjudication by the Adjudication/Review Committees, additional tests or procedures 
that are not part of the study but that could be related to the study may be requested. Copies 
of the reports of these tests may be requested.  
Event documentation will vary with the event requiring adjudication and may include (but 
not be limited to): hospital discharge summaries, operative reports, clinic notes, diagnostic 
tests, pathology reports, autopsy reports and death certificate information, as applicable.
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8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening,
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 


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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/Early Termination section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 28 calendar days after the last administration of the investigational product.
For subjects who are screen failures, the active collection period ends when screen failure 
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8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor. If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
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. Adverse Reactions and Serious Adverse Reactions
An adverse reaction (AR) is any untoward and unintended responses to an investigational 
medicinal product (IMP) related to any dose administered.  This implies a reasonable 
possibility of a causal relationship between the event and the IMP. 


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A serious adverse reaction (SAR) is an adverse reaction which meets the criterion of 
‘seriousness’ as described in Section 8.2.3.  
Suspected unexpected serious adverse reactions (SUSARs) are serious adverse reactions 
(SARs) that are unexpected per the reference safety information (RSI) in the respective IBs 
for PF-06651600 and PF-06700841. 
8.2.5. 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.
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;


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
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.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE.  For purposes of 
consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.1.1. 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).  


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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:

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), 


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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.
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. Potential Cases of Decreased eGFR 
In the PF-06700841 FIH study B7931001, serum creatinine elevation was reported across 
dose levels in both healthy volunteer and psoriasis patients.  The proposed mechanism for the 
observed serum creatinine increases in study B7931001 is inhibition of creatinine transport in 
the kidney (ie, transporter-mediated rather than direct nephrotoxicity).
All subjects who are assigned to receive PF-06700841 in the Extension Period will have 
serum creatinine based and serum cystatin-C based eGFR calculated at EXD1 Visit upon 
entry into the study. 
Abnormal values in serum creatinine concurrent with absence of increase in blood urea 
nitrogen (BUN) that meet the below criteria, in the absence of other causes of kidney injury, 
are considered important medical events. 
Estimated GFR using serum creatinine (2009 CKD-EPI eGFR) {Levey, 2009 #25} and 
serum cystatin C (2012 CKD-EPI eGFR)14 will be determined at times specified in the 
Schedule of Activities.  If an individual subject who is assigned to receive PF-06700841 in 
the Extension Period demonstrates a CONCOMITANT serum creatinine based AND 
serum cystatin C based eGFR decline of ≥30% compared to the subject’s baseline 
eGFR, then the subject should not be further dosed and adequate, immediate, supportive 
measures and immediate evaluation by nephrologist (preferably within 24 hours) with 
appropriate management should be taken for evaluation and treatment as clinically indicated.  
If the subject cannot be seen by a nephrologist within 24 hours, then the subject should be 
sent to a local emergency room for assessment of renal function.  Results should be repeated 
as indicated by the nephrologist or weekly at a minimum until the eGFR returns to baseline 
±15% or the renal parameters are deemed to be stable by the nephrologist and/or PI.  eGFR 
results will be communicated to the treating physician. 


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Subjects should return to the investigational site and be evaluated as soon as possible, 
preferably within 24 to 48 hours from awareness of the abnormal eGFR (CONCOMITANT 
serum creatinine based AND serum cystatin C based eGFR decline of ≥30% compared to the 
subject’s baseline eGFR) result for a safety follow-up visit.  This evaluation should include 
laboratory tests, detailed history, and physical assessment.  In addition to repeating serum 
creatinine and serum cystatin C, laboratory tests should also include: serum BUN, serum CK, 
serum electrolytes (including at a minimum potassium, sodium, phosphate/phosphorus, 
calcium), in addition to urine dipstick, urine microscopic examination, and urinary indices.  
All cases confirmed on repeat testing as meeting the above pre-set laboratory criteria, with no 
other cause(s) of laboratory abnormalities identified should be considered as important 
medical event irrespective of availability of all the results of the investigations performed to 
determine etiology of the abnormal serum creatinine. 
All relevant test results will be forwarded to Pfizer for review within 30 days of receipt by 
the PI. 
This requirement applies to all subjects assigned to receive PF-06700841 in the Extension 
Period.
8.4.3. 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.
8.4.3.1. 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 


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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 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
A special safety concern (SSC), fetal cleft lip, was reported in the B7931004 (investigating 
PF-06700841 to treat psoriasis) trial affecting a singleton pregnancy of a subject on multiple 
concomitant medications including an herbal supplement which carried a pregnancy warning. 


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8.4.3.2. 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.
8.4.3.3. 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.
8.4.4. 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
8.4.4.1. 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.
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9.7. Interim Analysis during the Dose Ranging Period
The statistical analysis plan and the interim analysis plan for this protocol may include an
interim analysis using percent change from baseline in VASI score for all active treatments.  
Details regarding the analysis procedures to be used for the interim analysis will be provided
in the interim analysis plan (IAP).  The interim analysis may be performed when
approximately 50% of subjects have completed or had the chance to complete the Week 24
visit.  The objective of this interim analysis is to determine if there is evidence of lack of
differentiation (“futility”) for the active treatments compared to placebo.  The interim 
analysis will be based on a total of approximately 165 subjects who complete or had the 
chance to complete Week 24.
9.8. Data Monitoring Committee 
This study will use an internal review committee (IRC). 
The IRC will be responsible for ongoing monitoring of the safety of subjects in the study 
according to the charter.  The IRC will review accumulating renal safety data and may 
propose changes to the protocol as needed to ensure subject safety.  The IRC may also 
review results of any interim analyses as described in Section 9.6.  The recommendations 
made by the IRC to alter the conduct of the study will be forwarded to Pfizer management 
for final decision.  Pfizer will forward such decisions, which may include summaries of 
aggregate analyses of endpoint events and of safety data that are not endpoints, to regulatory 
authorities, as appropriate. 
9.9. Safety Adjudication Committees
The identification of events requiring submission to an adjudication/review committee may 
be made by the study site and communicated to Pfizer or designee. Events requiring review, 
including opportunistic infections, cardiovascular, and malignancy events may also be 
identified by the Pfizer Study Team or designee during the review of subject data listings or 
by site monitors during routine monitoring of subject’s study records. The Pfizer Study 
Team or designee will notify the study site of any events should they identify. 
The Pfizer Study Team or designee will provide a listing of specific documents needed to 
support event adjudication by the Adjudication/Review Committees. Obtaining and 
submitting the documentation will be the responsibility of the study site. Event 
documentation will vary with the event requiring adjudication and may include (but not be 
limited to): hospital discharge summaries, operative reports, clinic notes, diagnostic tests, 
pathology reports, autopsy reports and death certificate information, as applicable.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.


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During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. 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 shall ensure that the 
CRFs are securely stored at the study site in encrypted electronic and/or paper form and will 
be password protected or secured in a locked room to prevent access by unauthorized third 
parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases the source documents are the hospital or the physician's chart.  In these cases, 
data collected on the CRFs must match those charts. 


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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.  The 
investigator must ensure that the records continue to be stored securely for so long as they are 
retained.
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.


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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 
Helsinki.
12.3. Subject Information and Consent
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of subject personal data.  Such 
measures will include omitting subject names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws. 
The personal data will be stored at the study site in encrypted electronic and/or paper form 
and will be password protected or secured in a locked room to ensure that only authorized 
study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, subject names will be removed and will be replaced by a single, specific, numerical 
code, based on a numbering system defined by Pfizer.  All other identifiable data transferred 
to Pfizer or other authorized parties will be identified by this single, subject-specific code. 
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 the Clinical Study Agreement and 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, the sharing of data relating to the study and possible risks associated 
with participation, including the risks associated with the processing of the subject’s personal 
data.  The investigator further must ensure that each study subject is fully informed about his 
or her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.


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The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed, unless a waiver of 
informed consent has been granted by an IRB/EC.  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 All Participating Countries
End of trial in all participating countries is defined as last subject last visit (LSLV). 
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06651600 and PF-06700841 at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 7 business 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 trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.


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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.


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


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16. REFERENCES
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vitiligo with the topical Janus kinase inhibitor ruxolitinib: a 32-week open label 
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Kim, S., H. Heaton, L. Y. Liu and B. A. King (2018). "Rapid repigmentation of vitiligo 
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Kruger, C. and K. U. Schallreuter (2012). "A review of the worldwide prevalence of 
vitiligo in children/adolescents and adults." Int J Dermatol 51(10): 1206-1212.
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Levey, A. S., L. A. Stevens, C. H. Schmid, Y. Zhang, A. F. Castro, H. I. Feldman, J. W. 
Kusek, P. Eggers, F. Van Lente, T. Greene and J. Coresh (2009). "A New Equation to 
Estimate Glomerular Filtration Rate." Annals of internal medicine 150(9): 604-612.
21.
Liu, L. Y., J. P. Strassner, M. A. Refat, J. E. Harris and B. A. King (2017). 
"Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require 
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Liu, L. Y., J. P. Strassner, M. A. Refat, J. E. Harris and B. A. King (2017). 
"Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require 
concomitant light exposure." Journal of the American Academy of Dermatology 77(4): 
675-682.e671.


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23.
Mohammad, T. F., M. Al-Jamal, I. H. Hamzavi, J. E. Harris, G. Leone, R. Cabrera, H. 
W. Lim, A. G. Pandya and S. M. Esmat (2017). "The Vitiligo Working Group 
recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo." 
J Am Acad Dermatol 76(5): 879-888.
24.
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P. Price (1995). "Serum cystatin C measured by automated immunoassay: A more 
sensitive marker of changes in GFR than serum creatinine." Kidney International 47(1): 
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25.
Osman, A., C. L. Bagge, P. M. Gutierrez, L. C. Konick, B. A. Kopper and F. X. Barrios 
(2001). "The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with 
clinical and nonclinical samples." Assessment 8(4): 443-454.
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Taieb (2015). "Vitiligo." Nature Reviews Disease Primers 1: 15011.
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Posner, K., M. A. Oquendo, M. Gould, B. Stanley and M. Davies (2007). "Columbia 
Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal 
Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants." The 
American journal of psychiatry 164(7): 1035-1043.
28.
Rothstein, B., D. Joshipura, A. Saraiya, R. Abdat, H. Ashkar, Y. Turkowski, V. Sheth, 
V. Huang, S. C. Au, C. Kachuk, N. Dumont, A. B. Gottlieb and D. Rosmarin (2017). 
"Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib." Journal of the 
American Academy of Dermatology 76(6): 1054-1060.e1051.
29.
Taïeb, A. and M. Picardo (2009). "Vitiligo." New England Journal of Medicine 360(2): 
160-169.
30.
van Geel, N., J. Lommerts, M. Bekkenk, A. Wolkerstorfer, C. A. Prinsen, V. 
Eleftheriadou, A. Taieb, M. Picardo, K. Ezzedine and R. Speeckaert (2016). 
"Development and Validation of the Vitiligo Extent Score (VES): an International 
Collaborative Initiative." J Invest Dermatol 136(5): 978-984.
31.
van Geel, N., J. E. Lommerts, M. W. Bekkenk, C. A. Prinsen, V. Eleftheriadou, A. 
Taieb, M. Picardo, K. Ezzedine, A. Wolkerstorfer, R. Speeckaert and G. international 
Vitiligo Score Working (2017). "Development and validation of a patient-reported 
outcome measure in vitiligo: The Self Assessment Vitiligo Extent Score (SA-VES)." J 
Am Acad Dermatol 76(3): 464-471.
32.
Wille, N., X. Badia, G. Bonsel, K. Burström, G. Cavrini, N. Devlin, A.-C. Egmar, W. 
Greiner, N. Gusi, M. Herdman, J. Jelsma, P. Kind, L. Scalone and U. Ravens-Sieberer 
(2010). "Development of the EQ-5D-Y: a child-friendly version of the EQ-5D." Quality 
of Life Research 19(6): 875-886.


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Yamaguchi, Y. and V. J. Hearing (2014). "Melanocytes and their diseases." Cold Spring 
Harb Perspect Med 4(5).
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Zhu, Y., X. Ye, B. Zhu, X. Pei, L. Wei, J. Wu and W. Zhao (2014). "Comparisons 
between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology 
Collaboration) Equations and Other Four Approved Equations." PLoS ONE 9(1): 
e84688.
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O'Sullivan LA, Liongue C, Lewis RS, et al. Cytokine receptor signaling through the 
Jak-Stat-Socs pathway in disease. Mol Immunol. 2007; 44(10):2497-506.
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Eleftheriadou V, Thomas K, Ravenscroft J, et al. Feasibility, double-blind, randomised, 
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Trials 2014; 15:51.
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phototherapy for the treatment of vitiligo: a randomized multicenter trial. JAMA 
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Sehrawat M, Arora TC, Chauhan A, et al. Correlation of Vitamin D Levels with 
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Hegazy RA, Fawzy MM, Gawdat HI, et al. T helper 17 and Tregs: a novel proposed 
mechanism for NB-UVB in vitiligo. Exp Dermatol 2014; 23(4):283-6.
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Bansal S, Sahoo B, Garg V. Psoralen-narrowband UVB phototherapy for the treatment 
of vitiligo in comparison to narrowband UVB alone. Photodermatol Photoimmunol 
Photomed 2013; 29(6):311-7.
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Abdel-Naser MB, El-Khateeb EA, Sallam TH, et al. Endothelin-1 is significantly 
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Hamzavi I, Jain H, McLean D, et al. Parametric modeling of narrowband UV-B 
phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring 
Index. Arch Dermatol 2004; 140(6):677-83.
47.
Rork JF, Rashighi M, Harris JE. Understanding autoimmunity of vitiligo and alopecia 
areata. Curr Opin Pediatr. 2016;28(4):463–469. 
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Harris JE. Vitiligo and alopecia areata: apples and oranges? Exp Dermatol 2013; 
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Batchelor et al. Validation of the Vitiligo Noticeability Scale: a patient reported 
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Appendix 1. Abbreviations
This following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
AA
alopecia areata
AE
adverse event
AIFA
Italian Medicines Agency 
ALT
alanine aminotransferase
AR
adverse reaction
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the concentration-time curve 
AUC24
area under the plasma concentration-time curve from time zero 
to 24 hours
AUCinf
area under the plasma concentration-time curve from time zero 
to infinity
AUClast
area under the plasma concentration time curve from time zero 
extrapolated to the last quantifiable concentration
AUCτ
area under the concentration-time curve from zero to 24 hours 
(QD) or zero to 12 hours (BID) post-dose at steady state
BA
bioavailability
BAEP
Brainstem Auditory Evoked Potential
BBS
biospecimen banking system 
BCG
bacille calmette guérin 
BID
twice a day
BMX
bone marrow-expressed kinase 
BTK
bruton’s tyrosine kinase 
BP
blood pressure
BSA
Body surface area
BUN
blood urea nitrogen
CDS
core data sheet
CI
confidence interval 
CK
creatine kinase
CL
clearance
CL/F
Apparent total clearance of the drug from plasma after oral 
administration
Cmax
Maximum (peak) plasma concentration
CMV
cytomegalovirus 
CO
cross-over
COEOT
cross-over end of treatment
COVID-19
Coronavirus Disease 2019
CRF
case report form
CSA
clinical study agreement
CsA
cyclosporine A 


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Abbreviation
Term
CSF
cerebrospinal fluid
CSR
clinical study report
C-SSRS
Columbia suicide severity rating scale
CT
computed tomography 
CTA
clinical trial application
CTCAE
common terminology criteria for adverse events
CYS
cysteine
DAI
dosage and administration instructions
DDI
drug-drug interaction
DLQI
dermatology life quality index 
DMARD
Disease-modifying antirheumatic drug
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EBV
epstein barr virus
EC
ethics committee
ECG
electrocardiogram
EDMC
external data monitoring committee 
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
EE
Ethinyl Estradiol
EFD
embryo-fetal development
Emax
maximum effect
eGFR
estimated glomerular filtration rate 
ELISA
enzyme-linked immunosorbent assay 
EOS
end of study
EOT
end of treatment
EPO
erythropoietin
EQ-5D-5L
EuroQol 5 dimension 5 level
ESR
erythrocyte sedimentation rate
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration (United States)
FDAAA
Food and Drug Administration Amendments Act (United States)
FIH
first-in-human
FSH
follicle-stimulating hormone
fu
fraction unbound 
FU
Follow-up
GCP
good clinical practice
GI
gastrointestinal 
GLMM
generalized linear mixed model
CCI


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Abbreviation
Term
GM-CSF
granulocyte-macrophage colony-stimulating factor
GST
glutathione-S-transferase 
HADS
hospital anxiety and depression scale 
HbA1c
glycosylated hemoglobin A1c
HBcAb
hepatitis B core antibody 
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen 
HCRU
healthcare resource utilization
HCVAb
hepatitis C antibody
HEENT
head, eyes, ears, nose and throat
HIV
human immunodeficiency virus
HRQL
health-related quality of life
hsCRP
high-sensitivity C-reactive protein
HSV
herpes simplex virus
HSV1
herpes simplex virus type 1
HSV2
herpes simplex virus type 2
IB
investigator’s brochure
IC50
the half maximal inhibitory concentration
ICH
International Conference on Harmonisation
ID
identification
IFN
interferon alfa
IFN
interferon gamma
IGA
investigator’s global assessment
IGRA
Interferon Gamma Release Assay
IL
interleukin 
IMP
investigational medicinal product 
IND
investigational new drug application
INR
international normalized ratio
IOBU-SDMC
Internal Oncology Business Unit-Safety Data Monitoring 
Committee
IP
investigational product
IRB
institutional review board
IRC
internal review committee
ITK
inducible T-cell kinase 
IRT
interactive response technology
IUD
intrauterine device
IVRS
interactive voice response system
IWR
interactive web response
JAK
janus kinase
LFT
liver function test
CCI
CCI
C
CI


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Abbreviation
Term
LLN
lower limit of normal 
LLQ
lower limit of quantitation 
LN
levonorgestrel
LOAEL
lowest observed adverse effect level 
LPD
local product document
LSLV
last subject last visit 
MAD
multiple ascending dose
MATEs
multidrug and toxin extrusion proteins
MDCK/MDR1
Madin Darby canine kidney cell line
MDR1
multidrug resistance 1 gene
mITT
modified intention-to-treat
MMRM
mixed-effect models repeated measures
MRI
magnetic resonance imaging
MTX
methotrexate
N/A
not applicable
NADPH
nicotinamide adenine dinucleotide phosphate 
nbUVB
narrow band ultraviolet B 
NK
natural killer cells
NRI
non-responder imputation
NRS
numerical rating scale
OAT2
organic anion transporter 2
OBU
oncology business unit
OC
oral contraceptive 
OCT2
organic cation transporter 2 
PCD
primary completion date
PI
principal investigator
PFS
pre-filled syringe
PGIC-V
patient global impression of change in vitiligo 
P-gp
P-glycoprotein 
PHQ-8
patient health questionnaire – 8 items
PK
pharmacokinetic
POC
proof-of-concept
POM
proof of mechanism 
PPD
purified protein derivative 
PRO
patient reported outcomes
PsO
psoriasis
PT
prothrombin time
PtGA
patient global assessment 
QD
once daily
QFT-G
QuantiFERON®-TB Gold 
CC
I
CCI
CCI


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Abbreviation
Term
QFT-GIT
QuantiFERON®-TB Gold In-Tube 
QTcF
the corrected QT interval by Fredericia
Rac
accumulation ratio 
RLK/TXK
resting lymphocyte kinase 
RRCK
ralph russ canine kidney cells
RSI
reference safety information
s-IGA
static investigator global assessment 
SA-VES
self assessment vitiligo extent score
SAD
single ascending dose
SAE
serious adverse event
SALT
severity of alopecia tool
SAP
statistical analysis plan
SAR
serious adverse reaction
SBQ-R
suicidal behaviors questionnaire –revised
SC
subcutaneous
SCL
supply chain lead
SD
standard deviation
SOA
Schedule of activities
SOC
system organ class
SOP
standard operating procedure
SPC
summary of product characteristics
SPF
sun protection factor
SRSD
single reference safety document
SSC
special safety concern 
STATs
signal transducers and activators of transcription
SUSARs
suspected unexpected serious adverse reactions 
t½
half life
TB
tuberculosis 
TDAR
T cell-dependent antibody response
TEC
tyrosine kinase expressed in hepatocellular carcinoma
TEAE
treatment-emergent adverse event
TH1
type 1 helper T cell 
TH2
type 2 helper T cell 
Tmax
the time after administration of a drug when the maximum 
plasma concentration is reached
TYK2
tyrosine kinase 2
UGT
UDP-glucuronosyltransferase 
ULN
upper limit of normal
US
United States
USPI
United States package insert
UVA
ultraviolet A light
CCI
CCI


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Abbreviation
Term
UVB
ultraviolet B light
UVR
ultraviolet radiation
VASI
vitiligo area scoring index
VES
vitiligo extent score
VitiQoL
vitiligo specific quality of life 
VNS
Vitiligo Noticeability Scale 
Vz/F
Apparent volume of distribution during terminal phase after 
non-intravenous administration
VZV
varicella zoster virus
WOCBP
woman of child bearing potential


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Appendix 2. Prohibited Concomitant Medications 
This is not an all-inclusive list.  Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that are either moderate to potent CYP3A 
inhibitors or inducers or substrates, strong P-glycoprotein (P-gp) inhibitors, substrate of 
MDR1, or substrate of OCT2/MATE.
Moderate to Potent 
CYP3A Inhibitors*
Moderate to 
Potent CYP3A 
Inducers**
Substrates of CYP3A Strong P-gp 
inhibitors*
Substrates 
of MDR1 
Substrates of 
OCT2/MATE
Sensitive 
substrate to 
ABCG2=BCRP
Amprenavir
Avasimibe#
Simvastatin or 
Simvastatin-
containing products
Quinidine### Digoxin### Dofetilide###
Rosuvastatin##
Amiodarone 
Bosentan
Aprepitant
Barbiturates
Atazanavir
Carbamazepine#
Boceprevir
Efavirenz 
Casopitant
Etravirine
Cimetidine
Mitotane#
Ciprofloxacin
Modafinil
Clarithromycin#
Nafcillin
Cobicistat#
Phenobarbital#
Conivaptan#
Phenytoin#
Darunavir
Rifabutin#
Diethyldithiocarbamate Rifampin#
Diltiazem
St. John’s Wort#
Dronedarone
Talviraline
Elvitegravir#
Erythromycin
Fluconazole
Fluvoxamine
Imatinib
Indinavir#
Itraconazole#
Ketoconazole#
Lopinavir#
Mibefradil#
Mifepristone (RU486)
Nefazodone#
Nelfinavir#
Norfloxacin
Posaconazole#
Ritonavir#
Saquinavir#
Schisandra 
sphenanthera
Telaprevir
Telithromycin#
Tipranavir#
Tofisopam
Troleandomycin#
Verapamil
Voriconazole#
* 
Applicable to PF-06651600 and PF-06700841: All prohibited drugs that are CYP3A inhibitors or strong 
P-gp inhibitors (PF-06700841 only) require at least a 7 day or 5 half-lives (whichever is longer) prior to 
the first dose of study drug.  Note: Amiodarone requires discontinuation at least 290 days (~5 half-lives, 


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half-life averages ~58 days) prior to the first dose of IP.
** Applicable to PF-06651600 and PF-06700841: All prohibited drugs that are CYP3A inducers require at 
least a 28 day or 5 half-lives (whichever is longer) prior to the first dose of IP.
# 
Noted as potent inhibitors or inducers. 
## Applicable to PF-06651600: For Germany only
### Applicable to PF-06700841 only.
It is recommended that subjects avoid consumption of grapefruit juice exceeding 8 ounces (~240 ml) total in a 
day while in the study.
In a situation where appropriate medical care of a subject requires the use of a prohibited CYP3A 
inhibitor or inducer:
Moderate to potent inhibitors and inducers of CYP3A are not permitted in the study EXCEPT in emergency 
situations requiring no more than one day of administration.  Note: Amiodarone and mitotane are not 
permitted for any duration due to their long half-lives.  Topical (including skin or mucous membranes) 
application of antimicrobial and antifungal medications is permitted.






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Appendix 4. Management of Dermatological Events
Dermatologic Event (CTCAE v 4.0)
Course of Management
Acne/Acneiform Rash/Maculopapular Rash
Grade 1/2
1.
Investigator’s discretion for withdrawing   
study medication.
2.
Execute reasonable monitoring.
3.
Consider treatment with topical agents such as 
clindamycin or corticosteroids.
Grade 3
1.
Discontinue study medication.
2.
Monitor to resolution (defined as a Return to 
Baseline status).
3.
Consider treatment with topical agents such as 
clindamycin or corticosteroids.
Pruritus
Grade 1 Mild or localized
1.
Investigator’s discretion for withdrawing 
study medication.
2.
Execute reasonable monitoring.
3.
Consider treatment with topical agents such as 
clindamycin or corticosteroids.
Grade 2 Intense or widespread
1.
Discontinuation of the study medication may 
not be required unless condition is sustained 
>4 days or at the investigator’s discretion.
2.
Execute reasonable monitoring.
3.
Consider treatment with topical agents such as 
clindamycin or corticosteroids.
Grade 3 Intense or widespread and interfering 
with activities of daily living
1.
Permanently discontinue study medication.
2.
Monitor to resolution (Return to Baseline).
3.
Consider treatment with topical agents such as 
clindamycin or corticosteroids.


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Appendix 5. Guidelines for Subject Safety Monitoring and Discontinuation
These guidelines for subject safety monitoring and discontinuation are to be applied to all 
subjects in study B7981019.  Additional individual subject monitoring is at the discretion of 
the investigator and dependent on any perceived safety concerns.  Unscheduled clinical labs 
may be obtained at any time during the study to assess such concerns, and a subject may be 
withdrawn at any time at the discretion of the investigator.
Appendix 5.1. Monitoring
All potential treatment-related reports of rash will be followed up until resolution or 
agreement with Pfizer. 
The following laboratory abnormalities require re-testing within 1 week (upon receving 
the laboratory results) until resolution or agreement with Pfizer:

Absolute neutrophil count <2000/mm3 (2.0 x109/L);

Hemoglobin <9.0 g/dL;

Platelet count below <100,000/mm3 (100 x109/L);

Lymphocytes <600/mm3; <0.6x109/L;

CK >3xULN (this also triggers urine myoglobin).
Appendix 5.2. Discontinuation
Treatment will be discontinued for:
Subjects in Group 2 in Extension Period:

Subjects have <10% improvement in percent change in VASI at Extension Week 12 
from baseline at Week 24.
Adverse Events:

Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization;

Clinically meaningful, treatment related decline in hearing from baseline (refer to 
local guideline or equivalent);

Other serious or severe AEs, at the discretion of the investigator or sponsor.


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Potential Cases of Potential Drug-Related Rash:

Serious or severe drug-related rash at the discretion of the investigator or sponsor 
(Section 7.3.6.1.2). 
Potential Cases of Decreased eGFR:
If an individual subject who is assigned to receive PF-06700841 in the Extension Period 
demonstrates a CONCOMITANT serum creatinine-based AND serum Cystatin C-based 
eGFR decline of ≥30% compared to the subject’s baseline eGFR, then the subject should not 
be further dosed and adequate, immediate, supportive measures and immediate evaluation 
by nephrologist (preferably within 24 hours) with appropriate management should be 
taken for evaluation and treatment as clinically indicated.  If the subject cannot be seen by a 
nephrologist within 24 hours, then the subject should be sent to a local emergency room for 
assessment of renal function.  Results should be repeated as indicated by the nephrologist or 
weekly at a minimum until the eGFR returns to baseline ±15% or the renal parameters are 
deemed to be stable by the nephrologist and/or PI (see protocol Section 8.4.2).
Psychological Assessment
At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any behavioral 
question of the C-SSRS, the subject will be discontinued from the Dose Ranging Period or 
Extension Period and referred to a mental health professional for appropriate evaluation and 
treatment.  If the subject cannot be seen by a mental health professional within 24 hours, then 
the subject should be sent to a local emergency room for psychiatric assessment.
Vital Signs:
The following vital sign abnormality will require discontinuation if it is confirmed.  
Confirmation through re-testing should occur within 1 week:

Diastolic: recurrent or persistent (≥24 hrs) or symptomatic increase from baseline, in 
same posture, by >20 mmHg.
ECG: 
The following ECG abnormality will require discontinuation if it is confirmed by repeat 
ECG:
QT prolongation defined as a QTc ≥500 msec or an absolute change in QTc ≥60 msec.




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Appendix 6. Vitiligo Extent Score (VES)
www.vitiligo-calculator .com


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Appendix 7. Columbia Suicide Severity Rating Scale (C-SSRS)27
C-SSRS for Screening and Baseline Visit 


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CSSRS for any post-baseline visits


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Appendix 8. Pruritus Numeric Rating Scale (NRS) for Potential Drug-related Rash
Select the number that best describes your itching due to potential drug-related rash over the 
past 24 hours (check one number only).
10
9
8
7
6
5
4
3
2
1
0
10
9
8
7
6
5
4
3
2
1
0
No 
itching
Worst 
possible 
itching


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Appendix 9. Fitzpatrick Skin Type








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Appendix 11. Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
Eligibility
Study B7981019 has been fully recruited and the eligibility criteria are not impacted by any 
public emergencies, including the COVID-19 pandemic.  
Telehealth Visits
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of Activities
or unscheduled visits. The participant site visits may be changed to telehealth visits (if 
permitted by law or local guidance) to reduce risk of potential participant exposure to 
COVID-19. 
Telehealth visits may be used to continue to assess participant safety and collect data points. 
Telehealth includes the exchange of healthcare information and services via 
telecommunication technologies (eg, audio, video, video-conferencing software) remotely, 
allowing the participant and the investigator to communicate on aspects of clinical care, 
including medical advice, reminders, education, and safety monitoring. The following 
assessments must be performed during a telehealth visit: 

Review and record study intervention(s), including compliance and missed doses.

Review and record any AEs and SAEs since the last contact.  Refer to Section 8.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Section 4.4.1 and Section 7.1 regarding pregnancy tests.

Evaluate VASI and facial-VASI (site assessment). Refer to Section 7.4.1, 7.4.2, and 
7.4.3. A self-captured photos by the subject may aide in assessment of facial-VASI.  

Complete PRO measures in the following order: VitiQoL, PGIC-V, and VNS. Refer 
to Section 7.6. 


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Study participants must be reminded to promptly notify site staff about any change in their 
health status.
Alternative Facilities for Safety Assessments
Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local regulations.  
The local laboratory may be a standalone institution or within a hospital. The following 
safety laboratory evaluations may be performed at a local laboratory: 

Clinical laboratory tests listed in Section 7.3.8.2, including hematology, blood 
chemistry, urinalysis and other protocol specified tests.

Special safety assessment of serum creatinine and cystatin C, for estimation of eGFR.
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and 
certifications/accreditations for filing at the site.  Laboratory test results are to be provided to 
the site staff as soon as possible.  The local laboratory reports should be filed in the 
participant’s source documents/medical records. Relevant data from the local laboratory 
report should be recorded on the CRF.
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 IU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. 
Imaging
If the participant is unable to visit the study site for imaging assessment(s), the self captured 
photo APP (called “Pfizer Vitiligo Study B7981019” powered by Tissue Analytics) used by 
the subject may aide in assessment of facial-VASI. 
Qualified study site personnel must order, receive, and review results. 
Electrocardiograms
If the participant is unable to visit the study site for single 12-lead ECGs, the participant may 
visit an alternative facility to have the ECGs performed. Qualified study site personnel must 
order, receive, and review results. 


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Study Treatments
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study treatment
must be considered.
In situations where participants are quarantined or self-isolating, arrangements to send 
investigational product via courier may be implemented where allowable by law or by local 
guidance and with the participant’s verbal consent.
Investigational product appropriate for the individual participant based on the study period 
and treatment group, may be shipped by courier to study participants if permitted by local 
regulations and in accordance with storage and transportation requirements for the 
investigational product.  Pfizer does not permit the shipment of investigational product by 
mail. The tracking record of shipments and the chain of custody of investigational product
must be kept in the participant’s source documents/medical records.
Similar to investigational product dispensed at the clinical site, PF-06651600 tablets and 
matching placebo for oral administration will be in blisters and PF-06700841 tablets for oral 
administration will be in bottles. Investigational products should be stored in their original 
containers and in accordance with the labels. 
Participants will take the medication orally once daily. Participants should swallow the
tablets whole with 1 cup (240 mL or 2.4 DL) of ambient temperature water, without any 
manipulation or chewing. Participants will be encouraged to take the investigational 
product after breakfast whenever possible even though it may be taken with or without 
food.
Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an adverse event 
(AE) or serious adverse events (SAE) and appropriate medical intervention provided. 
Temporary discontinuation of the study intervention may be medically appropriate until the 
participant has recovered from COVID-19.
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
Efficacy Assessments
The efficacy assessments will be conducted to the best ability with available telehealth 
modality and calculate VASI and facial-VASI. If possible, obtain photographs of the target 
lesion with the best possible compliance with the Photography Instructions.

SAP_001.pdf: 
Protocol B7981019 (PF-06651600; PF-06700841)
Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 1
Protocol B7981019
A PHASE 2B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND 
SAFETY PROFILE OF PF-06651600 WITH A PARTIALLY BLINDED EXTENSION 
PERIOD TO EVALUATE THE EFFICACY AND SAFETY OF PF-06651600 AND 
PF-06700841 IN SUBJECTS WITH ACTIVE NON-SEGMENTAL VITILIGO
Statistical Analysis Plan 
(SAP)
Version:
6
Date:
25-Feb-2021


Protocol B7981019 (PF-06651600; PF-06700841)
Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 2
TABLE OF CONTENTS 
LIST OF TABLES.....................................................................................................................5
LIST OF FIGURES ...................................................................................................................6
1. VERSION HISTORY............................................................................................................7
2. INTRODUCTION ...............................................................................................................11
2.1. Study Objectives and Endpoints During Dose Ranging Period..............................11
2.2. Study Objectives and Endpoints During Extension Period.....................................14
2.3. Study Design ...........................................................................................................16
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................20
3.1. Primary Endpoint(s) ................................................................................................20
3.2. Secondary Endpoint(s) ............................................................................................21
3.2.1. Key Secondary Endpoint............................................................................21
3.2.2. Other Secondary Endpoints(s)....................................................................21
3.3. Exploratory Endpoint(s)..........................................................................................22
3.5. Baseline Variables...................................................................................................24
3.6. Safety Endpoints .....................................................................................................24
3.6.1. Adverse Events...........................................................................................24
3.6.2. Laboratory Data..........................................................................................24
3.6.3. Vital Signs ..................................................................................................25
3.6.4. Electrocardiograms.....................................................................................25
4. ANALYSIS SETS ...............................................................................................................25
4.1. FAS..........................................................................................................................25
4.2. Safety Analysis Set..................................................................................................25
4.3. Other Analysis Sets .................................................................................................25
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................25
5.1. Hypotheses and Decision Rules ..............................................................................26
5.2. General Methods .....................................................................................................27
5.2.1. Analyses for Binary Data............................................................................27
5.2.2. Analyses for Continuous Data....................................................................27
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5.3. Methods to Manage Missing Data ..........................................................................28
5.3.1. Efficacy Data ..............................................................................................28
5.3.1.1. Continuous efficacy data...........................................................28
5.3.1.2. Binary Efficacy Data.................................................................28
5.3.3. Missing data due to COVID-19..................................................................28
6. ANALYSES AND SUMMARIES ......................................................................................29
6.1. Analyses and Summaries During Dose Ranging Period.........................................29
6.1.1. Primary Endpoint........................................................................................29
6.1.1.1. Primary Analysis - Percent Change From Baseline in 
Central Read Facial-VASI Score at Week 24 ...................................29
6.1.1.2. Sensitivity/Robustness Analyses for Primary Endpoint............30
6.1.1.3. Exploratory Analysis for the Primary Endpoint Involving 
Facial-VASI Definition .....................................................................31
6.1.1.4. Supportive Analysis for the Primary Endpoint .........................31
6.1.2. Secondary Endpoint(s)................................................................................32
6.1.2.1. Key Secondary Endpoint: Central Read Facial-VASI75 ..........32
6.1.2.2. Secondary Endpoint: VASI50...................................................33
6.1.2.3. Secondary Endpoints: Percent Change From Baseline in 
Central Read Facial-VASI (Except Week 24), Site Assessment 
Facial-VASI, VASI, SA-VES, and Absolute Change From 
Baseline in VASI...............................................................................33
6.1.2.4. Secondary Endpoints: VASI 75, VASI 90 and VASI 100........33
6.1.2.5. Secondary Endpoints: Central Read and Site Assessment 
Facial-VASI 50/75/90/100 (Except Central Read Facial-
VASI75) ............................................................................................33
6.1.2.6. Secondary Endpoint: Change From Baseline in VitiQoL.........33
6.1.2.7. Secondary Endpoint: Proportion of Subjects achieving a 
Static Investigator Global Assessment score of 0 or 1, and at 
least 2-point Improvement at Week 24 .............................................34
6.1.3. Tertiary Endpoint(s)....................................................................................34
6.1.3.1. Tertiary Endpoints: Percent Change From Baseline in 
VES....................................................................................................34
6.1.3.2. Tertiary Endpoints: VES 50/75/90/100.....................................34
6.1.3.3. Tertiary Endpoints: Absolute Change From Baseline in 
Central Read and Site Assessment Facial-VASI and VES ...............34
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6.1.3.4. Tertiary Endpoints: VASI/Central Read Facial-VASI vs 
PGIS-V at Week 24...........................................................................34
6.1.3.5. Tertiary Endpoint: Change from Baseline in DLQI..................35
6.1.3.6. Tertiary Endpoint: Change from Baseline EQ-5D-5L ..............35
6.1.3.7. Tertiary Endpoint: Change from Baseline HCRU ....................35
6.1.3.8. Tertiary Endpoint: PHQ-8.........................................................35
6.1.3.9. Tertiary Endpoint: Facial Target Lesion Improvement (by 
Planimetry) ≥50% From Baseline at Week 24..................................35
6.1.3.10. Tertiary Endpoint: Proportion of “Much Improved” and 
“Very Much Improved” on PGIC-V .................................................35
6.1.3.11. Tertiary Endpoint: Proportion of “A lot less noticeable” 
or “No longer noticeable” on VNS....................................................36
6.1.3.12. Tertiary Endpoint: Change of Extent of Depigmentation 
in Target Lesion(s) ............................................................................36
6.1.3.14. Tertiary Endpoint: C-SSRS.....................................................37
6.1.3.15. Tertiary Endpoint: Hospital Anxiety and Depression 
Scale ..................................................................................................37
6.1.3.16. Tertiary Endpoint: Target Lesion Assessments for Stable 
Vitiligo and for Segmental Vitiligo, if any........................................38
6.1.3.17. Tertiary Endpoint: Dermoscopy..............................................38
6.1.4. Baseline and Other Summaries and Analyses ............................................40
6.1.4.1. Baseline and Other Summaries .................................................40
6.1.4.2. Study Conduct and Subject Disposition....................................40
6.1.4.3. Concomitant Medications, Non-Drug Treatments, and 
Dosing Compliance ...........................................................................40
6.1.5. Safety Summaries and Analyses.................................................................41
6.1.5.1. Adverse Events..........................................................................41
6.1.5.2. Laboratory Data.........................................................................41
6.1.5.3. Vital Signs.................................................................................42
6.1.5.4. Electrocardiogram .....................................................................42
6.1.5.5. Physical Examination................................................................42
6.2. Analyses and Summaries During Extension Period................................................42
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LIST OF FIGURES
Figure 1.
Study Design Schema for Screening Period and Dose Ranging 
Period........................................................................................................17
Figure 2.
Study Design Schema for Extension Period and Follow up Period .........18
Figure 3
Hochberg Procedure .................................................................................26
Figure 4
Dose Ranging Period to Extension Period Mapping................................43


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PFIZER CONFIDENTIAL
Page 7
1. VERSION HISTORY
This Statistical Analysis Plan (SAP) for study B7981019 is based on the Protocol
Amendment 5 dated 26 June 2020. 
Table 1.
Rationale of Major Changes in SAP Amendments
SAP Version
Change
Rationale
1
Not Applicable
Not Applicable
2

In Section 6.2 “Analyses and 
Summaries During Extension 
Period”, removed special 
instruction for placebo subjects 
from German sites. 
To clarify that placebo subjects 
who achieve VASI 100 in 
Germany will be treated the 
same as other countries.
3

Add Vitiligo Noticeability Scale 
(VNS) in Section 2.1, 2.2, 3.3, 
6.1.3 and 6.2.2.
Vitiligo Noticeability Scale 
(VNS) was added in Protocol 
amendment 4 as a Patient 
Report Outcome Measure.

Add Change of extent of 
depigmentation in target lesion(s)
in Section 2.1, 3.3, and 6.1.3.
Change of extent of 
depigmentation in target 
lesion(s) was in protocol as an 
exploratory endpoint.
4

Add Missing data rule for missing 
due to COVID-19 in 
Section 5.3.3, 6.1.1.1.

Add sensitivity analyses for 
primary endpoint excluding 
TeleHealth data in 
Section 6.1.1.2.

In Section 6.1.3, add analyses for 
PGIS-V, PGIC-V, and VNS; 
Modify analyses for EQ-5D and 
HADS.

Provide more details for 
Section 6.1.4.1.

Update Appendix 1 of analysis 
models and Appendix 2 of visit 
windows.
Predefine analyses to address 
COVID-19 impacts.
Update analyses methods for 
some PRO endpoints.
Visit windows are updated for 
analysis visit mapping.


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Page 8
SAP Version
Change
Rationale
5

Updated endpoints in dose-
ranging and extension period to 
align with protocol amendment 5.

Section 3.1: Added formula for 
central read facial-VASI and 
shifted formula for site 
assessment facial-VASI to 
appendix.

Section 3.2. & 3.3: Added 
subsection for new key secondary 
endpoint, and moved other 
endpoints in secondary and 
tertiary endpoints as appropriate 
to align with new study 
endpoints.

Section 5.1: Updated Hochberg 
test to reflect the 3 statistical tests 
being completed (instead of 5).

Section 5.2.2: Added description 
of ANCOVA analysis for 
continuous data.

Section 5.3.1.1: Added text for 
the missing data approach for 
models using ANCOVA.

Section 6.1: The analysis for the 
primary endpoint is now an 
ANCOVA model instead of 
MMRM. The MMRM analysis 
for the primary endpoint was 
shifted to a sensitivity analysis, 
and additional sensitivity analyses 
were added and separated into 
their own section. Supportive 
analysis for the primary endpoint 
was also added in the form of a 
Bayesian Emax model. 
Clarifying language added 
throughout section and additional 
subheaders added to describe the 
role of each analysis (primary 
analysis, supportive, exploratory, 
or sensitivity).

Section 6.1.2: Secondary analyses 
updated for site assessment 
facial-VASI and VASI. Both 
Updated as appropriate to align 
with new study endpoints.
Clarified the differences in 
central read and site assessment 
facial-VASI and their 
accompanying analyses.
Three statistical tests (instead of 
5) will be used to save alpha for 
most critical comparisons.
ANCOVA analyses will now be 
used for local read and site 
assessment facial-VASI and 
VASI, so updated text 
throughout to reflect new 
analyses.
Clarified the role of each type of 
analysis completed in support of 
the primary endpoint analysis.
Clarified potential analyses to 
be done if central-read facial-
VASI is performed during the 
extension period.
Added ANCOVA analyses to 
parallel analyses completed in 
the dose ranging period.


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SAP Version
Change
Rationale
now use ANCOVA instead of 
MMRM. The key secondary 
endpoint analyses were also 
added.

Section 6.2: Added text to 
emphasize that these analyses are 
for site assessment facial-VASI 
and that if central facial-VASI is 
assessed during the extension 
period, mirror analyses will be 
performed.

Section 6.2.2.2: Updated analyses 
for change from baseline and 
percent change from baseline 
VASI and site assessment 
facial-VASI to ANCOVA to 
mirror analyses from the 
dose-ranging period.

Section 6.2.2: Eliminated some 
analyses; will be moved to ad-hoc 
analyses.

Section 9.1.1: Updated summary 
of analyses to reflect new 
analyses being performed.

Section 9.5: Updated VitiQoL 
scoring algorithm and provided 
additional details.
Provided clarity for VitiQoL 
computation.
6

Section 3.3: Clarified that all 
lesion data used in the target 
lesion analyses is centrally read.
Defined formula for percent 
change from baseline in target 
lesion depigmentation.

Section 4.3: Defined additional 
analysis sets for the extension 
period.

Section 5.2.1: Clarified that 
GLMM results will only be 
reported if the model converges.

Section 5.3.1.1: Updated missing 
data language for ANCOVA from 
“complete case” to “observed 
cases”.
Clarified analyses and removed 
unnecessary figures and 
analyses.
Defined depigmentation 
formula and central read lesion 
analyses.
Added extension group analyses 
for long term efficacy 
(Extension group 3 from 
baseline to Week 48) and
nbUVB addon therapy effect 
(Extension group 2 vs. 3). 




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SAP Version
Change
Rationale
Extension group 1. Added 
extension analysis set
terminology throughout 6.2.

Section 6.2.2: Added two 
categories of subgroup analyses 
to be completed during the 
extension period. Added 
Extension Group 1 analyses.

Section 6.2.2.1.1: Added separate 
extension group analysis section 
for PF-06700841.

Section 9.1.2: Updated analysis 
sets.

Section 9.6: Updated analysis
method for categorical PGIS-V 
improvement to Fisher’s exact 
test
2. INTRODUCTION
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study B7981019.  This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment.
2.1. Study Objectives and Endpoints During Dose Ranging Period
Table 2.
Study Objectives and Endpoints During Treatment Period
Primary Objective:
Primary Endpoint:

To evaluate the efficacy of 
PF-06651600 dose/dosing regimens at 
Week 24 in adult subjects with active 
non-segmental vitiligo.

Percent change from baseline in central 
read facial vitiligo area scoring index 
(facial-VASI) at Week 24.

To evaluate the safety and tolerability 
of PF-06651600 over time in adult 
subjects with active non-segmental 
vitiligo.

Incidence of treatment-emergent adverse 
events (AEs) and serious adverse events 
(SAEs) up to Week 24.

Incidence of specific clinical laboratory 
abnormalities including but not limited to 
anemia, neutropenia, thrombocytopenia, 
lymphopenia, changes in lipid profile, 
and liver function tests (LFTs) up to 
Week 24.


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Secondary Objectives:
Secondary Endpoints:
Key Secondary Objective:

To evaluate the efficacy of 
PF-06651600 compared to placebo as 
measured by facial-VASI at Week 24 
in adult subjects with active 
non-segmental vitiligo.
Key Secondary Endpoint:

Proportion of subjects achieving central 
read facial-VASI75 (defined as at least 
75% improvement in central read 
facial-VASI from baseline) at Week 24.
Other Secondary Objectives:

To evaluate the efficacy of 
PF-06651600 compared to placebo as 
measured by other clinical assessments 
over time in adult subjects with active 
non-segmental vitiligo.
Other Secondary Endpoints:

Proportion of subjects achieving VASI50 
(defined as at least 50% improvement in 
VASI from baseline) at Week 24.

Percent change from baseline in VASI, 
central read and site assessment 
facial-VASI, self assessment vitiligo 
extent score (SA-VES), and absolute 
change from baseline in VASI at 
designated time points (except for 
Week 24 for central read facial-VASI).

Proportion of subjects achieving 
VASI50/75/90/100 (defined as at least 
50%/75%/90% or 100% improvement in
VASI from baseline) and central read and 
site assessment of the
facial-VASI50/75/90/100 (defined as at 
least 50%/75%/90% or 
100% improvement in facial-VASI from 
baseline at designated time points (except 
for Week 24 in VASI50 and central read 
facial-VASI75).

Change from baseline in vitiligo specific 
quality of life (VitiQoL) at designated 
time points.

Proportion of subjects achieving a static 
investigator global assessment (sIGA) 
0 or 1 and 2-point or greater 
improvement at Week 24.














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Subjects who have active non-segmental vitiligo (as defined in Protocol inclusion criterion 
#5) present and have met all other inclusion/exclusion criteria at the Screening Visit and 
Baseline Visit will be included in the study.  Photographs will be taken to verify eligibility
(Protocol inclusion criterion #5c). Investigators, subjects, and the sponsor study team will be 
blinded to treatment group during the study.
Subjects will be screened within 28 days prior to the first dose of Investigational product (IP) 
to confirm that they meet the subject selection criteria for the study. Subjects will be 
randomized for the 24-week Dose Ranging Period to 1 of 5 active treatment groups, or 
placebo, in the ratio of 4:4:4:3:3:4. 

An induction dose of 200 mg QD of PF-06651600 for 4 weeks followed by 
maintenance dosing of 50 mg QD of PF-06651600 for 20 weeks (n=60);

An induction dose of 100 mg QD of PF-06651600 for 4 weeks followed by 
maintenance dosing of 50 mg QD of PF-06651600 for 20 weeks (n=60);

A dose of 50 mg QD of PF-06651600 for 24 weeks (n=60);

A dose of 30 mg QD of PF-06651600 for 24 weeks (n=45);

A dose of 10 mg QD of PF-06651600 for 24 weeks (n=45);

Matching placebo for 24 weeks (n=60).
A biopsy sub-study will be performed at selected sites. Details will be described in the lab 
manual.
All subjects who complete the initial 24-week Dose Ranging Period may enter the Extension 
Period and will be allocated into one of 6 groups by pre-specified criteria. 

Group 1: Induction dose of 60 mg QD of PF-06700841 for 4 weeks followed by a 
4-week drug holiday (no IP), then maintenance dosing of 30 mg QD of PF-06700841 
for 16 weeks.  This arm is open label.

Group 2: Induction dose of 200 mg QD of PF-06651600 plus standardized narrow 
band UVB (nbUVB) add-on therapy for 4 weeks followed by maintenance dosing of 
50 mg QD of PF-06651600 plus standardized nbUVB add-on therapy for 20 weeks.
Subjects must provide nbUVB consent.  Subjects who have <10% improvement in 
percent change in VASI at Extension Week 12 from the baseline value at Dose 
Ranging Period Week 24 will be discontinued from the treatment and enter Follow-up 
Period.  This arm is open label.

Group 3: Induction dose of 200 mg QD of PF-06651600 for 4 weeks followed by 
maintenance dosing of 50 mg QD of PF-06651600 for 20 weeks. This arm is double 
blinded.

Group 4: 50 mg QD of PF-06651600 for 24 weeks. This arm is double blinded.


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•
Group 5: 30 mg QD of PF-06651600 for 24 weeks. This arm is double blinded.
•
Group 6: No IP will be administered. Observation Period for 24 weeks. Visits will 
be conducted every 4 weeks until EOS or until 30% or greater depigmentation from 
baseline VASI occurs, whichever is shorter.  No Follow-up Period required.  This arm 
is open.
Subjects in Group 1 and 2 who provide consent for the biopsy sub-study will participate in 
the biopsy sub-study at selected sites during the Extension Period.  An optional biopsy will 
be performed at Follow-up Visit 1 only for subjects who provide biopsy consent.
Subjects who complete the Extension Period (except for Group 6) or withdraw early from 
treatment will enter the Follow-up Period. Subjects who discontinue during the initial Dose 
Ranging period will enter the 8-week Follow-up Period and will not be eligible for the 
Extension Period. 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
The primary endpoint for this study is percent change from baseline in central read 
facial-VASI score at Week 24.  Baseline is defined as the last measurement prior to 
randomization (Day 1). Percent change from baseline is defined as the value at a specific 
visit minus the baseline value, divided by baseline value and multiplied by 100%, ie,
% change from BL central read facial VASI ൌ
post BL central read facial VASI െBL central read VASI
BL central read VASI
ൈ100
A negative percent change from baseline in central read facial-VASI signifies an 
improvement.
The central read facial-VASI is calculated using a formula that includes contribution of 
affected facial surface areas showing all six (6) different depigmentation rates (0.1, 0.25, 0.5, 
0.75, 0.9 and 1) with a modified method described by Hamzavi, et al:3
Facial VASI (central read) = Ʃ [Affected Facial Surface Area] × 4 × [Depigmentation Rates]
             
Six (6) Different Depigmentation Rates
The calculation of % affected total body surface area (BSA) is shown below:
Affected facial surface area × 4 = % Affected total body surface area  
As an exploratory analysis for central read facial-VASI, the above formula will be modified 
to use 3 instead of 4 (Section 6.1.1.3). Face is defined as the area from the hairline on top of 
the forehead to the jawline at the bottom of the cheeks. Facial VASI (central read) will range 
from 0.000 to 4.000 by defining the affected Facial Surface Area (expressed as a value 
between 0.0 to 1.0) being 4% of total Body Surface Area.


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The extent of depigmentation is expressed by the following percentages: 0, 10%, 25%, 50%, 
75%, 90%, or 100%.  

100% depigmentation: no pigment is present;

90% depigmentation: specks of pigment are present;

75% depigmentation: the depigmented exceeds the pigmented area;

50% depigmentation: the depigmented and pigmented areas are equal;

25% depigmentation: the pigmented area exceeds the depigmented area; and 

10% depigmentation: only specks of depigmentation are present. 
Scalp, neck, eyebrows, eyelashes, and vermilion will be excluded from this calculation,
although the total VASI assessment includes all of these regions.
3.2. Secondary Endpoint(s)
3.2.1. Key Secondary Endpoint
The key secondary endpoint is the proportion of subjects achieving at least 75% 
improvement from baseline in central read facial-VASI (central read facial-VASI75:
central read facial-VASI75 = 1 if percent change from baseline ≥75; central read 
facial-VASI75 = 0 if percent change from baseline <75) at Week 24 of the Dose-Ranging 
Period.
3.2.2. Other Secondary Endpoints(s)
A secondary endpoint for this study is percent change from baseline in VASI score at 
Week 24.  Baseline is defined as the last measurement prior to Randomization (Day 1).  
Percent change from baseline is defined as the value at a specific visit minus the baseline 
value, then divided by baseline value and multiply by 100%, ie,
% CFB VASI = ((post Baseline VASI – Baseline VASI)/Baseline VASI) X 100
Negative percent change from baseline in VASI signifies an improvement.
The total body VASI will be calculated using a formula that includes contribution from 
6 different body regions (possible range, 0-100):
VASI =     Ʃ         [Hand Units] × [Residual Depigmentation]
              Six (6) Body Sites
One hand unit, which encompasses the palm plus the volar surface of all the digits, is 
approximately 1% of the total body surface area and is used as a guide to estimate the 
baseline percentage of vitiligo involvement of each body region. 


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The body will be divided into 6 separate and mutually exclusive regions: head/neck, hands, 
upper extremities (excluding hands), trunk, lower extremities (excluding the feet), and feet. 
The axillary regions are included with the upper extremities, while the buttocks and inguinal 
regions are included with the lower extremities.  Genital area is included in trunk.  Face and 
neck lesions will be measured in this study.  The extent of residual depigmentation 
percentages are the same as described in Section 3.1. 
Another secondary endpoint is the proportion of subjects achieving at least 50% 
improvement in VASI (VASI50: VASI50 = 1 if percent change from baseline ≥50, 
VASI50 = 0 if percent change from Baseline <50) at Week 24. In addition to calculating the 
proportion of subjects achieving VASI50 at Week 24, VASI50 will be calculated at all 
intermediate time points in the Dose-Ranging Period.
The proportion of subjects achieving VASI50/75/90/100 (defined as at least 50%/75%/90% 
or 100% improvement in VASI from baseline) and central read and site assessment of the 
facial-VASI50/75/90/100 (defined as at least 50%/75%/90% or 100% improvement in central 
read and site assessment facial VASI from baseline) at designated time points (except for
Week 24 in VASI50 and central read facial-VASI75) will be calculated in a similar manner 
to VASI50. Measurement of site assessment facial-VASI is described in Appendix 5
(Section 9.5). 
In addition to the percent change from baseline in central read facial-VASI at Week 24, as 
described in the primary analysis, percent change from baseline in VASI, central read and 
site assessment facial-VASI, SA-VES, and absolute change from baseline in VASI at 
designated time points (except for percent change from baseline in central read facial-VASI 
at Week 24) will be used as secondary endpoints.  
The clinical evaluator of vitiligo will perform an assessment of the overall improvement of 
vitiligo and assign a static investigator global assessment (sIGA) score of 0 - 4. The 
proportion of subjects achieving a static investigator global assessment (sIGA) 0 or 1, and
≥2-point improvement at Week 24 is a secondary endpoint.
The change from baseline in vitiligo specific quality of life (VitiQoL) at designated time 
points is another secondary endpoint. 
3.3. Exploratory Endpoint(s)
Exploratory endpoints are the absolute change from baseline in central read and site 
assessment facial-VASI and VES, percent change from baseline in vitiligo extent score 
(VES), and proportion of subjects achieving VES50/75/90/100 (defined as at least 
50%/75%/90%/100% improvement in VES from baseline) at designated time points as 
specified in the SoA. 
Other exploratory endpoints include the change from baseline in dermatology life quality 
index (DLQI), EQ-5D-5L, and HCRU at designated time points as specified in SoA. They 
will be analyzed with all patients in the full analysis set (FAS). Baseline for all exploratory 
endpoints will be the last measurement prior to randomization. 








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After the initial Dose Ranging Period (Week 0-24) or the primary objective is completed for 
all the subjects, some members of the study team who are otherwise not responsible for study 
conduct until the database is locked will be unblinded so that a report for the corresponding 
data may be generated. The subjects, investigators, site personnel, and remaining study team 
members will remain blinded to randomized study treatments throughout the remainder
(including the Extension Period) of the study. The database will be officially released after
last subject last visit occurs. The final analysis will be then conducted and the CSR will be
issued. The decision rules for the final analyses are also described in the next section.
Per Section 9.1 of the Protocol, all sample size calculations are based on a conservative 
estimate of 260 participants completing the study. This conservative approach protects the
study’s power against missing data in the primary endpoint analysis (see Section 5.3.1.1). 
5.1. Hypotheses and Decision Rules
The hypotheses to be tested are that at least one of the following active treatment groups 
(200 mg QD/50 mg QD, 100 mg QD/50 mg QD, 50 mg QD/50 mg QD) is superior to 
placebo as measured by the percent change from baseline in central read facial-VASI at 
Week 24.  
Multiple comparisons among these 3 dose groups vs placebo will be conducted, applying 
Hochberg’s step-up procedure using observed p-values. The familywise Type 1 error rate 
will be controlled at one-sided 0.05.  The 30 mg and 10 mg groups are part of the 
dose-response assessment for the facial-VASI. 
The Hochberg procedure will be applied as described below.  
Figure 3
Hochberg Procedure
Adjustments for multiple comparisons will only be made for the primary endpoint at the 
Week 24 time point.  Statistical tests for 30 mg QD vs placebo and 10 mg QD vs placebo at 
Week 24 will also occur but these p-values will be considered descriptive. The 30 mg QD 
and 10 mg QD arms will help characterize the dose response curve.






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A summary of protocol deviations related to COVID-19 during the dose-ranging period and 
the extension period will be included as a listing.
6. ANALYSES AND SUMMARIES
6.1. Analyses and Summaries During Dose Ranging Period
Data will be cleaned, a snapshot of the database will be created, and efficacy and safety data 
from the 24-week Treatment Period will be summarized once the last subject last visit occurs 
for the initial 24-week Treatment Period. The following section provides details during the 
Dose Ranging Period. 
6.1.1. Primary Endpoint
6.1.1.1. Primary Analysis - Percent Change From Baseline in Central Read Facial-VASI 
Score at Week 24  
Endpoint: Percent change from baseline in central read facial-VASI 

Analysis time points: Week 24.

Analysis population: FAS.

Analysis methodology: Percent change from baseline will be analyzed using an
ANCOVA model (specified in Section 5.2.2). This model will include treatment, 
baseline efficacy score, and the Fitzpatrick skin type as covariates. 
Reporting results:

Descriptive data: n, mean, SD, median, min, and max at baseline and post-baseline 
visits will be presented for each treatment arm.

Percentage change from baseline: n, mean, SD, median, min, and max will be 
presented for each treatment arm. The LS means, 90% 2-sided CI for the LS means, 
difference between the LS means for each pair of PF-06651600 and placebo group 
and the corresponding 90% 2-sided CI will be presented.  

Listing by individual patient data for each of the 6 depigmentation rates used for the 
calculation of the central read facial-VASI for each treatment arm.
Figures:

LS mean percent change from baseline by visit and by treatment.

LS means and 90% 2-sided CI at Week 24.

Spaghetti panel plots of individual subject’s facial-VASI score by study day in dose 
ranging period.


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6.1.1.2. Sensitivity/Robustness Analyses for Primary Endpoint
To support the interpretation of the primary analysis, the following analyses will be 
performed:  
6.1.1.2.1. Sensitivity Analyses for Primary Endpoint using ANCOVA
One sensitivity analysis involving the ANCOVA model of Section 6.1.1.1 will be 
implemented. 

Percent change from baseline in central read facial-VASI using the following 
additional covariates in the ANCOVA model: total BSA (≤10% pigmentation vs. 
>10% pigmentation), geographic latitude (high vs. low, as data permits).
Analysis time points: Week 24 
Analysis population: FAS
Reporting results:

Percent change from baseline: n, LS means, 2-sided 90% CI for the LS means, 
difference between the LS means for each pair of treatment groups and the 
corresponding 2-sided 90% CI will be presented.  
Figures:

LS mean percent change from baseline by treatment at Week 24.

LS means and 90% 2-sided CI at Week 24.
6.1.1.2.2. Sensitivity Analyses for Primary Endpoint using MMRM
Endpoint: Percent change from baseline in central read facial-VASI 

Analysis time points: Week 24 (primary).

Analysis population: FAS.

Analysis methodology: Percent change from baseline will be analyzed using a linear 
mixed-effect repeated measures model (as specified in Section 5.2.2) with fixed 
effects for treatment, time (visit), treatment by time, baseline efficacy score, baseline 
efficacy score by time, and a random effect for subject. This model will also include
Fitzpatrick skin type as a baseline covariate.
Reporting results:

Descriptive data: n, mean, SD, median, min, and max at baseline and post-baseline 
visits will be presented for each treatment arm.


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
Percentage change from baseline: n, mean, SD, median, min, and max will be 
presented for each treatment arm. The LS means, 90% 2-sided CI for the LS means, 
difference between the LS means for each pair of PF-06651600 and placebo group 
and the corresponding 90% 2-sided CI will be presented.  
Figures:

LS mean percent change from baseline by visit and by treatment.

LS means and 90% 2-sided CI at Week 24 and all other intermediate time points.

A forest plot will be produced to present the primary endpoint at Week 24 and all the 
supporting and exploratory analyses (except the dose response analysis).
6.1.1.3. Exploratory Analysis for the Primary Endpoint Involving Facial-VASI 
Definition
An exploratory analysis that uses a facial surface area of 3% instead of 4% in the 
facial-VASI computation will also be performed. The formula for the central read 
facial-VASI, defined in Section 3.1, will use a multiplier of 3 instead of 4. The analysis 
method and reporting for these rescaled central read facial-VASI values will be the same as
Section 6.1.1.1. 
6.1.1.4. Supportive Analysis for the Primary Endpoint
To characterize the dose response for central read facial-VASI, a Bayesian 4-parameter 
maximum effect attributable to the drug (Emax) dose-response model will be used. The 
response function will be the percent change from baseline in central facial-VASI. To 
account for missing data, the MMRM output for the percent change from baseline in 
facial-VASI (estimates for each dose group and their standard errors) will be used for the 
response in the model.  There will be two dose response models: (1) using the average dose 
across the 24 week treatment period and (2) using an indicator function for the loading dose. 
For (1) the average doses in the model will be 75 mg (for 200/50 mg PF-06651600), 58 mg 
(for 100/50 mg PF-06651600), 50 mg, 30 mg, 10 mg and 0 mg. For (2) the doses in the 
model will be 50 mg, 30 mg, 10 mg, 0 mg with an indicator variable of 1 for 200/50 mg and
100/50 mg arms.
In modeling the dose response, diffusive prior distributions will be specified for placebo or 
e0, emax and dose yielding half of emax (ed50). Using these prior distributions for the true dose 
response function, we intend to present a Bayesian fit to the data. The fitted curve will be 
graphically displayed with 95% credible band.  Model-based estimation of treatment effect 
for each dose compared to placebo will be presented with 95% credible interval. The dose 
response analysis will be done using the R package clinDR.


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6.1.2. Secondary Endpoint(s)
6.1.2.1. Key Secondary Endpoint: Central Read Facial-VASI75
Endpoint: Central read facial-VASI75

Analysis time points: Week 24.

Analysis population: FAS.

Analysis methodology: binary data of subjects achieving at least 75% improvement 
in central read facial-VASI from baseline will be analyzed using Chan and Zhang’s 
exact CI method after applying the non-responder imputation discussed in
Section 5.3.1.2.
Reporting results:

Descriptive data: The number and percentage of subjects meeting central read facial-
VASI75 will be presented by visit (using observed data and non-responder 
imputation).

The RD from placebo and the 90% 2-sided CI will be presented.  
Figures:

Plot of the proportion of subjects meeting central read facial-VASI75 with 2-sided 
90% CI over time by treatment.

Forest plot will be produced for all the facial-VASI binary endpoints using the Chang 
and Zhang method.
6.1.2.1.1. Sensitivity Analysis for Key Secondary Endpoint
Endpoint: Central read facial-VASI75

Analysis time points: Week 24.

Analysis population: FAS.

Analysis methodology: Longitudinal central read facial-VASI75 may be analyzed by 
GLMM, with fixed factors of treatment, visit, treatment by visit, baseline central read 
facial-VASI score, baseline central read facial-VASI score by time (if possible), and a 
random subject effect. This model will also include Fitzpatrick skin type as a 
baseline covariate. This model will only be reported if the GLMM converges.
Reporting results:

P-values and inference for risk differences between active and placebo will be 
provided based on the link function of logit.


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Figures:

Plot of the proportion of subjects meeting central read facial-VASI75 with 2-sided 
90% CI over time by treatment.
6.1.2.2. Secondary Endpoint: VASI50
Endpoint: VASI50.

The analysis method, analysis population, and reporting results for VASI50 will 
match the analysis used for the key secondary endpoint and include reporting of the 
exact CI (Section 6.1.2.1) and GLMM if the model converges (Section 6.1.2.1.1).
6.1.2.3. Secondary Endpoints: Percent Change From Baseline in Central Read 
Facial-VASI (Except Week 24), Site Assessment Facial-VASI, VASI, SA-VES, and 
Absolute Change From Baseline in VASI
The analysis method, analysis population, and reporting results for percent change from 
baseline in central read facial-VASI (except Week 24) and SA-VES will be the same as the 
analysis used for MMRM sensitivity analysis for the primary endpoint (see
Section 6.1.1.2.2). 
The analysis method, analysis population, and reporting results for percent change from 
baseline in site assessment facial-VASI and VASI will be the same as the ANCOVA analysis 
for the primary endpoint (see Section 6.1.1.1). 
The analysis method for the absolute change from baseline in VASI will be the same as the 
ANCOVA analysis for the primary endpoint (see Section 6.1.1.1).
6.1.2.4. Secondary Endpoints: VASI 75, VASI 90 and VASI 100
The analysis method, analysis population, and reporting results for these endpoints will be 
identical to the analysis used for central read facial-VASI75 (Section 6.1.2.1).
6.1.2.5. Secondary Endpoints: Central Read and Site Assessment Facial-VASI 
50/75/90/100 (Except Central Read Facial-VASI75) 
The analysis method, analysis population, and reporting results for these endpoints will be 
identical to the analysis used for central read facial-VASI75 (Section 6.1.2.1).
6.1.2.6. Secondary Endpoint: Change From Baseline in VitiQoL
The change from baseline in total VitiQoL score and VitiQoL domain scores will be 
analyzed using the MMRM analysis as specified in Section 6.1.1.2.2. Details of the scoring 
algorithm are provided in Appendix 6.


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6.1.2.7. Secondary Endpoint: Proportion of Subjects achieving a Static Investigator 
Global Assessment score of 0 or 1, and at least 2-point Improvement at Week 24
Endpoint: sIGA.

Analysis time points: Scheduled time points in the SoA.

Analysis population: FAS.

Analysis methodology: the number and percentage of subjects in each category will 
be presented (see Section 5.2.1). Additionally, the number and percentage in each 
category will be analyzed using Chan and Zhang’s exact CI method after applying the 
non-responder imputation discussed in Section 5.3.1.2. 
Reporting results:

The number and percentage of the proportion of subjects achieving sIGA 0/1 and 
sIGA ≥2-point improvement will be presented by visit and treatment. The RD from 
placebo and the 90% 2-sided CI will also be presented.
6.1.3. Tertiary Endpoint(s)
6.1.3.1. Tertiary Endpoints: Percent Change From Baseline in VES
The analysis method will be the same as the analysis used for MMRM sensitivity analysis for 
the primary endpoint (see Section 6.1.1.2.2). Analysis time points will be Week 24 and all 
intermediate time points.
6.1.3.2. Tertiary Endpoints: VES 50/75/90/100 
The analyses for each endpoint will be identical to the analysis used for central read 
facial-VASI75 (Section 6.1.2.1).
6.1.3.3. Tertiary Endpoints: Absolute Change From Baseline in Central Read and Site 
Assessment Facial-VASI and VES
For absolute change from baseline in VES, the analysis method will be the same as the 
analysis used for MMRM sensitivity analysis for the primary endpoint (see
Section 6.1.1.2.2). Analysis time points will be Week 24 and all intermediate time points.
For absolute change from baseline in central read and site assessment facial-VASI, the
analysis method will be the same as the analysis used for primary analysis (see
Section 6.1.1.1). The analysis time point will be Week 24.
6.1.3.4. Tertiary Endpoints: VASI/Central Read Facial-VASI vs PGIS-V at Week 24
Endpoint: VASI/central read facial-VASI vs PGIS-V at Week 24; Change from baseline 
VASI/central read facial-VASI vs PGIS-V improvement categories (worsening (>0); no 
change, 1-point improvement, ≥2-point improvement) at Week 24.

Analysis time point: Week 24.


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
Analysis population: FAS.

Analysis methodology: Descriptive summary.
Reporting results:

A summary table of descriptive statistics will be provided. 
Figures:

Box and whisker plots of VASI/central read facial-VASI vs PGIS-V will be 
presented.
6.1.3.5. Tertiary Endpoint: Change from Baseline in DLQI 
The DLQI is calculated by summing the score of all questions. The maximum score is 
30 and the minimum is 0. The analysis method will be the same as the analysis used for 
MMRM sensitivity analysis for the primary endpoint (see Section 6.1.1.2.2). 
6.1.3.6. Tertiary Endpoint: Change from Baseline EQ-5D-5L 
The number and percentage of subjects in 5 levels of 5 dimensions will be summarized by 
visit and by treatment. Summary statistics (n, mean, SD, median, min, and max) for mean 
EQ-5D-5L utility score and EQ-5D-VAS score will be provided by visit and treatment. 
The EQ-5D-5L scoring manual will be provided separately. US-based weights will be used 
across all study sites.
6.1.3.7. Tertiary Endpoint: Change from Baseline HCRU 
The number and percent of subjects with at least one HCRU questionnaire event will be 
summarized by visit and treatment. Descriptive statistics of change from baseline of HCRU 
by each question will be provided by visit and treatment.
6.1.3.8. Tertiary Endpoint: PHQ-8
PHQ-8 is collected only at screening. Descriptive statistics of PHQ-8 score categories will 
be summarized by treatment group.
6.1.3.9. Tertiary Endpoint: Facial Target Lesion Improvement (by Planimetry) 
≥50% From Baseline at Week 24
If data permit, the proportion of subjects achieving ≥50% improvement from baseline at 
Week 24 will be summarized using descriptive statistics.
6.1.3.10. Tertiary Endpoint: Proportion of “Much Improved” and “Very Much 
Improved” on PGIC-V
Endpoint: PGIC-V; Change from baseline VASI / central read facial-VASI vs PGIC-V at 
Week 24.

Analysis time point: Week 24.


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
Analysis population: FAS.

Analysis methodology: PGIC-V will be summarized with frequency counts by each 
category at Week 24. The proportion of subjects in ‘Much Improved’ and ‘Very 
Much Improved’ will be compared to placebo using RD and CIs using the Chan and 
Zhang exact method.
Reporting results:

A table of RD for subjects achieving ‘Much Improved’ and ‘Very Much Improved’ in 
active treatment arms vs placebo will be provided.

A summary table of descriptive statistics will be provided. 
Figures:

Box and whisker plots of change from baseline VASI/central read facial-VASI vs 
PGIC-V will be presented.
6.1.3.11. Tertiary Endpoint: Proportion of “A lot less noticeable” or “No longer 
noticeable” on VNS 
The proportion of subjects in each category of VNS will be summarized by treatment groups.
Subjects who achieve VNS = 4 or 5 will be considered as a treatment success, ie, responders. 
The number and proportion of subjects achieving VNS = 4 or 5 at Week 24 will be provided 
by treatment group. 
If data permits, Chan and Zhang’s exact CI will be computed for the RD to compare the 
proportion of treatment success between PF-06651600 vs placebo at Week 24.
Box and whisker plots of change from baseline VASI/central read facial-VASI vs VNS at 
Week 24 will be presented.
6.1.3.12. Tertiary Endpoint: Change of Extent of Depigmentation in Target Lesion(s)
Endpoint: Percent change from baseline in depigmentation rate of target lesions.

Analysis time points: Week 24. 

Analysis population: FAS.

Analysis methodology: Percent change from baseline will be analyzed using an 
ANCOVA model (specified in Section 5.2.2). This model will include treatment, 
baseline score, location (if data available) and the Fitzpatrick skin type as covariates.


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Reporting results:
•
Desciptive data: n, mean, SD, median, min, and max at baseline and post-baseline 
visits will be presented for each treatment arm. The LS means and 90% 2-sided CI for 
the LS means will be presented.  
•
If data permits, Chan and Zhang’s exact CI method may be used to compare the 
proportion of depigmentation level improvement of 25% or more between 
PF-06651600 and placebo.
Figures:
•
LS mean percent change from baseline by visit and by treatment. 
6.1.3.14. Tertiary Endpoint: C-SSRS
Endpoint: Change from baseline in C-SSRS.
•
Analysis time points: Scheduled time points in the SoA.
•
Analysis population: FAS.
•
Analysis methodology: Number and percentage of subjects in each category at each 
visit using the C-CASA categories.  
Reporting results:
•
Descriptive data: The number and percentage of subjects in each category at baseline 
and post-baseline visits will be presented for each treatment arm. For subjects who 
have the wrong version of C-SSRS at the baseline assessment, C-SSRS at screening 
will be used as baseline. 
Figure:
•
Frequency plot for C-SSRS mapped to C-CASA.
6.1.3.15. Tertiary Endpoint: Hospital Anxiety and Depression Scale
Endpoint: Change from baseline in HADS.
•
Analysis time points: Scheduled time points in the SoA.
•
Analysis population: FAS.
CCI


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
Analysis methodology: Descriptive scores at each time point for anxiety sub-scale 
and depression subscale by treatment arms. The number and percentage of subjects 
with anxiety and depression sub scales score 0 to <8 (normal); 8 to <11 (mild); ≥11 to 
<15 (moderate); ≥15 (severe) at each time point by treatment arms.
Reporting results:

A summary table of descriptive statistics will be provided. 
The HADS scoring manual will be provided separately. 
6.1.3.16. Tertiary Endpoint: Target Lesion Assessments for Stable Vitiligo and for 
Segmental Vitiligo, if any 
Endpoint: Depigmentation rate of targeted lesions.

Analysis time points: Baseline and Week 24. 

Analysis population: FAS.

Analysis methodology: Number and percentage of lesions in each depigmentation 
category by active, stable and/or segmental vitiligo lesion status.  
Reporting results:

Descriptive data: The number and percentage of lesions in each depigmentation 
category at baseline and post-baseline visits will be presented for each treatment arm
and by stable vitiligo lesion and/or segmental vitiligo lesion status.

Number and percent of lesions by lesion type (active, stable, or segmental) at 
baseline.
6.1.3.17. Tertiary Endpoint: Dermoscopy
Endpoint: Number of lesions with less than 30% of white hair in the depigmented lesion.

Analysis time points: Scheduled time points in the SoA.

Analysis population: FAS.

Analysis methodology: Mean and standard deviation of number of fields with less 
than 30% of white hair.  
Reporting results:

Descriptive data: The number and percentage of subjects in each category at baseline 
and post-baseline visits will be presented for each treatment arm.






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6.1.5. Safety Summaries and Analyses
6.1.5.1. Adverse Events
It should be recognized that most studies are not designed to reliably demonstrate a causal 
relationship between the use of a pharmaceutical product and an AE or a group of AEs.
Except for select events in unique situations, studies do not employ formal adjudication 
procedures for the purpose of event classification. 
The TEAEs by system organ class and preferred term will be generated for the Induction 
Phase, Maintenance Phase, and Dose Ranging Period for both all-causality and 
treatment-related AEs. The SAEs (both all causality and treatment-related) by system organ 
class and preferred term may also be generated for Induction Phase, Maintenance Phase, and 
Dose Ranging Period as needed.
6.1.5.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the sponsor 
reporting standards.  Baseline is as defined in Section 3.6.2. In addition the incidence of 
specific clinical laboratory abnormalities including, but not limited to, anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid profile, and LFTs. 
The following laboratory abnormalities require re-testing within 1 week until resolution or 
agreement with sponsor.
Table 4.
Laboratory Re-Testing Criteria
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil 
Count
<2000/mm3 (2.0 x 109/L)
Hemoglobin
<9.0 g/dL
Platelet count
<100,000/mm3 (100 x 109/L)
Lymphocytes
<600/mm3 (< 0.6 x 109/L)
Chemistry
CK
>3x ULN (This also triggers urine myoglobin.)


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Laboratory values meeting the following criteria will be summarized by number and percent.
Table 5.
Laboratory Abnormality Criteria
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil 
Count
<1000/mm3 (<1.0 x 109/L)
Hemoglobin
<8.0 g/dL (<4.96 mmol/L; <80 g/L)
Platelet count
<75,000/mm3 (<75.0 x 109/L)
Lymphocytes
<500/mm3 (<0.5 x 109/L)
Chemistry
AST
>2.5x ULN
ALT
>2.5x ULN
Total bilirubin
>1.5x ULN
CK
>10x ULN
6.1.5.3. Vital Signs
Absolute values and change from baseline in systolic and diastolic BP, respiratory rate, pulse 
rate and temperature will be summarized by treatment and time post-dose, according to 
sponsor reporting standards.  
6.1.5.4. Electrocardiogram
Categorical summary tables will be summarized by treatment and time post-dose using 
sponsor reporting standards. A listing of ECG comments on findings and normal/abnormal 
results will be provided. 
6.1.5.5. Physical Examination
All physical exam data will be provided in the listings.
6.2. Analyses and Summaries During Extension Period
At Week 16 of the Dose Ranging Period, subjects will be evaluated for eligibility to enter the
Extension Period and be assigned to one of the treatment groups at Week 24. If due to 
COVID-19, the Week 16 visit of Dose Ranging Period is missing, the Week 12 or Week 20
Visit value will be used for Extension Period mapping. 
An unblinded programmer and unblinded study manager, independent from the blinded study 
team, will perform the response status calculation and group mapping for the Extension 
Period. The subjects, investigators, and individuals from the sponsor (or designee) who 
interact with the investigators and monitor safety will continue to be blinded to individual 
study treatments throughout the Extension Period of the study.
Figure 4 lists the routes subjects may experience. 




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Non-responders from 200-50 mg, 100-50 mg, or 50 mg arm in Dose Ranging period who:

Agree with nbUVB consent and agree with additional contraception methods -- will 
be allocated to Group 1. After Group 1 caps, they will be allocated to Group 2; after
Group 2 caps, they will be allocated to Group 3. 

Agree with nbUVB consent and do not agree with additional contraception methods -
- will be allocated to Group 2; after Group 2 caps, they will be allocated to Group 3. 

Do not agree with nbUVB consent and agree with additional contraception methods --
will be allocated to Group 1. After Group 1 caps, they will be allocated to Group 3.

Do not with nbUVB consent and do not agree with additional contraception methods 
-- will be allocated to Group 3.
Non-Responders from 30 mg arm in Dose Ranging period who:

Agree with additional contraception methods -- will be allocated to Group 1. After 
Group 1 caps, they will be allocated to Group 3. 

Do not agree with additional contraception methods -- will be allocated to Group 3. 
Non-Responders from 10 mg or Placebo arm who:

Agree with nbUVB consent -- will be allocated to Group 2. After Group 2 caps, then 
subjects will be allocated to Group 3.

Do not agree with nbUVB consent -- will be allocated to Group 3.
Group 1 and Group 2 will be capped at 60 subjects each. 
In general, for efficacy endpoints, analyses and summaries will be presented by visit and 
group. 
For safety endpoints and pharmacodynamics endpoints, analyses and summaries will be 
presented by visit and treatment. For safety endpoints, Baseline will be the same as the 
baseline in Dose Ranging Period. For pharmacodynamics endpoints, Baseline will be 
Week 24 of Dose Ranging Period (or the previous non missing visit if Week 24 visit is 
missing).
The only exception where the baseline definition differs from above are for Cystatin C and 
Cystatin C-based eGRF in Extension Group 1, which use the last measurement prior to first 
dose of PF-06700841 for baseline.


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6.2.1. Primary Endpoints (Safety)
Safety summary tables will be produced to evaluate potential risks associated with the safety 
and tolerability of the study medication. All clinical AEs, SAEs, TEAEs, as well as 
discontinuations due to AEs, will be summarized with frequency and percentage. 
Continuous outcomes (eg, vitals, safety lab parameters, etc.) will be summarized using n, 
mean, median, SD, etc.
Baseline will be the same as the baseline in Dose Ranging Period. Percent change from 
baseline on selected safety endpoints such as hemoglobin, absolute neutrophil count, platelet 
count, lymphocytes, creatine phosphokinase, lipid profile, and LFTs may be summarized.  
Subject listings may also be produced for these safety endpoints. The safety endpoints will be 
listed and summarized in accordance with Pfizer Data Standards. Detailed methodologies of 
these analyses are the same as those described in Section 6.1.5 for the analysis during Dose 
Ranging Period.
6.2.2. Exploratory Efficacy Analysis
Central read facial-VASI assessments performed in the Extension Period will be analyzed in 
the same manner as the site assessment facial-VASI analyses described below for continuous
and binary endpoints.
Two categories of analyses will be performed as part of the exploratory efficacy analyses for 
the continuous and binary endpoints in the extension period:
1. The first set of analyses will assess the long term effect of PF-06651600 for subjects 
enrolled in Extension Group 3. These analyses include all subjects in Extension 
Group 3 who received at least one dose of PF-06651660 during the extension period
(ie, extension analysis set group 3). Baseline will be Day 1 of the dose-ranging
period, and all post-baseline visits up to Week 24 of the extension period will be 
included. 
2. The second set of analyses will assess the effect of the add-on nbUVB therapy with 
PF-06651660 (ie, compare extension Groups 2 and 3). These analyses include all 
subjects in Extension Group 2 or 3 who received at least one dose of PF-06651660 
during the extension period (ie, extension analysis set Group 2/3). Baseline will be 
Day 1 of the extension period (or the previous non-missing visit), and all 
post-baseline visits up to Week 24 of the extension period will be included.
6.2.2.1. Continuous Endpoints
For all extension groups, Baseline will be Week 24 of Dose Ranging Period (or the previous 
non missing visit if Week 24 visit is missing) or Day 1 of the dose ranging period as 
explained in Section 6.2.2 for the two sets of analyses.
Endpoints: 

Percent change from baseline in VASI, site assessment facial-VASI, VES, and 
SA-VES.


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
Change from baseline in VASI, site assessment facial-VASI, and VES.

Change from baseline in VitiQoL, DLQI, EQ-5D-5L, HCRU, C-SSRS, and HADS.
Analysis time points: Scheduled time points in the SoA.
Analysis population: Extension analysis set.
Analysis methodology:

Summary statistics may be provided by treatment group and time point in the
Extension Period.

The following four endpoints will be analyzed at Extension Week 24 using the same 
ANCOVA model as in the primary analysis (Section 6.1.1.1): Percent change from 
baseline VASI, percent change from baseline site assessment facial-VASI, change 
from baseline VASI, change from baseline site assessment facial-VASI.

The following two endpoints may additionally be analyzed using the same MMRM 
model as described in the sensitivity analysis for the primary endpoint
(Section 6.1.1.2.2): Percent change from baseline VASI, percent change from 
baseline site assessment facial-VASI.

The following seven endpoints may be analyzed using a MMRM model 
(Section 5.2.2): change from baseline in VES, VitiQoL, DLQI, EQ-5D-5L, HCRU, 
C-SSRS, and HADS.
Reporting results: 

Descriptive data: n, mean, SD, median, min, and max at baseline and post-baseline 
visits will be presented.

Percent change from baseline: n, mean, SD, median, min and max will be presented. 
The LS means, 2-sided 90% CI for the LS means, difference between the LS means 
for each treatment by visit and the corresponding 2-sided 90% CI will also be 
presented.
Figures:

LS mean change from baseline and corresponding 2-sided 90% CI by visit and by 
treatment reporting group.  
6.2.2.1.1. Extension Group 1 endpoints
An ANCOVA model will be performed for Extension Group 1. Baseline will be Week 24 of 
Dose Ranging Period (or the previous non missing visit if Week 24 visit is missing).


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Endpoints: 

Percent change from baseline in central read facial-VASI.
Analysis time points: Scheduled time points in the SoA.
Analysis population: Extension group 1 analysis set.
Analysis methodology:

Summary statistics may be provided by treatment group and visit in the Extension 
Period.

The following endpoint will be analyzed at Extension Week 24 and intervening visits 
during the extension period using the same ANCOVA model as in the primary 
analysis (Section 6.1.1.1): Percent change from baseline central read facial-VASI.
Reporting results: 

Descriptive data: n, mean, SD, median, min, and max at baseline and post-baseline 
visits will be presented.

Percent change from baseline: n, mean, SD, median, min and max will be presented, 
as well as the LS means and 2-sided 90% CI for the LS means.
6.2.2.2. Binary Endpoints
For all extension groups, Baseline will be Week 24 of Dose Ranging Period (or the previous 
non missing visit if Week 24 visit is missing) or Day 1 of the dose ranging period as 
explained in Section 6.2.2 for the two sets of analyses.
Endpoints: 

VASI 50/75/90/100 and site assessment facial-VASI 50/75/90/100.

Proportion of subjects achieving sIGA 0 or 1 and ≥2-point improvement.

Proportion of subjects achieving “much improved” or “very much improved” in 
PGIC-V.

Proportion of subjects achieving “a lot less noticeable” or “no longer noticeable” on 
VNS.
The following descriptions use VASI50 as an example. The analyses for all binary endpoints
except for VNS are identical.
Analysis time points: Scheduled time points in the SoA.
Analysis population: Extension analysis set.








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8. REFERENCES
1.
B7981019 protocol Amendment 5.
2.
Chan IS, Zhang Z. Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics. 1999;55(4):1202-1209. doi:10.1111/j.0006-
341x.1999.01202.x.
3.
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. Parametric modeling of 
narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo 
Area Scoring Index. Arch Dermatol. 2004;140(6):677-683. 
doi:10.1001/archderm.140.6.677.


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9. APPENDICES 
9.1. APPENDIX 1. Summary of Efficacy Analyses
9.1.1. APPENDIX 1.1. Brief Summary of Key Efficacy and PRO Analyses in the Dose 
Ranging Period
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Percent change from 
baseline in central 
read facial-VASI at 
Week 24
FAS
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None
Primary
Percent change from 
baseline in central 
read facial-VASI at 
Week 24 and at 
intermediate time 
points
FAS
MMRM
Treatment, Visit, 
Treatment*Visit, 
baseline central 
read facial-VASI, 
baseline central 
read 
facial-VASI*treat
ment, skin type
None
Sensitivity for 
Primary 
(Week 24) and 
Secondary
(intermediate 
time points)
Percent change from 
baseline in central 
read facial-VASI at 
Week 24 
FAS
ANCOVA
Treatment, 
baseline efficacy 
score, skin type, 
BSA, geographic 
region 
None
Sensitivity for 
Primary
Percent change from 
baseline in central 
read facial-VASI at 
Week 24 (with 
central read facial-
VASI as 3% BSA 
instead of 4%)
FAS
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None
Exploratory for 
Primary
Change from 
baseline in central 
read facial-VASI at 
Week 24
FAS
4-
parameter 
Bayesian 
Emax
model
See Section 6.1.1.4 None
Supportive for 
Primary
Central read and site 
assessment facial-
VASI 50/75/90/100
at Week 24 and at 
intermediate time 
points
FAS
Chan and 
Zhang’s 
exact test
None
Non-Respon
der 
Imputation
Key secondary 
(central read 
facial-VASI75 
at Week 24) and 
Secondary (all 
others)


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Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Percent change from 
baseline in VASI at 
Week 24
FAS
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None
Secondary
Change from 
baseline SA-VES at 
Week 24 and at 
intermediate time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SA-VES, 
baseline 
SA-VES*treatment
, skin type 
None
Secondary
VASI 50/75/90/100
at Week 24 and at 
intermediate time 
points
FAS
Chan and 
Zhang’s 
exact test
None
Non-Respon
der 
Imputation
Secondary
Change from 
baseline in VitiQoL 
total score at 
Week 24 and at 
intermediate time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline VitiQoL, 
baseline 
VitiQoL*treatment, 
skin type
None
Secondary
sIGA 0 or 1 and 
2-point or greater 
improvement
FAS
Chan and 
Zhang’s 
exact test
None
Non-Respon
der 
Imputation
Secondary
Change from 
baseline central read 
and site assessment 
facial-VASI at 
Week 24 and at 
intermediate time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline central 
read and site 
assessment 
facial-VASI, 
baseline central 
read and site 
assessment 
facial-VASI*treat
ment, skin type
None
Exploratory
Change from 
baseline VES at 
Week 24 and at 
intermediate time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline VES, 
baseline 
VES*treatment, 
skin type
None
Exploratory


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Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Change from 
baseline in DLQI 
score
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline DLQI, 
baseline 
DLQI*treatment, 
skin type
None
Exploratory
9.1.2. APPENDIX 1.2. Brief Summary of Key Exploratory Efficacy and PRO Analyses 
in the Extension Period
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Percent change 
from baseline in 
VASI at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None
Exploratory
Percent change 
from baseline in 
site assessment 
facial-VASI* at 
ExWeek 24
Extension 
analysis set
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None
Exploratory
Percent change 
from baseline in 
VES at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline VES, 
baseline 
VES*treatment, 
skin type
None
Exploratory
Percent change 
from baseline in 
SA-VES at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SA-VES, 
baseline 
SA-VES*
treatment, skin 
type
None
Exploratory


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Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Change from 
baseline in 
VASI at 
ExWeek 24
Extension 
analysis set
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None 
Exploratory
Change from 
baseline in site 
assessment 
facial-VASI at 
ExWeek 24
Extension 
analysis set
ANCOVA
Treatment, 
baseline efficacy 
score, skin type
None 
Exploratory
Change from 
baseline in 
VASI at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment*Visit, 
baseline VASI, 
baseline 
VASI*treatment, 
skin type
None 
Exploratory
Change from 
baseline in site 
assessment 
facial-VASI at 
ExWeek 24
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment*Visit, 
baseline site 
assessment facial-
VASI, baseline 
site assessment 
facial-
VASI*treatment, 
skin type
None 
Exploratory
Change from 
baseline in VES
at ExWeek 24 
and at 
intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline VES, 
baseline 
VES*treatment, 
skin type
None 
Exploratory
Change from 
baseline in 
VitiQoL at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline VitiQoL, 
baseline VitiQoL
*treatment, skin 
type
None 
Exploratory


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Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing 
Data
Imputation
Interpretation
Change from 
baseline in 
DLQI score at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline DLQI, 
baseline 
DLQI*treatment, 
skin type
None 
Exploratory
Change from 
baseline HADS 
score
Extension 
analysis set
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline HADS, 
baseline 
HADS*treatment, 
skin type
None
Exploratory
VASI 
50/75/90/100 at 
ExWeek 24 and 
at intermediate 
time points
Extension 
analysis set
Chan and 
Zhang’s 
exact test
None
None
Exploratory
Site 
assessment 
facial-VASI 
50/75/90/100 
at ExWeek 24 
and at 
intermediate 
time points*
Extension 
analysis set
Chan and 
Zhang’s 
exact test
None
None
Exploratory
sIGA 0 or 1 
and 2-point or 
greater 
improvement
Extension 
analysis set
Chan and 
Zhang’s 
exact test
None
None
Exploratory
* If central read facial-VASI is completed in the extension period, analyses may also be repeated using central 
read facial-VASI values.


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9.2. APPENDIX 2. Data Derivation Details
9.2.1. Appendix 2.1. Definition and Use of Visit Windows for Analysis 
The use of visit windows in reporting the Extension Period will be explained in detail in the 
programming plan for this study. The key is to ensure that the windowing algorithm 
accommodates the visits for the active patients in the Extension Period and the placebo 
patients when they enter the retreatment period.
Visit
Start Day
End Day
Visit 1 (Screening)
Day -28
Day -1
Visit 2 (Day 1, Week 0)
Day 1
Day 1
Visit 3 (Day 15, Week 2)
Day 9
Day 22
Visit 4 (Day 29, Week 4)
Day 23
Day 49
Visit 5 (Day 57, Week 8)
Day 50
Day 77
Visit 6 (Day 85, Week 12)
Day 78
Day 105
Visit 7 (Day 113, Week 16)
Day 106
Day 133
Visit 8 (Day 141, Week 20)
Day 134
Day 161
Visit 9 (Day 169, Week 24)
Day 162
Day 189
Visit 10 (Day 170, ExD1) Group 2 
only
Day 162
Day 178
Visit 11 (Period Day 1, ExW4) 
Group 1 only
Period Day 1
Period Day 1
Visit 11 (Day 184, ExW2)
Groups 2, 3, 4, and 5
Day 179
Day 192
Visit 12 (Period Day 15, ExW6) 
Group 1 only
Period Day 2
Period Day 21
Visit 12 (Day 198, ExW4)
Groups 2, 3, 4, and 5
Day 193
Day 218
Visit 13 (Period Day 29, ExW8) 
Group 1 only
Period Day 22
Period Day 49
Visit 13 (Day 226, ExW8)
Groups 2, 3, 4, and 5
Day 219
Day 246
Visit 14 (Period Day 57, ExW12) 
Group 1 only
Period Day 50
Period Day 77
Visit 14 (Day 254, ExW12)
Groups 2, 3, 4, and 5
Day 247
Day 274
Visit 15 (Period Day 85, ExW16) 
Group 1 only
Period Day 78
Period Day 105
Visit 15 (Day 282, ExW16)
Groups 2, 3, 4, and 5
Day 275
Day 302
Visit 16 (Period Day 113, ExW20) 
Group 1 only
Period Day 106
Period Day 133
Visit 16 (Day 310, ExW20)
Groups 2, 3, 4, and 5
Day 303
Day 330
Visit 17 (Period Day 141, ExW24) 
Group 1 only
Period Day 134
Period Day 161


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Visit
Start Day
End Day
Visit 17 (Day 338, ExW24)
Groups 2, 3, 4, and 5
Day 331
Day 358
Visit 18 (Day 366, Follow-Up 
Visit 1)
Day 359
Day 386
Visit 19 (Day 394, End of Study 
Visit)
Day 387
Day 414


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9.3. APPENDIX 3. Statistical Methodology Details of Delta Method
It is known that the estimate and CI on the logit scale can be obtained using the SAS
GLIMMIX procedure with dist=binary and link=logit; using ilink option in GLIMMIX will 
generate the estimate for proportions. The variance of RD (proportion difference) cannot be 
directly obtained by GLIMMIX procedure using link=logit. This appendix describes how to 
obtain the estimate and the CI for RD (proportion difference) by the delta method.


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9.4. APPENDIX 4. Details on C-SSRS Mapping


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9.5. APPENDIX 5. Facial Vitiligo Area Scoring index (facial-VASI) -  Site Assessment
The facial VASI will be assessed by the Investigator. The local read facial VASI is 
calculated using a formula that is similar to facial-VASI central read.  It includes contribution 
from face (possible range, 0.00 to 4.00).  Scalp, neck, eyebrows, eyelashes, and vermilion 
will be excluded from this calculation, although total VASI assessment includes all of these 
regions.
Facial VASI = Digit Units × Depigmentation × 0.1
The volar surface of one digit (the subject’s thumb) is approximately 0.1% of the total body 
surface area and is used as a guide to estimate the baseline percentage of vitiligo involvement 
of face. 
The extent of depigmentation is expressed by the following percentages: 0, 10%, 25%, 50%, 
75%, 90%, or 100%.  

100% depigmentation: no pigment is present;

90% depigmentation: specks of pigment are present;

75% depigmentation: the depigmented exceeds the pigmented area;

50% depigmentation: the depigmented and pigmented areas are equal;

25% depigmentation:  the pigmented area exceeds the depigmented area; and 

10% depigmentation: only specks of depigmentation are present. 


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9.6. APPENDIX 6. Analysis of Change from Baseline VitiQoL scores
VitiQoL total score is calculated as sum of items 1-15 if no items are missing. If any items 
are missing, use the sum of the domain scores for the Total Score if all three domains have a 
computed score. The analysis method for the VitiQoL total score will be the same as the 
analysis used for MMRM sensitivity analysis for the primary endpoint (see
Section 6.1.1.2.2). Three domain scores will be analyzed using the same method as for 
VitiQoL total score: Participation Limitation (sum of items 3, 4, 6, 9, 10, 11, 14), Stigma 
(sum of items 1, 2, 5, 7, 15), and Behaviors (sum of items 8, 12, 13). If any item is missing 
but at least ½ of the domain items are non-missing (no more than 3, 2, or 1, respectively, for 
Participation Limitation, Stigma, or Behaviors), use the average of the domain’s non-missing 
as the missing item’s raw score and add all 7, 5 or 3 domain items scores to make the 
respective Domain score.
VitiQoL item 16, PGIS-V, will be summarized with frequency counts by each category of 
PGIS-V (0-6) at baseline and at Week 24. The proportion of subjects achieving 
improvement in each treatment group will be compared using a Fisher’s exact test for 
categories worsening (>0), no change, 1-point improvement, and ≥2-point improvement.