Conditions: Alopecia Areata
Keywords: Phase 2 randomized double-blind placebo alopecia areata safety efficacy JAK janus kinase moderate severe
Allocation: RANDOMIZED | Intervention model: 
Enrollment: 142
Healthy volunteers: no

Brief summary:
This is a Phase 2a, randomized, double blind, parallel group, multicenter study with an extension period. The study will have a maximum duration of approximately 113 weeks. This includes an up to 5 weeks Screening Period, a 24 week Treatment Period, a 4 week Drug Holiday (#1), an up to 12 month Single Blind (investigator open, sponsor open and subject blind) Extension Period, a 4 week drug holiday (#2), a 6 month Cross Over Open Label Extension Period and a 4 week Follow up Period.

Detailed description:

Arms:
arm 1: PF-06651600 arm 2: PF-06700841 arm 3: placebo

Interventions: intervention 1: PF-06651600 intervention 2: PF-06700841 intervention 3: Placebo
Intervention descriptions: intervention 1: 200 mg QD during induction and 50 mg QD during Maintenance intervention 2: 60 mg QD during induction and 30 mg QD during maintenance intervention 3: Placebo

Protocol document:
Prot_000.pdf: 
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A PHASE 2A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY 
PROFILE OF PF-06651600 AND PF-06700841 IN SUBJECTS WITH MODERATE 
TO SEVERE ALOPECIA AREATA WITH A SINGLE-BLIND EXTENSION 
PERIOD AND A CROSS-OVER OPEN LABEL EXTENSION PERIOD 
Investigational Product Number:
PF-06651600; PF-06700841
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2016-004048-13
Protocol Number:
B7931005
Phase:
2a
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 4
06 June 2018

In the Title, Schedule of Activities, Section 2 
Study Objectives and Endpoints, Section 3 Study 
Design, Section 6 Study Procedures, and 
Section 9 Data Analysis, added a 4-week Drug 
Holiday Period #2 and a 6-month Cross-Over 
Open Label Extension Period for subjects who 
complete the segment for non-responder in 
Single-Blind Extension Period. 
Rationale: The objective of the 6 months 
Cross-Over Open Label Extension Period is to 
provide opportunity for non-responders to one 
active study treatment to receive the opposite 
active study treatment.

In the Title, Schedule of Activities, Section 2 
Study Objectives and Endpoints, Section 3 Study 
Design, Section 6 Study Procedures, and 
Section 9 Data Analysis, changed the Extension 
Period to Single-Blind Extension Period
including a segment for non-responder and a 
Withdrawal/Retreatmetn segment for responder 
and included general ouline of the interim CSR. 
Rationale: Due to lack of clinical research in the 
area of Alopecia Areata, there is a strong 
scientific rationale to summarize and share the 
results from the 24 week Treatment Period, as 
that period of the study has been completed. 

In the Section 1 Introduction, mechanism of 
action of PF-06651600 is updated.
Rationale: Based on the new pre-clinical work, 
mechanism of action of PF-06651600 is updated.

In the Section 1.2 Background and Rationale, 
added information from other studies that 
investigate PF-06651600 and/or PF-06700841 in 
different therapeutic areas.
Rationale: To provide updated information for 


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PF-06651600 and/or PF-06700841 in different 
therapeutic areas.

In the Section 8 Adverse Event Reporting, added 
a special safety concern, fetal cleft lip which was 
reported in study B7931004, a trial investigating 
PF-06700841 in psoriasis patients affecting a 
singleton pregnancy of a subject on concomitant 
medications including herbal supplement which 
carried a pregnancy warning.
Rationale: To include a special safety concern 
reported in Study B7931004, a trial investigating 
PF-06700841 in psoriasis patients.

In the Section 9.7 Data Monitoring Committee, 
IRC infomation is updated. 
Rationale: The committee will have completed 
its work and been dissolved once the database 
lock and data release occurs for the initial 
24-week Treatment Period and the study team 
becomes unblinded. Unblinded study team will 
continue monitoring of the safety of subjects in 
the study. 

In the Section 11 Data Handling and Record 
Keeping and Section 12.3 Subject information 
and Consent, new requirements are incorporated.
Rationale: To align with the EU General Data 
Protection Regulation (GDPR) the appropriate 
verbiage is incorporated in the protocol. 

Minor administrative changes and sentence 
revisions made throughout the document.
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.
Amendment 3
02 August 2017

In the Schedule of Activities, Section 2 Study 
Objectives and Endpoints, Section 3 Study 
Design, and Section 6 Study Procedures, added a
4-week Drug Holiday Period and an up to 
12 months Extension Period. 
Rationale: To provide opportunites for subjects 


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to receive additional study treatment as to date 
no medications approved for treatment of
alopecia areata. 

In the Schedule of Activities and Section 6 Study 
Procedures, added medical history at the 
Baseline Visit.
Rationale: Any adverse events occurred prior to 
first dosing should be reflected on the medical 
history. 

In the Schedule of Activities, Section 6 Study 
Procedures, and Section 7.4.2 Laboratory Tests, 
added urine myoglobin at Screening, Week 28 
and in case of CK >3x ULN. 
Rationale: Urine myoglobin is added to ensure 
subject safety is fully evaluated prior to study 
entry and monitored during the study.

In the Schedule of Activities and Section 6 Study 
Procedures, added instruction to provide and 
review dosing instruction. 
Rationale: Adding instruction to provide and 
review dosing instruction to prevent medication 
error and ensure patient safety.

Section 4.1 Inclusion Criteria, added SALT 
score 50 to inclusion criteria #5.
Rationale: To provide clarification of the 
definition of moderate to severe AA.

Section 4.2, Exclusion Criteria, added the 
following exclusions: subjects with CK 
>3x ULN and positive urine myoglobin.
Rationale: Subjects with elevated CK and positive 
urine myoglobin will be excluded from 
participation to ensure subject safety is fully 
evaluated prior to study entry.

Section 4.4, Lifestyle Requirements, added 
requirements for subjects to avoid excessive 
exercise during the study, especially within one 


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week prior to the scheduled study visits and 
maintain adequate hydration, if possible.
Rationale: to ensure subject safety is fully 
evaluated during the study.

Section 6 Study Procedures, added instructions
that IP should be administered from the previous 
container. 
Rationale: to provide clarification and to be 
consistent with IP manual. 

Section 9.6 Interim Analysis, updated the interim 
analysis time point from 24 weeks to 12 weeks.
Rationale: the interim analysis time point is 
updated based on results from an investigator 
initiated research investigating tofacitinib for
12 weeks.

Appendix 6 Guidelines for Subject Safety 
Monitoring and Discontinuation, added that 
subjects with lymphocytes less than 0.6 x 109 /L 
or CK >3x ULN will be re-tested. 
Rationale: Subjects who experience decreased 
lymphocytes less than 0.6 x 109 /L or CK 
>3x ULN will be monitored to further evaluate 
subject safety.

Appendix 6 Guidelines for Subject Safety 
Monitoring and Discontinuation, added that 
subjects with CK >10x ULN will be 
discontinued. 
Rationale: Subjects who experience elevated CK 
>10x ULN will be discontinued from the study 
to ensure subject safety.

Minor administrative changes and sentence 
revisions made throughout the document.
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.


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Amendment 2
17 February 2017

In the Schedule of Activities, Section 6 Study 
Procedures, and Section 7.3.5 Audiogram, added 
audiogram assessments at Week 12 Visit.
Rationale: To monitor for potential changes in 
hearing during study conduct. 

In the Schedule of Activities, Section 6 Study 
Procedures, and Section 7.4.2 Laboratory Tests, 
added serum cystatin C and cystatin C based 
eGFR at various time points.
Rationale: Serum cystatin C and cystatin C based 
eGFR assessed at additional time points to 
facilitate interpretability of any findings in 
individual subjects.

In the Schedule of Activities, Section 7.3.7.2
Creatinine, Cystatin C, and eGFR, 
Section 8.4.3 Potential Cases of Decreased 
eGFR, and Appendix 6 Guidelines for Subject 
Safety Monitoring and Discontinuation, removed 
statement that a creatinine increase above the 
ULN will trigger a reflex test for serum 
cystatin C in order to facilitate both serum 
cystatin C based, and serum creatinine based 
eGFR calculation.
Rationale:  Serum cystatin C and cystatin C based 
eGFR assessed at additional time points to 
facilitate interpretability of any findings in 
individual subjects.

In the Schedule of Activities, Section 6 Study 
Procedures, IGA is removed from the Screening 
Visit. 
Rationale: IGA is removed from the Screening 
Visit to ensure the overall hair growth will be 
evaluated at baseline and each follow-up visit(s). 

Section 4.2, Exclusion Criteria, added the 
following exclusions: subjects with active renal 
disease or recent kidney stones.
Rationale: Subjects with active renal disease or 


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recent kidney stones are excluded from 
participation to ensure subject safety is fully 
evaluated prior to study entry.

Section 4.2, Exclusion Criteria, modified the 
lymphocyte count for study entry. 
Rationale: The lymphocyte count is modified to 
ensure that subjects entering the study are not put 
at additional risk of experiencing CTCAE 
Grade 3 adverse events by entering the study with 
these laboratory values on the lower end of the 
normal range. 

Section 4.2, Exclusion Criteria, modified the 
eGFR for study entry. 
Rationale: The eGFR is modified to allow elderly 
subjects with lower age adjusted eGFR to enter 
the study. 

Section 4.4, Lifestyle Requirements, added 
requirements for subjects who undergo color 
application to their hair. 
Rationale: Subjects who undergo color 
application to their hair, it is recommended that 
the color application will be performed within one 
week prior to the scheduled study visits, if 
possible.  This will facilitate the consistency of 
SALT assessment.

Section 5.8.2 Prohibited Medications and 
Treatments and Appendix 2 Prohibited 
Concomitant Medications, excluded substrates 
of CYP3A.
Rationale:  Subjects receiving drugs that are 
substrates of CYP3A (simvastatin or simvastatin 
containing products) are excluded from 
participation in the study to limit any potential 
interactions with the investigational product.

Section 7.3.7.2 Creatinine, Cystatin C, and 
eGFR clarified that creatinine elevations above 
the ULN will be followed until resolution or 


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baseline.
Rationale: Creatinine levels above the ULN will 
be followed until resolution or baseline to monitor 
subject safety.

Section 7.5. 1 Severity of Alopecia Tool, added 
a sentence that male pattern alopecia scoring 
may be considered for final adjudication by 
alopecia areata expert(s).
Rationale: For any male subject, male pattern 
alopecia scoring may be considered for final 
adjudication by alopecia areata expert(s). The 
adjudication is needed to ensure the assessment of 
complete hair growth.

Section 9.6 Data Monitoring Committee, added a 
statement that the IRC will review accumulating 
renal safety data and may propose changes to the 
protocol as needed to ensure subject safety.
Rationale: Additional monitoring of safety data to 
ensure patients’ safety.

Appendix 6, Guidelines for Subject Safety 
Monitoring and Discontinuation, added that any 
clinically meaningful, treatment related decline 
in hearing from baseline will result in the subject 
being discontinued from treatment with 
investigational product.
Rationale: Subjects who develop a clinically 
meaningful, treatment related decline in hearing 
from baseline will be discontinued from treatment 
and to further evaluate subject safety.

Minor administrative changes and sentence 
revisions made throughout the document.
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.
Amendment 1
10 November 2016

In the Schedule of Activities, Section 6 Study 
Procedures, and Section 7.3.5. Audiogram, 
added audiogram assessments.


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Rationale: To monitor for potential changes in 
hearing between baseline (between Visit 1 and 
Visit 2 [inclusive]) and at the end of the study 
(between Visit 10 and Visit 12 [inclusive]).
•
In the Schedule of Activities and Section 6 Study 
Procedures, remove time requirement for PK on 
early termination visit. 
Rationale: Additional time requirement of PK is 
removed to clarify that only one sample for PK 
will be collected on early termination visit. 
 
 
 
 
 
•
In the Schedule of Activities, Section 2, Study 
Objectives and Endpoints, Section 6 Study 
Procedures,  
 
 
•
In the Schedule of Activities and Section 6 Study 
Procedures,  added lesional biopsy at W32.
Rationale: Lesional biopsy at W32 is added to 
help understand the post-treatment effect of 
investigational products in alopecia areata at
cellular and molecular level at W32.
•
Section 3 Study Design and Section 4.1, 
Inclusion Criteria, added definition for current 
episode of fixed hair loss.
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Rationale: Subjects with current episode of fixed 
hair loss ≤7 years will be enrolled to study. 
Subjects with waxing and waning hair loss
pattern have no limitation. 
•
Section 7.8, Photography of Alopecia Areata 
Treated with Study Drug, added photographs of 
 
 
 
•
Appendix 2, Prohibited Concomitant 
Medications, added strong P-gp inhibitors and 
substrates of MDRI (eg, digoxin), OCT2 or 
MATE (dofetilide).
Rationale: Subjects receiving strong P-gp 
inhibitors and drugs that are substrates of MDRI 
(eg, digoxin), OCT2 or MATE (dofetilide) are 
excluded from participation in the study to limit 
any potential interactions with the investigational 
product.
•
Minor administrative changes and sentence 
revisions made throughout the document.
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.
Original 
protocol
29 August 2016
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...................................................................................................................17
APPENDICES .........................................................................................................................18
PROTOCOL SUMMARY.......................................................................................................19
SCHEDULE OF ACTIVITIES................................................................................................34
1. INTRODUCTION ...............................................................................................................48
1.1. Mechanism of Action/Indication.............................................................................48
1.2. Background and Rationale ......................................................................................48
1.2.1. Drug Development Rationale .....................................................................48
1.2.2. Study Background ......................................................................................49
1.2.3. Non-Clinical Pharmacokinetics and Metabolism.......................................50
1.2.3.1. Non-Clinical Pharmacokinetics and Metabolism of 
PF-06651600 .....................................................................................50
1.2.3.2. Non-Clinical Pharmacokinetics and Metabolism of 
PF-06700841 .....................................................................................50
1.2.4. Safety Data..................................................................................................51
1.2.4.1. Non-Clinical Safety...................................................................51
1.2.4.2. Clinical Experience ...................................................................54
1.2.5. Study Rationale...........................................................................................62
1.2.5.1. PF-06651600 Dose Rationale....................................................64
1.2.5.2. PF-06700841 Dose Rationale....................................................65
1.2.6. Summary of Benefits and Risks .................................................................66
1.2.7. Additional Information ...............................................................................66
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................67
2.1. Study Objectives and Endpoints During Treatment Period ....................................67
2.2. Study Objectives and Endpoints during Single-Blind Extension Period ................69
2.3. Study Objectives and Endpoints during Cross-Over Open Label Extension 
Period.........................................................................................................................71
3. STUDY DESIGN.................................................................................................................73
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................79
4.1. Inclusion Criteria.....................................................................................................79
4.2. Exclusion Criteria....................................................................................................80
4.3. Randomization Criteria ...........................................................................................86


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4.4. Lifestyle Requirements ...........................................................................................86
4.4.1. Contraception..............................................................................................87
4.5. Sponsor’s Qualified Medical Personnel..................................................................88
5. STUDY TREATMENTS.....................................................................................................88
5.1. Allocation to Treatment ..........................................................................................89
5.2. Breaking the Blind ..................................................................................................89
5.3. Subject Compliance.................................................................................................89
5.4. Investigational Product Supplies.............................................................................90
5.4.1. Dosage Form(s) and Packaging..................................................................90
5.4.2. Preparation and Dispensing........................................................................90
5.5. Administration.........................................................................................................90
5.6. Investigational Product Storage ..............................................................................91
5.7. Investigational Product Accountability...................................................................92
5.7.1. Destruction of Investigational Product Supplies ........................................92
5.8. Concomitant Treatment(s).......................................................................................92
5.8.1. Permitted Concomitant Medications ..........................................................92
5.8.2. Prohibited Medications and Treatments .....................................................93
5.8.3. Vaccinations ...............................................................................................94
6. STUDY PROCEDURES .....................................................................................................94
6.1. Screening.................................................................................................................94
6.2. Study Period ............................................................................................................96
6.2.1. Visit 2, Day 1..............................................................................................96
6.2.2. Visit 3, Day 15/Week 2 (2 days) ..............................................................97
6.2.3. Visit 4, Day 29/Week 4 (2 days) ..............................................................98
6.2.4. Visit 5, Day 43/Week 6 (3 days) ..............................................................99
6.2.5. Visit 6, Day 57/Week 8 (3 days) ............................................................100
6.2.6. Visit 7, Day 85/Week 12 (3 days) ..........................................................101
6.2.7. Visit 8, Day 113/Week 16 (3 days) ........................................................102
6.2.8. Visit 9, Day 141/Week 20 (3 days) ........................................................103
6.2.9. Visit 10, Day 169/Week 24/End of Treatment (3 days).........................103
6.2.10. Early Termination Visit..........................................................................105
6.3. Drug Holiday #1....................................................................................................106


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6.4. Extension Periods..................................................................................................106
6.4.1. Single-Blind Extension Period .................................................................106
6.4.1.1. Visit 11, Week 28 (3 days)....................................................106
6.4.1.2. Visit 12, Week 30 (3 days)....................................................107
6.4.1.3. Visit 13, Week 32 (3 days)....................................................108
6.4.1.4. Visit 14, Week 34 (3 days)....................................................109
6.4.1.5. Visit 15, Week 36 (3 days)....................................................110
6.4.1.6. Visit 16, Week 40 (3 days)....................................................110
6.4.1.7. Visit 17, Week 44 (3 days)....................................................111
6.4.1.8. Visit 18, Week 48 (3 days)....................................................112
6.4.1.9. Visit 19, Week 52 (3 days)....................................................113
6.4.1.10. Active Treatment (AT) Period ..............................................114
6.4.2. Drug Holiday # 2 ......................................................................................121
6.4.3. Cross-Over Open Label Extension Period................................................122
6.4.3.1. Visit 29, Cross-Over Day 1 (COD1).......................................122
6.4.3.2. Visit 30, Cross-Over Week 2 (3 days) ..................................123
6.4.3.3. Visit 31, Cross-Over Week 4 (3 days) ..................................123
6.4.3.4. Visit 32, Cross-Over Week 6 (3 days) ..................................124
6.4.3.5. Visit 33, Cross-Over Week 8 (3 days) ..................................125
6.4.3.6. Visit 34, Cross-Over Week 12 (3 days) ................................126
6.4.3.7. Visit 35, Cross-Over Week 16 (3 days) ................................127
6.4.3.8. Visit 36, Cross-Over Week 20 (3 days) ................................127
6.4.3.9. Visit 37, Cross-Over Week 24/Cross-Over End of 
Treatment (3 days) ........................................................................128
6.5. Follow-up Period...................................................................................................129
6.5.1. Visit 38, Followup 1 .................................................................................129
6.5.2. Visit 39, End of Study Visit......................................................................130
6.5.3. Follow-up Contact ....................................................................................131
6.6. Subject Withdrawal/Early Termination ................................................................131
7. ASSESSMENTS................................................................................................................132
7.1. Pregnancy Testing.................................................................................................133


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7.3. Safety Assessments ...............................................................................................134
7.3.1. Vitals Signs...............................................................................................135
7.3.2. Medical History, Physical Exam, Height, and Weight.............................135
7.3.3. Chest Radiography....................................................................................136
7.3.4. Electrocardiogram.....................................................................................136
7.3.5. Audiogram ................................................................................................136
7.3.6. Tuberculosis Testing.................................................................................137
7.3.6.1. Interferon Gamma Release Assay (IGRA) Tuberculin Test ...137
7.3.6.2. Mantoux/Purified Protein Derivative (PPD) Tuberculin 
Skin Test..........................................................................................138
7.3.7. Special Safety Assessment .......................................................................138
7.3.7.1. Dermatological Events ............................................................138
7.3.7.2. Creatinine, Cystatin C, and estimates of Glomerular 
Filtration Rate (eGFR).....................................................................139
7.4. Clinical Laboratory Tests......................................................................................139
7.4.1. Blood Volume...........................................................................................139
7.4.2. Laboratory Tests .......................................................................................140
7.5. Efficacy Assessments............................................................................................142
7.5.1. Severity of Alopecia Tool (SALT)...........................................................142
7.5.2. Investigator Global Assessment (IGA).....................................................142
7.6. Psychological Assessments...................................................................................143
7.7. Patient Report Outcome (PRO).............................................................................143
7.7.3. Patient Health Questionnaire – 8 items (PHQ-8) .....................................144
7.7.4. Suicidal Behaviors Questionnaire-Revised (SBQ-R)...............................144
7.8. Photography of Alopecia Areata Treated with Study Drug ..................................144
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7.10.8. Shipment of Pharmacodynamic Samples ...............................................147
7.11. Skin Biopsies.......................................................................................................147
7.12. Rater Qualifications.............................................................................................148
8. ADVERSE EVENT REPORTING....................................................................................148
8.1. Requirements.........................................................................................................148
8.1.1. Additional Details On Recording Adverse Events on the CRF................149
8.1.2. Eliciting Adverse Event Information........................................................150
8.1.3. Withdrawal from the Study Due to Adverse Events (see also the 
Subject Withdrawal/Early Termination section) ...........................................150
8.1.4. Time Period for Collecting AE/SAE Information....................................150
8.1.4.1. Reporting SAEs to Pfizer Safety.............................................150
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF ...............150
8.1.5. Causality Assessment ...............................................................................151
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................151
8.2. Definitions.............................................................................................................151
8.2.1. Adverse Events.........................................................................................151
8.2.2. Abnormal Test Findings ...........................................................................152
8.2.3. Serious Adverse Events ............................................................................152
8.2.4. Hospitalization..........................................................................................153
8.3. Severity Assessment..............................................................................................154
8.4. Special Situations ..................................................................................................154
8.4.1. Protocol-Specified Serious Adverse Events.............................................154
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8.4.2. Potential Cases of Drug-Induced Liver Injury..........................................154
8.4.3. Potential Cases of Decreased eGFR .........................................................156
8.4.4. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................157
8.4.4.1. Exposure During Pregnancy....................................................157
8.4.4.2. Exposure During Breastfeeding ..............................................159
8.4.4.3. Occupational Exposure ...........................................................159
8.4.5. Medication Errors .....................................................................................159
8.4.5.1. Medication Errors....................................................................159
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................160
9.1. Sample Size Determination...................................................................................160
9.2. Efficacy Analysis During the Treatment Period ...................................................161
9.2.1. Analysis of the Primary Endpoint During the Treatment Period .............161
9.2.2. Analysis of Secondary Endpoints During the Treatment Period..............161
9.2.3. Analysis of Other Endpoints During the Treatment Period......................162
9.2.3.1. Pharmacokinetic Analysis During the Treatment Period........162
9.2.3.2. PK/PD Unblinding Plan ..........................................................162
9.3. Safety Analysis During the Treatment Period.......................................................163
9.4. Analysis During the Single-Blind Extension Period and Cross-Over Open 
Label Extension Period............................................................................................164
9.4.1. Exploratory Efficacy Analysis During the Single-Blind Extension 
Period.............................................................................................................164
 
9.4.4. Safety Analysis for Single-Blind Extension Period and Cross-Over 
Open Label Extension Period ........................................................................165
9.5. Interim Analysis During the Treatment Period.....................................................166
9.6. Data Monitoring Committee .................................................................................166
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................167
11. DATA HANDLING AND RECORD KEEPING ...........................................................167
11.1. Case Report Forms/Data Collection Tools/Electronic Data Record...................167
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11.2. Record Retention.................................................................................................168
12. ETHICS............................................................................................................................169
12.1. Institutional Review Board/Ethics Committee....................................................169
12.2. Ethical Conduct of the Study ..............................................................................169
12.3. Subject Information and Consent........................................................................169
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................170
13. DEFINITION OF END OF TRIAL.................................................................................170
13.1. End of Trial in a Member State...........................................................................170
13.2. End of Trial in All Other Participating Countries...............................................170
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................171
15. PUBLICATION OF STUDY RESULTS........................................................................171
15.1. Communication of Results by Pfizer ..................................................................171
15.2. Publications by Investigators ..............................................................................172
16. REFERENCES ................................................................................................................173
LIST OF TABLES
Table 1.
Skin and Subcutaneous Tissue Disorder Occurrence ...........................................55
Table 2.
Summary of Plasma PF-06651600 Pharmacokinetic Parameters Following 
Single Oral Doses, Study B7981001 ....................................................................56
Table 3.
Summary of Steady State Plasma and Urine PF-066651600 
Pharmacokinetic Parameters Following Multiple Dose Administration, 
Study B7981001 ...................................................................................................57
Table 4.
Summary of Plasma PF-06700841 Pharmacokinetic Parameters Following 
Single Oral Doses, Study B7931001 ....................................................................61
Table 5.
Summary of Steady State Plasma and Urine PF-06700841 Pharmacokinetic 
Parameters Following Multiple Dose Administration, Study B7931001.............62
Table 6.
Summary of Predicted Steady State Plasma PF-06651600 Pharmacokinetic 
and Pharmacodynamic Parameters.......................................................................64
Table 7.
Summary of the Predicted In Vitro Average Percent Signaling Inhibition 
Based on Steady State Pharmacokinetics of PF-06651600..................................65
Table 8.
Summary of Predicted Steady State Total Plasma PF-06700841 
Pharmacokinetic and Pharmacodynamic Parameters ...........................................65
Table 9.
Investigator Global Assessment (IGA) Score.....................................................142


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 18
APPENDICES
Appendix 1. Abbreviations....................................................................................................177
Appendix 2. Prohibited Concomitant Medications................................................................182
Appendix 3. Severity of Alopecia Tool (SALT) ...................................................................184
Appendix 4. Management of Dermatological Events............................................................187
Appendix 6. Guidelines for Subject Safety Monitoring and Discontinuation.......................189
Appendix 6.1. Monitoring......................................................................................................189
Appendix 6.2. Discontinuation ..............................................................................................189
Appendix 9. Suicidal Behaviors Questionnaire-Revised (SBQ-R) .......................................198
Appendix 10. Patient Health Questionnaire – 8 items (PHQ-8)............................................200
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 19
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 critical for leukocyte activation, 
proliferation, survival and function. Cytokine receptors demonstrate restricted association 
with JAKs such that different receptors or receptor classes preferentially utilize a given JAK 
dimer combination to transduce their signal.  JAK1 pairs with JAK3 to mediate -common 
cytokine signaling and also with JAK2 or TYK2 to transmit the signals of additional 
cytokines important in inflammation and immune responses including interleukin (IL) -2, -4, 
-5, -6, -12, -13, -15, -21, -23, -31, interferon gamma (IFN), and interferon alpha (IFN).  
Following cytokine activation, receptor-associated JAKs are phosphorylated and in turn 
phosphorylate specific sites on the receptor intracellular domain.  Phosphorylation of specific 
sites on the intracellular domain of the receptor allows for the recruitment of signal 
transducers and activators of transcription (STATs) that can subsequently be phosphorylated 
by JAKs.16  Phosphorylated STAT molecules are released from the receptor, translocate to 
the nucleus where they bind to specific sites on the deoxyribonucleic acid (DNA) and 
regulate gene transcription.18  The tyrosine kinase expressed in hepatocellular carcinoma 
(TEC) kinase family consists of five members including TEC, Bruton’s tyrosine kinase 
(BTK), bone marrow-expressed kinase (BMX), inducible T-cell kinase (ITK) and resting 
lymphocyte kinase (RLK/TXK), that are primarily expressed in hematopoietic cells.  TEC 
kinases play an important role in antigen receptor signaling and BTK and ITK regulate the 
signal transduction pathways initiated by the activation of B cell receptor (BCR) and T cell 
receptor (TCR), respectively.31,27
PF-06651600 is an orally bioavailable small molecule that inhibits irreversibly JAK3 with 
selectivity over the other three JAK isoforms, JAK1, JAK2 and TYK2.  PF-06651600 also 
inhibits irreversibly the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase 
family (BTK, BMX, ITK, TEC, TXK), with high selectivity over the broader kinome. 
PF-06651600 inhibits the cytotoxic function of CD8+ T cells and NK cells which have been 
implicated in the pathogenic process of AA.34,30 This inhibition may be mediated through 
mechanisms dependent on JAK3 and TEC kinase family members.33,28,29 PF-06651600 also 
potently inhibits signaling of the JAK3-dependent receptors for IL-15 and IL-21, which have 
been implicated in the pathogenic pathways of AA.32
PF-06700841 is a dual TYK2/JAK1 inhibitor with a good selectivity profile over the other 
human kinases including JAK2.  TYK2/JAK1 are critical signaling kinases that regulate the 
signal transduction pathways triggered by several cytokines implicated in the pathogenesis of 
AA, including IFN, IL-2, IL-15, IL-12, and IL-23.4,25,6
Both compounds will be investigated in patients with AA. 


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 20
Objectives and Endpoints
Study Objectives and Endpoints during Treatment Period
Primary Objective:
Primary Endpoint:

To evaluate the efficacy of PF-06651600 and 
PF-06700841 compared to placebo at Week 24 in 
adult subjects with moderate to severe alopecia 
areata.

Change from baseline of Severity of Alopecia 
Tool (SALT) score at Week 24.
Secondary Objectives:
Secondary Endpoints:
Key Secondary Efficacy Objective: 

To evaluate the effect of PF-06651600 and 
PF-06700841 on SALT 30 at Week 24 in adult 
subjects with moderate to severe alopecia areata.
Key Secondary Efficacy Endpoint:

Proportion of subjects achieving a 30% 
improvement in SALT (SALT 30) at Week 24.  
Other Secondary Efficacy Objectives:

To evaluate the effect of PF-06651600 and 
PF-06700841 on additional efficacy endpoints 
over time in adult subjects with moderate to 
severe alopecia areata in the Treatment Period.
Other Secondary Efficacy Endpoints:

Change from baseline in Investigator Global 
Assessment (IGA) at all time points up to 
Week 24 as specified in the Schedule of 
Activities (SoA).

Change from baseline in SALT at intermediate 
time points up to Week 24 as specified in the 
SoA.

Proportion of subjects achieving a 30% 
improvement in SALT (SALT 30) at 
intermediate time points up to Week 24 as 
specified in the SoA except for Week 24. 

Proportion of subjects achieving a 50%, 75% 
and 100% improvement in SALT (SALT 50, 
SALT 75, and SALT 100) at all time points up
to Week 24 as specified in the SoA.

Percentage change in SALT from baseline to 
Week 24 at intermediate time points as 
specified in the SoA.
Safety Objectives:

To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time in 
adult subjects with moderate to severe alopecia 
areata in the Treatment Period.
Safety Endpoints:

Incidence of treatment-emergent adverse events 
(AEs) 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.


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 21
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 22
 
 
 
 
 
 
 
Study Objectives and Endpoints during Single-Blind Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time 
in adult subjects with moderate to severe 
alopecia areata during the Single-Blind 
Extension Period.
•
Incidence of treatment-emergent adverse events (AEs)
during the Single-Blind Extension Period.
•
Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
profile, and liver function tests (LFTs) during the 
Single-Blind Extension Period.
 
 
 
 
•
Change from baseline in SALT during the 
Single-Blind Extension Period at all time points as 
specified in the SoA.
•
Proportion of subjects achieving SALT 30 during the 
Single-Blind Extension Period at all time points as 
specified in the SoA.
•
Proportion of subjects achieving SALT 50, SALT 75, 
SALT 100 during the Single-Blind Extension Period 
at all time points as specified in the SoA.
 
 
•
Time to achieve the retreatment criteria during the 
Withdrawal/Retreatment part of the Extension Period 
among subjects who achieved primary endpoint at 
Week 24.
C
C
I
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C
C
I


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 23
•
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C
C
I
C
C
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 24
Study Objectives and Endpoints during Cross-Over Open Label Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time 
in subjects who are non-responders to 
PF-06700841 and PF-06651600, 
respectively, during the Cross-Over Open 
Label Extension period.
•
Incidence of treatment-emergent adverse events (AEs)
during the Cross-Over Open Label Extension period.
•
Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
profile, and liver function tests (LFTs) during the 
Cross-Over Open Label Extension Period.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 25
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C
C
I


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 26
Study Design Schematic
Placebo, n= 22*
Placebo, n=22*
PF-06651600, n =44
Screening
35 days
Induction
4 weeks
Maintenance 20 weeks
Biopsy Sub-study (selected sites)
Treatment Period only
PF-06700841, n= 44
60 mg
30 mg
200 mg
50 mg
* During the data analysis, the placebo groups will be combined in 
treatment period
Drug 
Holiday #1
4 weeks 
Placebo, n=22*
Treatment Period 
24 weeks


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 27
Cross-Over Open Label Extension Period schematic 
Sponsor open, investigator open, subject blind
# All subjects who complete the initial 24-week Treatment Period will be evaluated for potential entry into the Single-Blind Extension Period during the Drug Holiday #1.  Subjects 
will enter the Single-Blind Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s entrance in the 
Single-Blind Extension Period. Subjects will be assigned by the study designee(s) to receive either active treatment (PF-06651600 or PF-06700841) to start the segment of 
non-responder or placebo at Week 28 (after the 4-week Drug Holiday #1) to start the Withdrawal/Retreatment segment for responders. 
+ Subjects who are assigned to the placebo group will receive placebo for up to 24 weeks until they meet the retreatment criteria described in the SAP.  Subjects who meet the criteria 
will receive the same respective active compound (PF-06651600 or PF-06700841), dose, and treatment duration as the original treatment which consists of a 4-week induction 
period and a 20-week maintenance period, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation 
(audiogram result available within 8 weeks is acceptable).  Subjects who do not meet the retreatment criteria throughout the 24 weeks will be go directly to the EOS visit. Subjects 
who complete the Withdrawl/Retreatment segment will go directly to the Follow-up Period and will not participate Cross-Over Open Label Extension Period.
* Retreatment criteria will be described in the SAP.  The study designee(s), who are independent of the study team, will inform the site if the subject meets the  criteria to start active 
treatment, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation (audiogram result available within 
8 weeks is acceptable). 
Single-BlindExtension Period
EOS
Drug 
Holiday 
#1
4 weeks# 
N
Do not meet retreatment criteria 
throughout 24 weeks
Placebo+
Meets 
retreatment 
Criteria *
Y
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
segment for non-responder
Withdrawal/Retreatment segment for responders
FU
Period
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤66
Induction
4 weeks
Maintenance 20 weeks


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 28
Cross-Over Open Label Extension Period
PF-06651600
non responder
PF-06700841
non responder
Y
PF-06651600, n66
200 mg
50 mg
Induction
4 weeks
Maintenance 20 
weeks
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
Follow up 
4 weeks
N
*All subjects who are assigned to receive active treatment (PF-06651600 or PF-06700841) directly and complete the segment for non-responder in Single 
Blind Extension Period may be evaluated for potential entry into the Cross-Over Open Label Extension Period during the Drug Holiday #2.  Subjects will 
enter the Cross-Over Open Label Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Cross-Over Open Label Extension Period as well as the non-responder criteria is met at Week 52.  
Meet  non-
responder 
criteria? *
Drug 
Holiday 
#2 
4 weeks*


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 29
Study Design and Treatments:
Study B7931005 will investigate the JAK3 inhibitor PF-06651600 and TYK2/JAK1 inhibitor 
PF-06700841 in AA.  This is a Phase 2a, randomized, double-blind, parallel group, 
multicenter study with two extension periods. The study will have a maximum duration of 
approximately 113 weeks. This includes an up-to-5 weeks Screening Period, a 24-week 
Treatment Period, a 4-week Drug Holiday #1, an up to 12 months Single-Blind (sponsor 
open, investigator open and subject blind) Extension Period, a 4-week Drug Holiday #2, a 
6-month Cross-Over Open Label Extension Period and a 4 week Follow-up Period. The 
study will enroll a total of approximately 132 subjects.  The study will be conducted at 
approximately 30 to 40 sites.
Subjects who have moderate to severe alopecia areata (50% hair loss of the scalp [SALT 
score 50] and without evidence of hair regrowth within the previous 6 months; current 
episode of fixed hair loss 7 years) present at the screening and baseline visits will be 
included in the study.  Photographs will be taken at the Screening Visit to verify eligibility 
(50% hair loss of the scalp).  Subjects will be randomized to PF-06651600 or matching 
placebo in a 2:1 ratio or PF-06700841 or matching placebo in a 2:1 ratio in the initial 
Treatment Period.  During the data analysis, placebo groups will be combined to yield final 
investigational product: placebo ratios of 1:1:1 for each investigational product.  
Investigators, subjects, and the sponsor study team will be blinded as to treatment group.
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 in the interim CSR and published 
once the last subject last visit occurs for the initial 24-week Treatment Period. The interim 
study report may be shared with the principal investigator (PI) when it is available. 
Subjects will be screened within 35 days prior to the first dose of study drug to confirm that 
they meet the subject selection criteria for the study.  The 24-week treatment period consists
of a 4-week induction treatment period and a 20-week maintenance treatment period. 
An induction dose of 200 mg once daily (QD) for 4 weeks followed by maintenance dosing 
of 50 mg QD for 20 weeks of PF-06651600, an induction dose of 60 mg QD for 4 weeks 
followed by maintenance dosing of 30 mg QD for 20 weeks of PF-06700841, and matching 
placebo will be investigated. 
A biopsy sub-study will be performed at selected sites only during the initial Treatment 
Period of 24 weeks.  Approximately 42 subjects will be randomized (expected to provide 
approximately 30 completers).  Subjects will be randomized to PF-06651600 or matching 
placebo in a 2:1 ratio or PF-06700841 or matching placebo in a 2:1 ratio.  During the data 
analysis for the biopsy sub-study, placebo groups will be combined to yield final 
investigational product: placebo ratios of 1:1:1 for each investigational product. 


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 30
Single-Blind Extension Period
Alopecia Areata is a disease with high unmet medical need.  Currently there are no approved 
medications for treatment of AA.  An Extension Period has been added to this study to
evaluate additional safety and tolerability of PF-06651600 and PF-06700841. The Extension 
Period will become Single-Blind (investigator open, sponsor open and subject blind) upon 
approval of Amendment 4.
The Single-Blind Extension Period will provide an opportunity for subjects to receive 
additional active study treatment.  It will start after a 4-week Drug Holiday #1. The duration 
of the Single-Blind Extension Period can be up to 12 months.  Only subjects who complete 
Week 24 of the initial treatment period may be considered for eligibility to enter the 
Single-Blind Extension Period.  Subjects who discontinue during the initial treatment period 
will enter the 4-week Follow up Period and will not be eligible for the Single-Blind 
Extension Period. 
All subjects who complete the initial 24-week Treatment Period will be evaluated during 
Drug Holiday #1 for potential entry into the Single-Blind Extension Period.  After the 
4-week Drug Holiday #1, subjects will enter the Single-Blind Extension Period providing 
none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Extension Period.  Subjects who meet Exclusion 
criteria #9, #10, or #26 will be discontinued and enter the Follow-up Period.
At Week 28 (after the 4-week Drug Holiday #1 that follows completion of Week 24), 
subjects will be assigned by the study designee(s) to receive either active treatment 
(PF-06651600 or PF-06700841) to start the segment for non-responder or placebo to start the 
Withdrawal/Retreatment segment for responder. The detailed criteria for treatment 
assignment will be described in the statistical analysis plan (SAP). The study designee(s), 
who are independent of the study team, will provide the site with a treatment assignment 
when investigational product (IP) is being supplied via the IRT system post Week 24. A 
detailed communication plan will be provided to the site.  The probability to receive active 
treatment in the Single-Blind Extension Period is approximately 33% to 100%. During the 
Single-Blind Extension Period, all the subjects assigned to placebo at Week 28 will have a 
probability of 100% to receive active treatment if they meet the retreatment criteria outlined 
in the SAP. 
During the Single-Blind Extension Period, subjects who are assigned to the active treatment 
(PF-06651600 or PF-06700841) at Week 28 to start the segment for non-responder will 
receive the same respective active compound (PF-06651600 or PF-06700841), dose, and 
treatment duration ( a 4-week Induction Period and a 20-week Maintenance Period) as the 
original Treatment Period. 
Subjects who are assigned to the placebo group at Week 28 to start the 
Withdrawal/Retreatment segment will receive placebo for up to 24 weeks until they meet the 
retreatment criteria described in the SAP. These subjects will be assessed every 2 weeks 
during the first 8 weeks and then every 4 weeks up to 24 weeks by the study designee(s).


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 31
The study designee(s), who are independent of the study team, will inform the site if the 
subject meets the criteria to start active treatment. Subjects who meet the criteria will receive 
the same respective active compound (PF-06651600 or PF-06700841), dose, and treatment 
duration as the original treatment which consists of a 4-week induction period and a 20-week 
maintenance period, providing none of the Exclusion criteria #9, #10, and #26 are met and 
the audiogram result does not preclude patient’s participation (audiogram result available 
within 8 weeks is acceptable).  Subjects who meet Exclusion criterion #9, #10, or #26 will be 
discontinued from the Single-Blind Extension Period and will go directly to the end of study 
(EOS) visit.  Subjects who do not meet the retreatment criteria for initiation of active 
treatment throughout the 24 week period (Week 28 to Week 52) will go directly to the EOS 
visit. Subjects who complete the Withdrawal/Retreatment segment will go directly to the 
Follow-up Period and will not participate Cross-Over Open Label Extension Period.
Any subject that has completed the initial 24 weeks of the Protocol B7931005 prior to 
Amendment 3 availability is eligible for evaluation for potential enrollment into the 
Single-Blind Extension Period. Subjects are to be discussed with the sponsor for possible 
enrollment for the Single-Blind Extension Period.
Cross-Over Open Label Extension Period
A 24 week Cross-Over Open Label Extension Period has been added to this study to evaluate 
safety and efficacy of PF-06651600 and PF-06700841 in subjects who complete the segment 
for non-responder in Single-Blind Extension Period and did not respond to the initial active 
treatment. More specifically, subjects who are PF-06651600 non-responder at Week 52 will 
receive PF-06700841 in the Cross-Over Open Label Extension Period. Subjects who are
PF-06700841 non-responder at Week 52 will receive PF-06651600 in the Cross-Over Open 
Label Extension Period. The subjects who were responders at Week 52 will enter the 
Follow-up Period directly. Non-responders are defined as subjects who have not achieved 
30% improvement in SALT relative to the baseline of the Treatment Period at Week 52. 
All subjects who complete the segment for non-responder in Single-Blind Extension Period 
and are non-responders at Week 52 will be evaluated during the Drug Holiday #2 for 
potential entry into the Cross-Over Open Label Extension Period.  After the 4-week Drug 
Holiday #2, subjects will enter the Cross-Over Open Label Extension Period providing none 
of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude 
patient’s entrance in the Cross-Over Open Label Extension Period as well as the 
non-responder criteria is met at Week 52. Audiogram result available within 8 weeks is 
acceptable. Subjects who meet Exclusion criteria #9, #10, or #26 will enter the Follow-up 
Period directly. Subjects who do not meet the non-responder criteria at Week 52 will be 
informed by the study designee(s) during the Drug Holiday #2 and go directly to the 4-week 
Follow-up Period. Subjects who discontinue during the Single-Blind Extension Period will 
enter the 4-week Follow-up Period and will not be eligible for the Cross-Over Open Label
Extension Period. 


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 32
At Cross-Over Open Label Day 1 (after the 4-week Drug Holiday #2 that follows completion 
of Single-Blind Extension Period), non-responders will be assigned to receive either 
PF-06651600 or PF-06700841(the opposite of the assigned active treatment in the initial 
24 weeks and Single-Blind Extension Period). 
During the Cross-Over Open Label Extension Period, subjects will receive an induction dose 
of 200 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD for 20 weeks of 
PF-06651600 or an induction dose of 60 mg QD for 4 weeks followed by maintenance 
dosing of 30 mg QD for 20 weeks of PF-06700841. 
Any subjects who has completed the segment for non-responder in Single-Blind Extension 
Period prior to protocol Amendment 4 initiation at the investigator site is eligible for 
evaluation for potential enrollment into the Cross-Over Open Label Extension Period.  These 
subjects are to be discussed with the sponsor prior to any possible enrollment into the 
Cross-Over Open Label Extension Period.
Statistical Methods:
A comprehensive overall Statistical Analysis Plan (SAP) will be provided prior to the 
un-blinding of the trial.
The sample size is based on the primary efficacy endpoint, mean change from baseline in 
SALT score at Week 24.
All subjects who receive at least one dose of randomized study medication, and have a 
baseline and at least one post-baseline measurement (after taking randomized study 
medication) will be included in the efficacy data analyses.
The primary efficacy endpoint is change from baseline in the SALT score for the Treatment 
Period.  The primary time point is Week 24.
 
The safety analysis set will include all subjects who have received at least one dose of the 
study drug or placebo. 
Pharmacokinetic concentrations in treatment period will be summarized and presented with 
summary statistics and, if appropriate, non-compartmental pharmacokinetic (PK) parameter 
estimates will be provided. There will not be any PK assessments during the Single-Blind 
Extension Period.
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 12
visit. Additional interim analyses may be performed based on emerging data. 
 
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 33
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.  There will be a separate Internal Review Committee to
review the results of any interim analyses.  The committee will have completed its work and 
been dissolved once the database lock and data release occurs for the initial 24-week 
Treatment Period and study team becomes unblinded. Unblinded study team will continue 
monitoring of the safety of subjects in the study.


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 34
SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Protocol Activity 
Screening 
Period
Treatment Period
Drug Holiday
#1aa
Treatment Period
Induction Phase
Treatment Period
Maintenance Phase
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Visit Daya
Day -35 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 85
Day 113
Day 141
Day 169
Week
N/A
W2
W4
W6
W8
W12
W16
W20
W24
Visit Window
N/A
2 Days based on Day 1 visit
3 Days based on Day 1 visit
4 weeks
Enrollment procedure
Informed consent
X
Inclusion/Exclusion criteria
X
X
Xaa
Demographics 
X
Medical history and AA
disease historyc
X
X
Medical procedures
Complete physical 
examinationd
X
X
X
Targeted physical 
examinatione
X
X
X
X
X
X
X
Vital signsf
X
X
X
X
X
X
X
X
X
X
12-Lead ECGg
X
X
X
Heighth
X
Weighth
X
X
Chest radiographsi
X
Audiogramj
X
X
X
Laboratory
Hematology
X
X
X
X
X
X
X
X
X
X
Blood chemistry
X
X
X
X
X
X
X
X
X
X
Fasting lipid Panelk
X
X
X
Cystatin C (and eGFR)l
X
X
X
X
X
X
X
X
X


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 35
Protocol Activity 
Screening 
Period
Treatment Period
Drug Holiday
#1aa
Treatment Period
Induction Phase
Treatment Period
Maintenance Phase
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Visit Daya
Day -35 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 85
Day 113
Day 141
Day 169
Week
N/A
W2
W4
W6
W8
W12
W16
W20
W24
Visit Window
N/A
±2 Days based on Day 1 visit
±3 Days based on Day 1 visit
4 weeks
Urinalysism
X
X
X
X
X
X
X
X
X
X
Urine Myoglobindd
X
Serum FSH (WONCBP 
only) or serum pregnancy 
test (WOCBP)n
X
Urine pregnancy test
(WOCBP)o
X
X
X
X
X
X
X
X
X
HIV testingp
X
HBsAg, HBcAb, (HepB 
reflex testing), and 
HCVAbq
X
Tuberculosis testr
X
Viral Surveillance: EBV, 
CMV, HSV1, HSV2, and 
VZV
X
X
X
X
X
Laboratory 
Pharmacodynamics
IP-10 (CXCL10)
X
X
X
X
FACS-TBNK 
X
X
X
X
Immunoglobulins (total Ig, 
IgA, IgG, IgM)
X
X
X
IgE
X
X
X
 
Trial treatment
Impala registration
X
Randomization
X
Investigational product 
dispensing
X
X
X
X
X
X
X
X
Investigational product
administrations
X
→
→
→
→
→
→
→
X
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Final Protocol Amendment 4, 06 June 2018
Page 36
Protocol Activity 
Screening 
Period
Treatment Period
Drug Holiday
#1aa
Treatment Period
Induction Phase
Treatment Period
Maintenance Phase
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Visit Daya
Day -35 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 85
Day 113
Day 141
Day 169
Week
N/A
W2
W4
W6
W8
W12
W16
W20
W24
Visit Window
N/A
±2 Days based on Day 1 visit
±3 Days based on Day 1 visit
4 weeks
Investigational product
accountability
X
X
X
X
X
X
X
X
Clinical assessments
IGA
X
X
X
X
X
X
X
X
X
SALT
X
X
X
X
X
X
X
X
X
X
Photographt
X
X
X
X
X
X
X
X
Patient reported outcome
SBQ-Ru
X
PHQ-8u
X
 
 
 
 
 
Other
Prior and current 
concomitant Treatment(s)
x
→
→
→
→
→
→
→
→
→
Serious and non-serious 
adverse event monitoring
X
→
→
→
→
→
→
→
→
→
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Final Protocol Amendment 4, 06 June 2018
PFIZER CONFIDENTIAL
Page 37
Protocol Activity 
Screening 
Period
Treatment Period
Drug Holiday
#1aa
Treatment Period
Induction Phase
Treatment Period
Maintenance Phase
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Visit Daya
Day -35 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 85
Day 113
Day 141
Day 169
Week
N/A
W2
W4
W6
W8
W12
W16
W20
W24
Visit Window
N/A
2 Days based on Day 1 visit
3 Days based on Day 1 visit
4 weeks
Contraception check
X
X
X
X
X
X
X
X
X
X
Biopsy sub-study
Non-lesional biopsyy
X
Lesional biopsy for cellular 
and molecular analysesy
X
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Protocol Activity 
Single-Blind Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
11
12
13
14
15
16
17
18
19
Week
W28bb
W30
W32
W34
W36
W40
W44
W48
W52
Visit Window
±3 Days 
based on 
Day 1 visit
±3 Days based on W28 visit
Medical procedures
Complete physical examinationd
X
X
Targeted physical examinatione
X
X
X
X
X
X
X
Vital signsf
X
X
X
X
X
X
X
X
X
12-Lead ECGg
X
X
Weighth
Audiogramj
X
X
Laboratory
Hematology
X
X
X
X
X
X
X
X
X
Blood chemistry
X
X
X
X
X
X
X
X
X
Fasting lipid Panelk
X
X
X
Cystatin C (and eGFR)l
X
X
X
X
X
X
X
X
X
Urinalysism
X
X
X
X
X
X
X
X
X
Urine Myoglobindd
X
Urine pregnancy test (WOCBP)o
X
X
X
X
X
X
X
X
X
Viral Surveillance: EBV, CMV, HSV1, 
HSV2, and VZV
X
X
X
X
X
 
 
 
Trial treatment
Provide and review dosing instructions
X
X
X
X
X
X
X
X
Investigational product dispensing
X
X
X
X
X
X
X
X
Investigational product administration
X
→
→
→
→
→
→
→
X
Investigational product accountability
X
X
X
X
X
X
X
X
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Final Protocol Amendment 4, 06 June 2018
Page 39
Protocol Activity 
Single-Blind Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
11
12
13
14
15
16
17
18
19
Week
W28bb
W30
W32
W34
W36
W40
W44
W48
W52
Visit Window
±3 Days 
based on 
Day 1 visit
±3 Days based on W28 visit
Clinical assessments
IGA
X
X
X
X
X
X
X
X
X
SALT
X
X
X
X
X
X
X
X
X
X
Photographt
X
X
X
X
X
X
X
Patient reported outcome
Other
Prior and current concomitant 
Treatment(s)
→
→
→
→
→
→
→
→
→
Serious and non-serious adverse event 
monitoring
→
→
→
→
→
→
→
→
→
Contraception check
X
X
X
X
X
X
X
X
X
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Final Protocol Amendment 4, 06 June 2018
Page 40
Protocol Activity 
Single-Blind Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
20
21
22
23
24
25
26
27
28
Week
AT D1cc
AT W2
AT W4
AT W6
AT W8
AT W12
AT W16
AT W20
AT W24/AT EOT
Visit Window
±3 Days based on AT D1 visit
Medical procedures
Complete physical 
examinationd
X
X
Targeted physical 
examinatione
X
X
X
X
X
X
X
Vital signsf
X
X
X
X
X
X
X
X
X
12-Lead ECGg
X
X
Weighth
Audiogramj
X
X
Laboratory
Hematology
X
X
X
X
X
X
X
X
X
Blood chemistry
X
X
X
X
X
X
X
X
X
Fasting lipid Panelk
X
X
X
Cystatin C (and eGFR)l
X
X
X
X
X
X
X
X
X
Urinalysism
X
X
X
X
X
X
X
X
X
Urine pregnancy test
(WOCBP)o
X
X
X
X
X
X
X
X
X
Viral Surveillance: EBV, 
CMV, HSV1, HSV2, and 
VZV
X
X
X
X
X
 
 
 
 
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Final Protocol Amendment 4, 06 June 2018
Page 41
Protocol Activity 
Single-Blind Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
20
21
22
23
24
25
26
27
28
Week
AT D1cc
AT W2
AT W4
AT W6
AT W8
AT W12
AT W16
AT W20
AT W24/AT EOT
Trial treatment
Provide and review dosing 
instruction
X
X
X
X
X
X
X
X
Investigational product 
dispensing
X
X
X
X
X
X
X
X
Investigational product
administration
X
→
→
→
→
→
→
→
X
Investigational product
accountability
X
X
X
X
X
X
X
X
Clinical assessments
IGA
X
X
X
X
X
X
X
X
X
SALT
X
X
X
X
X
X
X
X
X
 
 
Other
Prior and current 
concomitant Treatment(s)
→
→
→
→
→
→
→
→
→
Serious and non-serious 
adverse event monitoring
→
→
→
→
→
→
→
→
→
Contraception check
X
X
X
X
X
X
X
X
X
Lesional biopsy for cellular 
and molecular analysesy
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Final Protocol Amendment 4, 06 June 2018
Page 42
For subjects in the Cross-Over Open Label Extension Period
Protocol Activity 
Drug 
Holiday#2
Cross-Over Open Label Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
29
30
31
32
33
34
35
36
37
Week
COD1
COW2
COW4
COW6
COW8
COW12
COW16 
COW20 COW24/COEOT
Visit Window
4 weeks
±3 Days based on COD1 visit
Inclusion/Exclusion criteria
Xgg
Medical procedures
Complete physical 
examinationd
X
X
Targeted physical 
examinatione
X
X
X
X
X
X
X
Vital signsf
X
X
X
X
X
X
X
X
X
12-Lead ECGg
X
X
Audiogramj
X
X
Laboratory
Hematology
X
X
X
X
X
X
X
X
X
Blood chemistry
X
X
X
X
X
X
X
X
X
Fasting lipid Panelk
X
X
X
Cystatin C (and eGFR)l
X
X
X
X
X
X
X
X
X
Urinalysism
X
X
X
X
X
X
X
X
X
Urine pregnancy test
(WOCBP)o
X
X
X
X
X
X
X
X
X
Laboratory 
Pharmacodynamics
FACS-TBNK 
X
X
X
X
 
Trial treatment
Provide and review dosing 
instructions
X
X
X
X
X
X
X
X
Investigational product 
dispensing
X
X
X
X
X
X
X
X
Investigational product
administration
X
→
→
→
→
→
→
→
X
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Final Protocol Amendment 4, 06 June 2018
Page 43
Protocol Activity 
Drug 
Holiday#2
Cross-Over Open Label Extension Period
Induction Phase
Maintenance Phase
Visit Identifier
29
30
31
32
33
34
35
36
37
Week
COD1
COW2
COW4
COW6
COW8
COW12
COW16 
COW20 COW24/COEOT
Visit Window
4 weeks
±3 Days based on COD1 visit
Investigational product
accountability
X
X
X
X
X
X
X
X
Clinical assessments
IGA
X
X
X
X
X
X
X
X
X
SALT
X
X
X
X
X
X
X
X
X
Photographt
X
X
X
X
X
X
X
Pharmacokinetic
Pre-dose PKv
X
X
X
X
Full PKw
X
X
 
 
Other
Prior and current concomitant 
Treatment(s)
→
→
→
→
→
→
→
→
→
Serious and non-serious 
adverse event monitoring
→
→
→
→
→
→
→
→
→
Contraception check
X
X
X
X
X
X
X
X
X
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Final Protocol Amendment 4, 06 June 2018
Page 44
Protocol Activity
Follow- up Period 
Early Termination Visitb
Visit Identifier
38
39
Week
FU1ee
EOSff
ET
Visit Window
Medical procedures
Complete physical examinationd
X
X
Targeted physical examinatione
X
Vital signsf
X
X
X
12-Lead ECGg
X
Weighth
X
Audiogramj
X
Laboratory
Hematology
X
X
X
Blood chemistry
X
X
X
Fasting lipid Panelk
X
X
Cystatin C (and eGFR)l
X
X
X
Urinalysism
X
X
X
Urine pregnancy test (WOCBP)o
X
X
X
Viral Surveillance: EBV, CMV, HSV1, HSV2, 
and VZV
X
Laboratory Pharmacodynamics
FACS-TBNK 
X
X
Trial treatment
Investigational product accountability
X
Clinical assessments
IGA
X
X
X
SALT
X
X
X
Photographt
X
X
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Page 45
Protocol Activity
Follow- up Period 
Early Termination Visitb
Visit Identifier
38
39
Week
FU1ee
EOSff
ET
Patient reported outcome
Pharmacokinetic
PKw
X
Other
Prior and current concomitant Treatment(s)
→
X
X
Serious and non-serious adverse event 
monitoring
→
X
X
Contraception check
X
X
X
Lesional biopsy for cellular and molecular 
analysesy
X
PKw
X
Abbreviations: →= ongoing/continuous event; AA = alopecia areata; 
; AT = Active Treatment; 
 CMV = Cytomegalovirus; CO = Cross-Over; EBV = Epstein-Barr virus; ECG = electrocardiogram; 
EOT = End of Treatment; EOS = End of Study; ET = Early Termination; FACS = fluorescence-activated cell sorting; FSH = follicle stimulating hormone; 
HBsAg = hepatitis B surface antigen;  HBcAb = hepatitis B core antibody; HCVAb = hepatitis C antibody; Hep B = Hepatitis B; HIV = human 
immunodeficiency virus; 
HSV1 = herpes simplex virus type 1; HSV 2 = herpes simplex virus type 2;
IG = Immunoglobulin; IGA = Investigator Global Assessment; IP10 = Interferon gamma-induced protein 10; 
 PHQ-8 = patient 
health questionnaire – 8 items; 
 SALT = Severity of Alopecia Tool; SBQ-R = Suicidal behaviors questionnaire –revised; 
TBNK = T, B, and NK cells; VZV = varicella zoster virus; WOCBP = women with childbearing potential; WONCBP = women of non-childbearing potential.
a.
Day relative to start of study treatment (Day 1).
b.
For subjects who discontinue early from the treatment period prior to Week 24 visit or subjects who discontinue early from the Single-Blind Extension
Period prior to Week 52 Visit or AT Week 24 visit or subjects who discontinue early from the Cross-Over Open Label Extension Period prior to Cross-Over 
Week 24 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.  Subject will then enter into the Follow-up Period with their first follow-up visit occurring 1 week after their last dose whenever possible.
c.
Medical history and AA disease history includes detailed histories of conditions specified in Study Procedures Section 7.3.2.
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d.
Complete physical examination consists 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. Dermatological examinations should include visual inspection of the breasts and external genitalia.
e.
Targeted physical examination consists of skin, heart, lungs, abdomen, and examination of body systems where there are symptom complaints by the 
subject.
f.
Vital signs should be performed before laboratory blood collection as specified in Section 7.3.1.
g.
ECG should be performed before laboratory blood collection.
h.
Height and weight will be measured without shoes.
i.
Chest X-ray or other appropriate diagnostic imaging (ie, CT or MRI) may be performed within 12 weeks prior to Day 1.  Official reading must be located in 
the source documentation.
j.
Audiogram testing may be performed within 8 weeks prior to Day 1. Audiogram for Screening must be completed for all subjects and results available prior 
to Day 1.  Audiogram testing at Week 12 must be completed and results available by the Week 16 Visit. Audiogram testing at Week 24 must be completed 
and results available by the Week 28 Visit. For subjects who are assigned to the placebo group and meet retreatment criteria, audiogram testing must be 
completed and results available by the AT D1 Visit unless an audiogram testing has been performed within 8 weeks prior to AT D1 Visit. For Cross-Over 
Open Label Extension Period, audiogram testing must be completed and results available by the CO D1 Visit unless an audiogram testing has been 
performed within 8 weeks prior to CO D1 Visit. For subjects that terminate early from the study, efforts must be made to complete the audiogram testing 
and obtain the results.
k.
Fasting lipid profile includes total cholesterol, triglycerides, HDL, and LDL.  A minimum of 8-hour fasting is required for fasting lipid profile evaluation.
l.
Serum cystatin C will be measured and cystatin C based eGFR will be calculated. 
m. Urinalysis will be performed by the central laboratory. Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, 
leukocyte esterase and/or protein.  Urine culture is performed if urinalysis is positive for nitrite and/or leukocyte esterase or if clinically indicated.
n.
Serum pregnancy testing at screening is required for female subjects of childbearing potential.  Follicle stimulating hormone (FSH) test to be performed at 
Screening to confirm postmenopausal status in female subjects who have been amenorrheic for at least 12 consecutive months.
o.
Urine pregnancy test must be performed prior to dosing with the investigational product for female subjects of childbearing potential. 
p.
Subjects who are positive for HIV will be screen-failed.
q.
Subjects who are HBsAg positive will be screen-failed.  Subjects who are HBsAg negative but HBcAb positive will be reflex-tested for HBsAb and, if 
HBsAb positive, may enroll; if HBsAb negative, they will be screen-failed.  Subjects who are positive for HCVAb will be screen-failed. 
r.
A documented TB Interferon Gamma Release Assay (IGRA) test performed within 12 weeks prior to Day 1 is acceptable.  Documentation of IGRA product 
used and the test result must be located in source documentation.  Subjects with a history of tuberculosis will be screen-failed as per protocol Section 7.3.6.
s.
Subjects should take the medication.  Subjects will be encouraged to take the medication after breakfast whenever possible.  However, at study visit days, 
subjects are to be instructed to refrain from dosing at home, and are to take the dose in the clinic.
t.
Photographs of treatment-eligible AA will be obtained at Screening to verify eligibility.  Scalp areas photographed should be recorded in study documents so 
that the same scalp region(s) will be photographed.  Photographs of 
 will also be taken. Additional photographs may also be taken at 
the investigator’s discretion.
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Page 47
 
v.
Blood sample for PK will be collected pre-dose at each visit as specified in SOA in Treatment Period and Cross-Over Open Label Extension Period. No PK 
samples are collected for Single-Blind Withdraw/Retreatment Extension Period.
w.
Blood samples for PK will also be collected at 0.5 hours post dose on Weeks 8 and 20; 0.5 and 1 hour on Week 12 during Treatment Period, and 0.5, 1, 2, 
and 4 hours post dose on Weeks 4 and 24 during Treatment Period and Cross-Over Open Label Extension Period. Blood sample for PK will be collected at 
early termination visit for subjects who discontinue early from the Treatment Period prior to Week 24 visit or during the Cross-Over Open Label Extension 
Period only if the most recent dose taken prior to ET visit was within 48 hours. No PK samples will be collected at ET visit for subjects who discontinue 
early from the Single-Blind Extension Period.
 
y.
Biopsy samples will be collected only on subjects who provide consent to participate in the biopsy sub-study at selected biopsy sites.  Biopsies of the 
lesional and non-lesional scalp (in subjects that have non-lesional scalp) will be obtained.  Biopsies of the lesional scalp at ET visit will only be obtained for 
subject who discontinue early from the Treatment Period prior to Week 24 visit. No biopsies will be obtained at ET visit for subjects who discontinue early 
from the Extension Periods.
z.
Biopsy at Week 4 is optional. 
aa. All subjects who complete the initial 24-week Treatment Period will be evaluated for potential entry into the Single-Blind Extension Period during the Drug 
Holiday #1. After the 4-week Drug Holiday #1, subjects will enter the Single-Blind Extension Period providing none of the Exclusion criteria #9, #10, and 
#26 are met and the audiogram result does not preclude patient’s entrance in the Single-Blind Extension Period. Subjects who meet Exclusion #9, #10, or 
#26 will be discontinued and enter the Follow-up Period.
bb. From Week 28, subjects who are assigned to active treatment group will receive the same respective active compound (PF-06651600 or PF-06700841), dose, 
and treatment duration as the original Treatment Period which consists of a 4-week induction period and a 20-week maintenance period, if any of the 
Exclusion criteria #9, #10, and #26 are not met and the audiogram result does not preclude patient’s entrance. From Week 28, subjects who are assigned to 
the placebo group will receive placebo for up to 24 weeks until they meet the retreatment criteria.
cc. For subjects who are assigned to the placebo group and meet the retreatment criteria, providing none of the Exclusion criteria #9, #10, and #26 are met and 
the audiogram result does not preclude patient’s entrance in the Extension Period (audiogram result available within 8 weeks is acceptable). 
dd. Urine myoglobin will be measured at Screening, Week 28, and in case of CK >3x ULN during the study.
ee. FU Visit 1 will occur 2 weeks after Cross-Over Week 24 Visit.  For early terminated subjects from the initial treatment period or the Single-Blind Extension 
Period or the Cross-Over Open Label Extension Period, FU Visit 1 will occur 1 week after their last dose whenever possible.
ff.
End of Study Visit will occur 2 weeks after FU Visit 1.
gg. All subjects who are assigned to receive active treatment (PF-06651600 or PF-06700841) directly and complete the segment for non-responder in 
Single-Blind Extension Period may be evaluated for potential entry into the Cross-Over Open Label Extension Period during the Drug Holiday #2.  Subjects 
will enter the Cross-Over Open Label Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Extension Period as well as the non-responder criteria is met. Audiogram result available within 8 weeks is acceptable. 
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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06651600 is an orally bioavailable small molecule that inhibits irreversibly JAK3 with 
selectivity over the other three JAK isoforms, JAK1, JAK2 and TYK2.  PF-06651600 also 
inhibits irreversibly the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase 
family (BTK, BMX, ITK, TEC, TXK), with high selectivity over the broader kinome.  
PF-06700841 is a dual inhibitor of human tyrosine-protein kinase 2 (TYK2) and Janus 
kinase 1 (JAK1).  Both compounds will be investigated in patients with alopecia areata (AA). 
1.2. Background and Rationale
1.2.1. Drug Development 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 critical for leukocyte activation, proliferation, survival and function. 
Cytokine receptors demonstrate restricted association with JAKs such that different receptors 
or receptor classes preferentially utilize a given JAK dimer combination to transduce their 
signal.  JAK1 pairs with JAK3 to mediate -common cytokine signaling and also with JAK2 
or TYK2 to transmit the signals of additional cytokines important in inflammation and 
immune responses including interleukin (IL) -2, -4, -5, -6, -12, -13, -15, -21, -23, -31, 
interferon gamma (IFN), and interferon alpha (IFN).  Following cytokine activation, 
receptor-associated JAKs are phosphorylated and in turn phosphorylate specific sites on the 
receptor intracellular domain.  Phosphorylation of specific sites on the intracellular domain 
of the receptor allows for the recruitment of signal transducers and activators of transcription 
(STATs) that can subsequently be phosphorylated by JAKs.16 Phosphorylated STAT 
molecules are released from the receptor, translocate to the nucleus where they bind to 
specific sites on the deoxyribonucleic acid (DNA) and regulate gene transcription.18
The tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family consists of 
five members including TEC, Bruton’s tyrosine kinase (BTK), bone marrow-expressed 
kinase (BMX), inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK/TXK), 
that are primarily expressed in hematopoietic cells.  TEC kinases play an important role in 
antigen receptor signaling and BTK and ITK regulate the signal transduction pathways 
initiated by the activation of B cell receptor (BCR) and T cell receptor (TCR), 
respectively.31,27
PF-06651600 is an orally bioavailable small molecule that inhibits irreversibly JAK3 with 
selectivity over the other three JAK isoforms, JAK1, JAK2 and TYK2. PF-06651600 also 
inhibits irreversibly the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase 
family (BTK, BMX, ITK, TEC, TXK), with high selectivity over the broader kinome.
PF-06651600 inhibits the cytotoxic function of CD8+ T cells and NK cells which have been 
implicated in the pathogenic process of AA.34,30 This inhibition may be mediated through 
mechanisms dependent on JAK3 and TEC kinase family members.33,28,29 PF-06651600 also 
potently inhibits signaling of the JAK3-dependent receptors for IL-15 and IL-21, which have 
been implicated in the pathogenic pathways of AA.32


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PF-06700841 is a dual TYK2/JAK1 inhibitor with a good selectivity profile over the other 
human kinases including JAK2.  TYK2/JAK1 are critical signaling kinases that regulate the 
signal transduction pathways triggered by several cytokines implicated in the pathogenesis of 
AA, including IFN, IL-2, IL-15, IL-12, and IL-23.4,25,6
1.2.2. Study Background
Alopecia areata is an autoimmune T-cell mediated disease characterized by non-scarring hair 
loss.5  The disease includes the following forms: limited patchy hair loss (patchy alopecia 
areata), complete loss of hair on the scalp (alopecia totalis) and complete loss of hair on the
scalp and the body (alopecia universalis).  Even though the patches are well-circumscribed, 
short fragile hairs are often seen in the periphery of lesions.  Nail changes are also seen in 
AA patients.  Pruritus is sometimes reported in AA patients although the affected skin 
usually does not have signs of inflammation.  Both males and females of all ages and races
can be affected.9  Alopecia areata is associated with immune diseases including asthma, 
allergic rhinitis, atopic dermatitis, thyroid disease, and automimmune diseases such as 
thyroiditis and vitiligo.9
The complex pathophysiology of AA is still not completely understood.  CD8+ T cells, 
natural killer (NK) cells, and mast cells are involved in the pathogenesis of alopecia areata.  
The possible cytokine pathways of the disease include a role for cytokines from type 1 helper
T cell (TH1) axis, including IL-1, IFN-and interferon -induced protein 10 (IP-10) that take 
part in the hair follicle cycle and immune-privilege collapse.  Mouse models have shown that 
IL-2 and IL-15 play a role in the initiation of auto-reactive CD8+ cells.  Recent studies have 
demonstrated AA signature with type 2 helper T cell (TH2), TH1, IL-23, and IL-9/TH9 
cytokine activation in scalp lesions of patients with AA.24
To date, there is no cure for AA.  Current treatment options are limited and include topical, 
intralesional, and systemic agents. Topical treatments usually have low efficacy and are not 
suitable for large areas or long-term use.  Intralesional steroids are also not applicable for 
large areas.  Healthcare providers have been using oral broad immunosuppressants including 
cyclosporine A, oral corticosteroids, mycophenolate mophetil, and azathioprine.  None of 
these immunosuppressive medications have been approved by the regulatory agency(ies) for 
treatment for AA.  The off-label use of immunosuppressive therapies is often associated with 
adverse events and side effect profiles that prevent their long-term use.4  Spontaneous hair 
growth is rare in moderate to severe AA patients.  The lack of effective treatments causes 
psychosocial distress with high prevalence rates of depression and anxiety in AA patients.1  
There is an unmet need for targeted therapy in patients with moderate to severe AA.
Recent studies have suggested potential utility of JAK inhibitors in the treatment of AA.  
Baricitinib, a JAK1/2 inhibitor, has reversed AA in a subject.11  Treatment with ruxolitinib, a 
JAK1/2 inhibitor, resulted in hair regrowth in a patient with AA and vitiligo.7  Tofacitinib, a 
pan JAK inhibitor, was reported to provide therapeutic effect in a patient with alopecia 
universalis.2


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1.2.3. Non-Clinical Pharmacokinetics and Metabolism 
1.2.3.1. 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 
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. 
Please refer to the Investigator’s Brochure (IB) for more details on the non-clinical 
pharmacokinetics and metabolism of PF-06651600.
1.2.3.2. 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. 


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Plasma protein binding of PF-06700841 was consistent across rat, monkey, and human with 
a fraction unbound (fu) of approximately 0.6-0.7.  Values of fu were lower in mouse 
(fu = 0.51) and rabbit (fu = 0.36).
Oxidative metabolites of PF-06700841 accounted for the primary routes of biotransformation 
in rat, monkey, and human consistent with CYP450 as the primary clearance route.  No 
unique human metabolites of PF-06700841 were evident compared to the safety species of 
rat and monkey. 
Clearance phenotyping of PF-06700841 indicated that CYP3A4 will be the predominant 
mediator of human metabolism with minor contributions from CYP1A2, 2C19, and 2D6. 
PF-06700841 showed a low risk of CYP450 inhibition and induction, 
UDP-glucuronosyltransferase (UGT) inhibition, OATP1B1/1B3 inhibition, and multi-drug 
resistance 1 (MDR1) inhibition.  PF-06700841 showed some potential to inhibit metformin 
mediated transport by organic cation transporter 2 (OCT2) (IC50=1.1 M), multidrug and 
toxin extrusion 1 (MATE1) (IC50=7.7 M) and MATE2K (IC50=17 M) in vitro.  The 
respective unbound Imax/IC50 ratios are 0.65, 0.09, and 0.04 for a predicted 60 mg clinical 
dose of PF-06700841 (unbound Cmax=0.72 M).  SimCYP modeling indicated a low risk of 
drug-drug interactions (DDI) perpetrated by a 60 mg once daily (QD) dose of PF-06700841 
(Cmax/AUC ratios 1.19/1.20). 
1.2.4. Safety Data
1.2.4.1. Non-Clinical Safety 
1.2.4.1.1. Non-Clinical Safety of PF-06651600
The nonclinical safety profile of PF-06651600 was characterized through the conduct of 
single- and repeat-dose studies of up to 6 months (rats) and 9 months (dogs) in duration, 
in vivo and in vitro safety pharmacology (neurofunctional, pulmonary, and cardiovascular), 
and in vivo and in vitro genetic toxicology studies.  Dose range-finding and definitive 
embryo-fetal development studies in rats and rabbits were also conducted.  In addition, an 
in vivo immunotoxicity study was done to characterize the risk for hypersensitivity, and 
phototoxicity was evaluated in rats.  The no observed adverse effect level (NOAEL) in the 
9-month toxicity study in dogs was 5 mg/kg/day, based on the finding of axonal dystrophy 
and associated auditory effects.  In the 9-month study in dogs, an adverse, 
PF-06651600-related dose-dependent finding of bilateral axonal dystrophy was observed 
within the olivary nuclei of the brainstem of male and female dogs administered 
20 mg/kg/day.  Auditory testing (Brainstem Auditory Evoked Potential [BAEP]) testing 
performed on recovery control and high dose animals showed severe to mild hearing loss and 
waveform defects, with partial recovery in the histological lesions and functional auditory 
effects indicated at the end of the 3-month recovery period.  The lowest observed adverse 
effect level (LOAEL) was 20 mg/kg/day.  The data from the 9-month dog study represent the 
limiting exposure.


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The current planned Phase 2 clinical study in AA include doses up to 200 mg QD (steady 
state unbound Cmax 1078 ng/mLand AUClast 3192 ng•h/mL).  Axonal dystrophy was not 
observed in the 8-week repeat dose dog study, and exposure at the NOAEL in the 8-week 
dog study was approximately 14x the predicted human exposure at the 4-week 200 mg 
clinical dose. 
The most commonly observed findings in the repeat-dose toxicity studies were effects on 
bone marrow and the immune and hematolymphopoietic systems that were consistent with 
the known pharmacological activity of JAK inhibitors.  Except at the high dose in the
9-month dog toxicity study, which was associated with signs indicative of infection, no 
adverse clinical signs, clinical pathology, or microscopic evidence of infection were observed 
in repeat dose toxicity studies, and effects related to the pharmacological activity of 
PF-06651600 were judged to be nonadverse. 
PF-06651600 was not mutagenic but was aneugenic in assays in vitro.  In vitro aneugenicity 
with kinase inhibitors is a common observation and is probably the consequence of off-target 
inhibition of kinases involved in cellular division.19  PF-06651600 did not induce 
micronuclei in vivo in rats at exposures 18x and 42x, respectively, the predicted human 
unbound Cmax and area under the plasma concentration time curve from time zero 
extrapolated to the last quantifiable concentration (AUClast) values at the highest dose of 
200 mg once daily (QD) in planned Phase 2 studies.
PF-06651600 is a covalent inhibitor of JAK3 and an integrated assessment of its potential to 
induce hypersensitivity and/or nonspecific toxicity reactions resulting from covalent 
interactions with other proteins was conducted.  The nonspecific reactivity potential of 
PF-06651600 was evaluated by assessing CYS containing kinase selectivity, human serum 
albumin binding, human hepatocyte recovery, and the modified mouse allergy model for 
hypersensitivity.  These assessments demonstrated a high level of specificity for the JAK3 
enzyme, minimal covalent binding to serum albumin, high recovery following human 
hepatocyte incubations (ie, minimal persistent binding to hepatocytes), and no evidence of 
hypersensitivity response in the modified mouse allergy model.
In an embryo-fetal development study in rats, the maternal NOAEL was 175 mg/kg/day.  
Skeletal malformations and variations, and lower fetal body weights occurred at 175 and 
325 mg/kg/day.  The exposure margins at the developmental NOAEL of 75 mg/kg/day were 
7.2x and 5.3x, respectively, the predicted steady state human unbound Cmax (1078 ng/mL)
and AUClast (3192 ng•h/mL) values at the highest daily dose of 200 mg in planned Phase 2 
studies.  In an embryo-fetal development study in rabbits, lower mean fetal body weights and 
higher incidences of visceral and skeletal malformations and skeletal variations were 
observed at 75 mg/kg/day.  The exposure margins at the developmental NOAEL of 
25 mg/kg/day in rabbits were 4.1x the predicted steady state human unbound Cmax 
(1078 ng/mL) and AUClast (3192 ng•h/mL) values at the highest daily dose of 200 mg in 
planned Phase 2 studies.  Please refer to Section 4.4.1 on the contraception requirements for 
participation in this study.


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There was no evidence of cutaneous or ocular phototoxicity following oral administration to 
rats for 3 days at doses up to 200 mg/kg/day.
In summary, the nonclinical safety profile of PF-06651600 has been adequately characterized 
to support progression into this Phase 2 study.  Adequate safety margins based on planned 
maximum doses and predicted exposures in patients were determined for effects observed in 
nonclinical studies.
Please refer to the IB for more details on the non-clinical information with PF-06651600.
1.2.4.1.2. Non-Clinical Safety of PF-06700841
PF-06700841 was evaluated in single-dose and repeat-dose toxicity studies up to 6 months 
(rats) and 9 months (monkeys) in duration.  Dose range-finding and pivotal embryo-fetal 
development studies (EFD) were conducted with PF-06700841 in rats and rabbits.  Target 
organs identified with PF-06700841 administration in rats and cynomolgus monkeys include 
the immune and hemolymphatic systems (thymus, spleen, lymph nodes, and bone marrow), 
gastrointestinal tract (body weight and weight gain effects), and adrenal gland (vacuolation).  
The findings in the thymus, spleen, lymph nodes, and bone marrow are consistent with the 
pharmacological activity of PF-06700841 and were not adverse because they were not 
associated with adverse clinical signs or adverse changes in hematology parameters, and
there was no evidence of test article-related infections in these animals. Gastrointestinal and 
adrenal effects were not adverse because they were either transient, of small magnitude 
and/or severity, and/or lacked associated tissue injury or inflammation, or changes in clinical 
pathology parameters.  In addition, there were inconsistent findings in the bone, liver, lung 
and prostate where the relationship to PF-06700841 is less clear.  Adverse findings in the 
central nervous system (decreased activity, mortality, prostration, convulsions) were 
observed at high exposures in pregnant rabbits, and emesis was observed in monkeys at high 
doses in studies 1 month in duration.  In safety pharmacology assessments 
PF-06700841-related effects were observed in the cardiovascular system (blood pressure, 
heart rate, QTc interval) and central nervous system (decreased locomotor activity).  Based 
on the lack of adverse findings at any dose, the NOAELs in the 6-month rat and 9-month 
monkey studies were 45 mg/kg/day in rats and 20 mg/kg in cynomolgus monkeys.  
Exposures at these doses were 6.2x to 40x the predicted efficacious human exposure 
(Cmax=218 ng/mL and AUC24=1730 ng•h/mL) from a 50 mg dose.
In the pivotal EFD study in rats, there were no PF-06700841-related maternal effects.  
However, higher incidences of fetal skeletal malformations (in long bones, scapulae, 
sternebrae or palatine bones) and variations (in the ribs, cervical vertebrae or sternebrae) 
occurred at 2 mg/kg/day, and delays in the ossification of the axial and appendicular 
skeleton occurred at 15 mg/kg/day.  In addition, lower embryo-fetal viability; lower mean 
fetal body weights, external malformations (cleft palate) and variations (whole body 
subcutaneous edema or edematous neck) occurred at 15 mg/kg/day.  The maternal NOAEL 
in rats was 15 mg/kg/day (13x and 11x the predicted efficacious human Cmax and AUC24
exposure from a 50 mg dose) and the developmental NOAEL was not determined but was 
<2 mg/kg/day, the lowest dose tested (2.2x and 1.3x the predicted efficacious human Cmax
and AUC24 exposure from a 50 mg dose).  In the pivotal EFD study in rabbits, there were no 


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PF-06700841-related maternal effects.  However, test article-related higher incidences of late 
resorptions and post-implantation loss occurred at 3 mg/kg/day and lower mean numbers of 
viable fetuses occurred at 7 mg/kg/day.  Test article-related skeletal variations were observed 
at 3 mg/kg/day, but were not adverse because most of these findings represent delays in 
ossification that would resolve with further growth and development.  The maternal NOAEL 
in rabbits was 7 mg/kg/day, the highest dose tested, (6.6x and 3.2x the predicted efficacious 
human Cmax and AUC24 exposure from a 50 mg dose) and the developmental NOAEL was 
1 mg/kg/day (0.8x and 0.4x the predicted efficacious human Cmax and AUC24 exposure from 
a 50 mg dose).  Please refer to Section 4.4.1 on the contraception requirements for 
participation in this study.
PF-06700841 was negative for mutagenicity in the bacterial reverse mutation assays.  
Although PF-06700841 was positive in the in vitro micronucleus assays in both CHO and 
TK6 cells, and was aneugenic in vitro (at 72,100 nM), it did not induce micronuclei, in vivo,
in reticulocytes in the 1-month study in rats (at exposures 35x to 51x the predicted human 
efficacious exposure (unbound Cmax=218 ng/mL and AUC24=1730 ng•h/mL) from a 
50 mg dose.
Although PF-06700841 absorbs in the ultraviolet A (UVA) and ultraviolet B (UVB) range,
PF-06700841 (100 mg/kg/day [unbound Cmax and AUC24 were 46x and 82x the predicted 
efficacious human exposure from a 50 mg dose]) had no evidence of phototoxicity in the skin 
or eyes of pigmented Long Evans rats in a 3-day phototoxicity study.  This demonstrates that 
PF-06700841 was not a phototoxicant, in vivo.
In summary, the nonclinical studies adequately support the planned clinical trials with 
PF-06700841.
Please refer to the IB for more details on the nonclinical information with PF-06700841.
1.2.4.2. Clinical Experience
1.2.4.2.1. Clinical Experience with PF-06651600
As of April 27, 2016, 74 subjects have received at least one active dose of oral PF-06651600.  
This accounts for 60 subjects from the first-in-human (FIH) B7981001 study who received 
active solution and 14 subjects from the bioavailability (BA) B7981003 study who received 
solution/tablet. 
The FIH study is a Phase 1, randomized, double blind, third party open, placebo controlled, 
single and multiple dose escalation, parallel group study in healthy adult subjects.  During the 
single dose period, subjects received doses of 5, 20, 50, 100, 200, 400, or 800 mg of 
PF-06651600 in a dose escalation format.  Subjects returned for the multiple dose periods to 
receive doses of 50, 200, or 400 mg QD or 100 or 200 mg twice a day (BID) for 14 days.


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1.2.4.2.1.1. Clinical Safety Experience with PF-06651600
Eighty (80) subjects were enrolled into the FIH study.  Single doses up to 800 mg and 
multiple doses up to 400 mg daily, as both 400 mg QD and 200 mg BID were administered.  
PF-06651600 appears to be generally safe and well-tolerated.  No clinically significant 
changes in vital signs, electrocardiogram or laboratory data were observed.  No dose limiting 
adverse events were reported and no subjects met the protocol prescribed individual stopping 
rules.  There were no deaths in the study. 
The most commonly reported all causality treatment emergent adverse events (TEAEs)
across both single ascending dose (SAD) and multiple ascending dose (MAD) PF-06651600 
cohorts were gastrointestinal (GI) disorders including diarrhea (9 subjects), abdominal pain 
(6 subjects), abdominal discomfort (2 subjects), and flatulence (3 subjects).  Change of bowel 
habit, constipation, fecal volume increased, discolored feces, nausea, paresthesia oral, and
vomiting have each also been reported (1 subject each event).  All cases were mild in 
severity with the exception of 1 moderate TEAE each of abdominal pain, dysphagia, and 
vomiting.
Skin and subcutaneous tissue disorders including, but not limited to rash, maculopapular 
rash, dermatitis acneiform, and erythema of mild to severe intensity were reported in the 
PF-06651600 cohorts and are summarized in Table 1 below.  There were no skin and 
subcutaneous tissue disorders reported in the 5, 20, 50, 200, 400, and 800 single dose 
cohorts; nor were there any skin and subcutaneous tissue disorders reported in the 50 mg QD 
multiple dose cohort.
Table 1.
Skin and Subcutaneous Tissue Disorder Occurrence
N= # of subjects
Adverse Event
SAD
50 mg
N=8
SAD 
100 mg
N=8
MAD 
100 mg 
BID
N=8
MAD 
200 mg 
QD
N=8
SAD
400 mg
N=16
MAD 
400 mg 
QD
N=24
MAD 
200 mg 
BID
N=8
A
P
A
P
A
P
A
P
A
P
A
P
A
P
Acne
0
0
0
0
0
0
0
0
0
0
2*
1*
0
0
Dermatitis 
acneiform
0
0
0
0
2*
0
0
0
0
0
0
0
1*
0
Dry Skin
0
1**
0
0
0
0
0
0
0
0
2*
1*
0
0
Eczema
0
0
0
0
0
0
0
0
0
0
0
1*
0
0
Erythema
0
0
0
0
1*
0
2*
1*
0 
1*
1*
0
1**
0
Rash
0
0
1*
0
0
0
0
0
0
0
1*
0
0
0
Rash macular
0
0
1*
0
0
0
0
0
0
0
3*
0
0
0
Rash 
maculopapular
0
0
1**
0
1**
0
0
0
0
0
0
0
2 
(1**/
1***)
0
Rash pruritic
0
0
0
0
0
0
0
0
0
0
0
0
1**
0
Seborrhoeic 
dermatitis
0
0
0
0
1*
0
0
0
0
0
0
0
0
0
Skin induration
0
0
0
0
0
0
0
0
0
0
0
0
0
1*
Abbreviations: A = active, P = placebo.
*- Mild **- Moderate ***- Severe


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Three (3) serious adverse events (SAEs) were reported in the FIH trial. 
The first event was a cutaneous abscess on the left buttock during the 200 mg single dose 
period in a subject who entered the study with a pre-existing boil on the left buttock.  This 
was assessed 19 days after the single dose was administered and was considered related to 
the study drug.  The subject was discontinued from treatment.  The SAE criterion was met as 
the incision and drainage procedure was performed in a hospital setting.
The second SAE was a sacrococcygeal cyst/pilonidal sinus abscess during the 400 mg single 
dose period.  This was assessed 19 days after the single dose was administered and was 
considered related to the study drug.  The SAE criterion was met as the incision and drainage 
procedure was performed in a hospital setting.
The third SAE was a varicella infection during the 400 mg QD MAD dose period.  The start 
date was 11 days after the last dose and was considered related to the study drug.  The source 
of the infection is unknown; however, a second subject, who had a reactivation of varicella 
zoster, may be the source as the subjects were confined during the same time.  The varicella 
infection resolved in 51 days. 
Please refer to the IB for more details on the clinical safety information with PF-06651600.
1.2.4.2.1.2. Clinical Pharmacokinetics Experience with PF-06651600
The PK parameters from the 5, 20, 50, 100, 200, 400 and 800 mg single dose levels are 
summarized below in Table 2.  In general, PF-06651600 area under the plasma 
concentration-time curve from time zero to infinity (AUCinf) increased in a dose related 
manner over the 5 to 800 mg dose range with a slightly greater than proportional increase 
observed over the 200 mg to 400 mg dose range.  Cmax increased with dose in an apparent 
dose proportional manner.
 
 
 
 
 
 
 
 
 
 
 
CCI


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PF-06651600 was absorbed rapidly following single doses of 5 mg to 200 mg with median 
time after administration of a drug when the maximum plasma concentration is reached
(Tmax) values ≤0.75 hours, and more slowly at the higher doses with a median Tmax of 1.0 and 
1.5 hours for the 400 mg and 800 mg doses, respectively.  Following attainment of Cmax, the 
disposition of PF-06651600 generally showed a monophasic decline at the lower doses of 
5 to 200 mg (mean t½ of 1.1 to 1.8 hours) while a biphasic decline observed at doses of 
400 to 800 mg (mean t½ of 2.2 to 2.5 hours).  An apparent trend toward longer t½ values at 
higher doses (400 and 800 mg) is probably due to concentrations remaining above the 
quantifiable limit for a longer period of time at the higher doses and defining a later terminal 
phase. 
The PK parameters following administration of 50, 200 and 400 QD and 100 mg and 
200 mg BID for 14 days are summarized below in Table 3.
On Day 14 of multiple-dose administration, PF-06651600 was absorbed rapidly with median 
Tmax values of 1 hour or less across the entire range of doses, from a total daily dose of 50 mg 
(50 mg QD) up to 400 mg (200 mg BID or 400 mg QD).  Following attainment of Cmax, the 
disposition of PF-06651600 was consistent with that observed following single-dose 
administration, showing a monophasic decline for the lowest doses and a biphasic decline 
following the 200 mg BID and 400 mg QD dosing regimens and a mean terminal t½ of about 
approximately 1.3 to 2.3 hours.  In general, plasma PF-06651600 AUCτ and Cmax increased 
with dose across the 50 mg to 400 mg total daily dose range in a dose related manner based 
on visual comparison of individual and dose normalized geometric mean Cmax and AUCτ
values.  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.
 
 
 
 
 
 
 
 
 
BID)
postdose at steady state; QD = Once daily; BID = Twice daily; Cmax = Peak plasma concentration;
CCI


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CL/F = apparent total body clearance; Vz/F = apparent volume of distribution; Aeτ% = Percent of dose 
recovered unchanged in urine over the dosing interval τ; CLr = Renal clearance.
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 Aeτ% of 4.1% to 7.0%).  
Renal clearance ranged from 42.9 mL/min to 63.1 mL/min.
 
 
  
 
 
1.2.4.2.1.3. Phase 2 Studies Safety Data
PF-06651600 is currently being investigated in patients with rheumatoid arthritis, alopecia 
areata, ulcerative colitis, and Crohn’s disease. 
Further details of the Phase 2 programs are provided in the IB.
1.2.4.2.2. Clinical Experience with PF-06700841
The B7931001 FIH study is the single clinical trial of PF-06700841 completed to date.  Of 
the 96 subjects randomized, 74 subjects have received at least one active dose of oral 
PF-06700841 in study B7931001.  This accounts for 41 healthy subjects who participated in 
the single and multiple ascending dose period of the trial who received active 
solution/suspension, 12 healthy subjects from the BA study who received suspension/tablet, 
and 21 subjects with chronic plaque psoriasis who were randomized to receive active 
solution/suspension over a 28 day treatment period. 
The FIH study was a Phase 1, randomized, double blind, third party open, placebo controlled, 
single and multiple dose escalation, parallel group study in healthy adult subjects and 
subjects with plaque psoriasis, with a relative bioavailability and food effect assessment of a 
tablet formulation of PF-06700841 in healthy adult subjects.  During the SAD period, 
41 healthy subjects received doses of 1, 3, 10, 30, 100, or 200 mg of PF-06700841 in a dose 
escalation format.  Twenty-one healthy subjects received doses of 10, 30, 100, or 175 mg QD 
for 10 days during the MAD period.  Subjects participating in the 100 mg multiple dose 
cohort returned for a third period to receive 50 mg PF-06700841 BID for 10 days.  Thirty 
subjects with moderate to severe chronic plaque psoriasis were also randomized into study 
B7931001, to receive once daily placebo (n=9), 30 mg (n=14), or 100 mg (n=7) 
PF-06700841 for 28 days, and underwent safety monitoring and clinical efficacy 
assessments.  An additional healthy volunteer cohort was included to support the evaluation 
of the relative 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 
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fasted, PF-06700841 solution/suspension fasted, and PF-06700841 tablet under fed 
conditions).
1.2.4.2.2.1. Clinical Safety Experience with PF-06700841
PF-06700841 was generally safe and well tolerated in the Phase 1 clinical study B7931001, 
which included both healthy subjects (n=66 randomized) and subjects with plaque psoriasis 
(n=30 randomized).  There were no deaths in the study, no serious adverse events, and no 
severe adverse events.  Subjects reported 11 TEAEs in the SAD phase, 22 TEAEs in the 
MAD phase, 39 TEAEs in the psoriasis phase, and 3 TEAEs in the BA phase.  All AEs were 
mild or moderate in severity.  Dose escalation stopping rules were not triggered at any dose 
level.
The most commonly reported all causality TEAEs across active subjects in both SAD and 
MAD cohorts were blood creatinine increased (reported in 2 subjects during the SAD period 
and 11 subjects during the MAD period), and neutropenia/neutrophil count decreased 
(reported in 4 subjects during the MAD period), which belong to the System Organ Class 
(SOC) categories of Investigations and Blood and Lymphatic System Disorders, respectively.
During the SAD/MAD, the AEs of blood creatinine increased were reported across dose 
levels from 10 mg up to 200 mg of PF-06700841, and occurred with greatest frequency in the 
175 mg QD and 50 mg BID MAD cohorts.  Neutropenia (Common Terminology Criteria for 
Adverse Events [CTCAE] Grade 3) occurred at the 175 mg QD and 50 mg BID dose levels 
during the MAD period.  All laboratory abnormalities reported as AEs were mild in severity, 
except for one case of neutropenia which was reported as moderate in severity (Grade 3 
neutropenia).  No neutrophil counts reached, or fell below 500 cells/mm3.
Other commonly reported all causality TEAEs during the SAD/MAD by SOC were Nervous 
System Disorders (2 events of headache and 1 event each of dizziness and presyncope during 
the SAD period, and 1 event each of headache, presyncope, and syncope reported during the 
MAD period), and Infections and Infestations (upper respiratory tract infection reported in 
2 subjects during the MAD period).  The AEs of upper respiratory tract infection were 
reported in 1 subject who received 10 mg PF-06700841 QD and 1 subject who received 
100 mg PF-06700841 QD.  These infections did not require antibiotic therapy (1 subject 
received symptomatic treatment), and did not require study treatment discontinuation. 
The most commonly reported all causality TEAEs across active subjects in the psoriasis 
cohorts treated with either 30 mg or 100 mg PF-06700841 were blood creatinine increased 
(reported in 7 subjects in the 30 mg dose group and 6 subjects in the 100 mg dose group), 
neutrophil count decreased ( reported in 1 subject in the 30 mg dose group and 1 subject in 
the 100 mg dose group), which belong in the SOC category of Investigations.
Other commonly reported AEs by SOC in the psoriasis cohorts included Nervous System 
Disorders (headache reported in 1 subject in the 30 mg dose group and 1 subject in the 
100 mg dose group, and paresthesia reported in 1 subject in the 100 mg dose group), 
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Infections and Infestations (1 report of upper respiratory tract infection and 1 report of herpes 
zoster infection, both in the 100 mg dose group). 
The AE of herpes zoster occurred in a single subject after completing 28-day treatment with 
PF-06700841 at the 100 mg QD dose level.  The subject had non-disseminated, herpetiform 
rash on the upper left back and left arm that was reported to have presented on Study Day 30 
(2 days after the last dose of PF-06700841).  The AE was mild in severity and was treated 
with acyclovir and Vicodin by the Investigator.
In the BA cohort, the SOCs with subjects reporting AEs were Gastrointestinal Disorders, 
Injury, Poisoning, and Procedural Complications, and Nervous System Disorders, each 
reported by 1 subject.  The reported AEs were nausea, contusion, and headache, each of 
which was experienced by 1 subject.  Subjects in the PF-06700841 100 mg oral 
solution/suspension fasted group reported treatment-related TEAE each of nausea and 
headache.  All TEAEs were mild in severity. 
Despite the AEs of blood creatinine increased observed in the healthy subjects (n=13 in the 
SAD/MAD cohorts) and psoriasis patients (n=13), the review of clinical laboratory 
parameters from study B7931001 confirmed there have been no noted clinically meaningful 
changes in the blood urea nitrogen, serum electrolytes, urinalysis, or cystatin-c based 
estimated glomerular filtration rate (eGFR) in subjects with elevated serum creatinine. 
Serum creatinine is primarily filtered by the kidney however; approximately 10-20% is 
actively secreted into the renal proximal tubules.  The active tubular secretion is mediated by 
transporters such as OCT2, organic anion transporter 2 (OAT2), and MATEs.  The proposed 
mechanism for the observed serum creatinine increases in study B7931001 is inhibition of 
creatinine transport (ie, transporter-mediated rather than direct nephrotoxicity), and is based 
on PF-06700841 potential to inhibit OCT2 creatinine transporter (IC50=1.1 μM; unbound 
Imax/IC50 ratio=0.25).  To differentiate from direct nephrotoxicity, the B7931001 protocol was 
amended (Protocol Amendment 2) to include collection of serum cystatin C.  Serum 
cystatin C was used to calculate eGFR in order to monitor for nephrotoxicity during the trial.  
Elevated serum creatinine in the absence of clinically meaningful changes in serum 
cystatin C based estimates of GFR during study B7931001 supports the transporter inhibition 
hypothesis.  Following the implementation of cystatin C-based kidney safety monitoring, no 
subjects were discontinued from treatment/study due to renal concerns.
Proof of mechanism was achieved in study B7931001.  
 
Please refer to the IB for more details on the clinical safety information with PF-06700841.
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1.2.4.2.2.2. Clinical Pharmacokinetics Experience with PF-06700841
Pharmacokinetic data from single doses of 1, 3, 10, 30, 100 and 200 mg and multiple doses 
of 10, 30, 100 and 175 mg QD and 50 mg BID mg administered for 10 days are summarized 
in Table 4 and Table 5, respectively.  Following single oral doses of 1 mg to 200 mg under 
fasted conditions, PF-06700841 was absorbed rapidly with median Tmax of 1 hour or less.  
Following the attainment of Cmax, concentrations appeared to decline in monophasic fashion.  
Mean terminal t½ ranged from 3.8 to 7.5 hours.  In general, both AUCinf and Cmax appeared
to increase proportionally with dose from 1 mg to 100 mg, and there appeared to be a trend 
toward more than proportional increases from 100 mg to 200 mg for AUCinf and Cmax.
 
 
 
 
 
 
 
 
 
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1.2.4.2.2.3. Phase 2 Studies Safety Data
PF-06700841 is currently being investigated in patients with psoriasis, alopecia areata, 
ulcerative colitis, and Crohn’s disease. 
Further details of the Phase 2 programs are provided in the IB.
1.2.5. Study Rationale
This multicenter, multiple-arm, placebo controlled study will be the first determination of 
safety and efficacy of PF-06651600 and PF-06700841 in subjects with AA. The objectives 
of this study are to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics for 
PF-06651600 and PF-06700841. In addition this study will provide opportunities for 
subjects to receive additional study treatment as there are no immunosuppressive medications 
approved for the treatment for alopecia areata. The current non-clinical toxicology packages 
support treatment duration ≥6 months for the maintenance doses. 
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The total sample size for the study is computed to be approximately 132 randomized.
The dose selection strategy was designed to balance pharmacology and safety.  A global PK 
model for each asset was developed using the data from the FIH studies for PF-06651600 
(Protocol B7981001) and PF-06700841 (Protocol B7931001), respectively.  Pharmacokinetic 
was assumed to be similar between healthy subjects and subjects with AA.  The activity of 
the JAK inhibitors was assessed by measurement of various PD markers and markers of
safety that were collected in the FIH studies and analyzed using indirect response modeling.  
The magnitude of change in these markers required for efficacy and/or safety is poorly 
understood.
By including two investigational drugs in a single study, the placebo group can be shared by 
both, resulting in fewer subjects being exposed to placebo and smaller overall study size.  
The inclusion of these two investigational drugs is appropriate as the target population for 
both is identical as are the efficacy outcome measures.  The current non-clinical toxicology 
packages for both PF-06651600 and PF-06700841 support the treatment duration.
By including a 4-week induction period and a 20-week maintenance period, this 24-week 
treatment study will determine the clinically relevant efficacy and safety of PF-06651600 and 
PF-06700841 in patients with moderate to severe AA.  The biopsy sub-study will establish
the effects of JAK3 and TYK2/JAK1 suppression on modulation of immune pathways
involved in AA. 
In the PF-06700841 FIH study B7931001, serum creatinine elevation was reported across 
dose levels in healthy volunteer and psoriasis patients (Section 1.2.4.2.2.1) but the review of 
clinical laboratory parameters confirmed there have been no noted clinically meaningful
changes in the blood urea nitrogen, serum electrolytes, urinalysis, or cystatin-c based eGFR 
in the subjects with elevated serum creatinine.  In order to monitor for any potential cases of 
decreased eGFR during this trial serum cystatin C will be collected to calculate eGFR in 
addition to serum creatinine. 
Currently there is no medications approved for treatment for AA.  The two Extension Periods
will provide an opportunity for subjects to receive additional active study treatment and 
active treatment with different MOA. 
This study includes a Single-Blind Extension Period to evaluate additional safety and 
tolerability of PF-06651600 and PF-06700841.  After the 4-week Drug Holiday #1, subjects 
who complete the initial 24 weeks of the protocol may enter the up to12 months Single-Blind 
Extension Period.  Subjects who discontinue prior to Week 24 will enter the Follow Up 
period and will not be eligible for the Single-Blind Extension Period. 
The study includes a Cross-Over Open Label Extension Period to evaluate the safety and 
tolerability of PF-06651600 and PF-06700841 for initial non-responders to either active 
treatment who will receive the opposite active treatment. Subjects who complete the 
segment for non-responders in Single-Blind Extension Period may be evaluated for potential 
entry into the Cross-Over Open Label Extension Period and receive opposite active 
treatment.  Subjects who discontinue prior to Week 52 will enter the Follow Up period and 


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will not be eligible for the Cross-Over Open Label Extension Period. Subjects who complete 
the Withdrawal/Retreatment segment for responder in Single-Blind Extension Period will go 
directly to the 4-week Follow-up Period. After the 4-week Drug Holiday #2, the 6-month 
Cross-Over Open Label Extension Period is followed by a 4-week Follow-up Period.
1.2.5.1. PF-06651600 Dose Rationale
The predicted total PK parameters for PF-06651600 based on simulations using the global 
PK model are provided in Table 6.
Table 6.
Summary of Predicted Steady State Plasma PF-06651600 Pharmacokinetic 
and Pharmacodynamic Parameters
Dose
mg QD
Total
Cmax
ng/mL
Predicted
Cmax
Marginsa
Total
AUCtau
ng·hr/mL
Predicted
AUC Marginsa
% Reduction from 
Baseline IP-10
Induction Treatment Period
200
1254 (2.1)
12
3712 (14)
14
42 (19)
Maintenance Treatment Period
50
259.5 (3.4)
5b
662.0 (20)
7b
18 (39)
AUCtau = Area under the concentration-time curve from zero to 24 hours postdose at steady 
state; Cmax = Peak plasma concentration; QD = Once daily; ( ) = Coefficent of variation 
expressed as a percent; human unbound fraction (fu) = 0.86; 1 ng/mL= 3.504 nM.
a.
Induction treatment period:  NOAEL-highest dose in dogs, 45 mg/kg/day; Week 8 mean male 
and female Cmax (free) = 12,000 ng/mL; Cmax (total) = 14,634 ng/mL; 
AUCtau (free) = 44,100 ng•h/mL; AUCtau (total) = 53,780 ng•h/mL.
b.
Maintenance treatment period: 9 month oral dog NOAEL-5 mg/kg; mean male and female 
Cmax(free) = 1115 ng/mL; Cmax (total) = 1297 ng/mL; AUCtau (free) = 4018 ng•h/mL; 
AUCtau (total) = 4672 ng•h/mL, dog (fu) = 0.82.
The induction dosing period (4 weeks) is supported by the nonclinical safety profile of 
PF-06651600 in dogs in a trial of 8 weeks duration.  The margins during the induction period 
are based on the NOEAL exposure from the highest dose (45 mg/kg).  The NOAEL in the 
9-month toxicity study in dogs was 5 mg/kg/day, based on the finding of axonal dystrophy 
and associated auditory effects.  The lowest observed adverse effect level (LOAEL) was 
20 mg/kg/day.  Thus, the data from the 9-month dog study represent the limiting exposure for 
chronic dosing. 
The predicted exposure during the induction treatment period at the top dose of 200 mg QD 
for 4 weeks is projected to maintain 12- and 14-fold safety margins for Cmax and AUCtau, 
respectively.  During the maintenance treatment period the 50 mg dose administered QD for 
20 weeks is projected to maintain safety margin for Cmax and AUCtau of 5- and 7-fold, 
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PF-06651600 inhibits signaling of the common-γ chain receptors for IL-15 and IL-21, which 
have been implicated in the pathogenic pathways of AA.  In lymphocytes, PF-06651600 
inhibited JAK1/JAK3-dependent STAT5 and STAT3 phosphorylation by IL-15 and IL-21 
respectively, with IC50s of 56.5 ng/mL and 103 ng/mL, respectively.  All other pathways 
were inhibited at IC50s >5708 ng/mL.  There is evidence of modulation of IP-10 a marker 
related to IFN-γ.
The predicted in vitro average percent inhibition of IL-15 and IL-21 signaling in human 
whole blood based on human PK for the selected dosing period is provided in Table 7.
Table 7.
Summary of the Predicted In Vitro Average Percent Signaling Inhibition 
Based on Steady State Pharmacokinetics of PF-06651600
Cytokine
Average Percent Signaling Inhibition
50 mg
200 mg
IL-15
44
81
IL-21
30
71
Pharmacological modulation of the target can be inferred from the predictions in Table 7.
1.2.5.2. PF-06700841 Dose Rationale
The predicted total PK parameters for PF-06700841 based on simulations using the global 
PK model are provided in Table 8.
 
 
 
 
 
 
 
 
 
 
 
The predicted exposure during the loading treatment period for PF-06700841 at the top dose 
of 60 mg QD for 4 weeks is projected to maintain 7.2- and 3.9-fold safety margins for Cmax
and AUCtau, respectively.  During the stable dosing treatment period the 30 mg dose 
administered QD for 20 weeks is projected to maintain safety margin for Cmax and AUCtau of 
15- and 9.3-fold, respectively.
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were measured in healthy 
subjects.  Based on indirect response modeling, the predicted percent reductions in the 
  Similarly, the predicted 
reduction of IP-10 levels was 47% and 51%, respectively for 30 and 60 mg QD.  The 
predicted maximum percent reduction in neutrophils and reticulocytes was 32% and 50%, 
respectively during the induction period and 30% and 36%, during the chronic dosing period. 
Subjects with moderate to severe psoriasis received doses of 30 mg or 100 mg QD or placebo 
for 28 days (B7931001).  Significant psoriasis disease modification as measured by placebo 
adjusted psoriasis area and severity index (PASI) change from baseline (mean change from 
baseline >-9 at 30 mg and mean change from baseline >-11 at 100 mg) was observed in the 
patients. 
Overall, the doses selected in this study are expected to demonstrate clinically relevant 
efficacy in subjects with AA.
1.2.6. Summary of Benefits and Risks
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.  The safety profile observed 
during the Phase 1 program for PF-06700841 appears to be acceptable at dosages up to 
175 mg administered orally. 
Additional information for these compounds may be found in the single reference safety 
document (SRSD), which for this study are the IBs of PF-06651600 and PF-06700841.
 
 
 
 
 
 
 
 
 
 
 
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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Study Objectives and Endpoints During Treatment Period
Primary Objective:
Primary Endpoint:
•
To evaluate the efficacy of PF-06651600 
and PF-06700841 compared to placebo at 
Week 24 in adult subjects with moderate to 
severe alopecia areata.
•
Change from baseline of Severity of Alopecia Tool 
(SALT) score at Week 24.
Secondary Objectives:
Secondary Endpoints:
Key Secondary Efficacy Objective: 
•
To evaluate the effect of PF-06651600 and 
PF-06700841 on SALT 30 at Week 24 in 
adult subjects with moderate to severe 
alopecia areata.
Key Secondary Efficacy Endpoint:
•
Proportion of subjects achieving a 30% improvement 
in SALT (SALT 30) at Week 24.
Other Secondary Efficacy Objectives:
•
To evaluate the effect of PF-06651600 and 
PF-06700841 on additional efficacy 
endpoints over time in adult subjects with 
moderate to severe alopecia areata in the 
Treatment Period.
Other Secondary Efficacy Endpoints:
•
Change from baseline in Investigator Global 
Assessment (IGA) at all time points up to Week 24 as 
specified in the Schedule of Activities (SoA).
•
Change from baseline in SALT at intermediate time 
points up to Week 24 as specified in the SoA.
•
Proportion of subjects achieving a 30% improvement 
in SALT (SALT 30) at intermediate time points up to 
Week 24 as specified in the SoA except for Week 24. 
•
Proportion of subjects achieving a 50%, 75% and 
100% improvement in SALT (SALT 50, SALT 75, 
and SALT 100) at all time points up to Week 24 as 
specified in the SoA.
•
Percentage change in SALT from baseline to Week 24 
at intermediate time points as specified in the SoA.
Safety Objectives:
•
To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time 
in adult subjects with moderate to severe 
alopecia areata in the Treatment Period.
Safety Endpoints:
•
Incidence of treatment-emergent adverse events (AEs)
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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•
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.2. Study Objectives and Endpoints during Single-Blind Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time 
in adult subjects with moderate to severe 
alopecia areata during the Single-Blind 
Extension Period.
•
Incidence of treatment-emergent adverse events (AEs)
during the Single-Blind Extension Period.
•
Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
profile, and liver function tests (LFTs) during the 
Single-Blind Extension Period.
 
 
 
 
•
Change from baseline in SALT during the 
Single-Blind Extension Period at all time points as 
specified in the SoA.
•
Proportion of subjects achieving SALT 30 during the 
Single-Blind Extension Period at all time points as 
specified in the SoA.
•
Proportion of subjects achieving SALT 50, SALT 75, 
SALT 100 during the Single-Blind Extension Period 
at all time points as specified in the SoA.
 
 
•
Time to achieve the retreatment criteria during the 
Withdrawal/Retreatment part of the Extension Period 
among subjects who achieved primary endpoint at 
Week 24.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.
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•
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.3. Study Objectives and Endpoints during Cross-Over Open Label Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over time 
in subjects who are non-responders to 
PF-06700841 and PF-06651600, 
respectively, during the Cross-Over Open 
Label Extension Period.
•
Incidence of treatment-emergent adverse events (AEs)
during the Cross-Over Open Label Extension Period.
•
Incidence of specific clinical laboratory abnormalities 
including but not limited to anemia, neutropenia, 
thrombocytopenia, lymphopenia, changes in lipid 
profile, and liver function tests (LFTs) during the 
Cross-Over Open Label Extension Period.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. STUDY DESIGN
Study Design Schematic
Placebo, n= 22*
Placebo, n=22*
PF-06651600, n =44
Screening
35 days
Induction
4 weeks
Maintenance 20 weeks
Biopsy Sub-study (selected sites)
Treatment Period only
PF-06700841, n= 44
60 mg
30 mg
200 mg
50 mg
* During the data analysis, the placebo groups will be combined in 
treatment period
Drug 
Holiday #1
4 weeks 
Placebo, n=22*
Treatment Period 
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Sponsor open, investigator open, subject blind.
# All subjects who complete the initial 24-week Treatment Period will be evaluated for potential entry into the Single-Blind Extension Period during the Drug Holiday #1.  Subjects will 
enter the Single-Blind Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s entrance in the 
Extension Period. Subjects will be assigned by the study designee(s) to receive either active treatment (PF-06651600 or PF-06700841) to start the segment for non-responder or 
placebo at Week 28 (after the 4-week Drug Holiday #1) to start the Withdrawal/Retreatment segment for responder. 
+ Subjects who are assigned to the placebo group will receive placebo for up to 24 weeks until they meet the retreatment criteria described in the SAP.  Subjects who meet the criteria 
will receive the same respective active compound (PF-06651600 or PF-06700841), dose, and treatment duration as the original treatment which consists of a 4-week induction period 
and a 20-week maintenance period, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation (audiogram 
result available within 8 weeks is acceptable).  Subjects who do not meet the retreatment criteria throughout the 24 weeks will go directly to the EOS visit. Subjects who complete 
the Withdrawl/Retreatment segment will go directly to the Follow-up Period and will not participate Cross-Over Open Label Extension Period.
* Retreatment criteria will be described in the SAP.  The study designee(s), who are independent of the study team, will inform the site if the subject meets the  criteria to start active 
treatment, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation (audiogram result available within 
8 weeks is acceptable). 
Single-Blind Extension Period
Cross 
Over 
Open 
Label
EOS
Drug 
Holiday 
#1
4 weeks# 
N
Do not meet retreatment criteria 
throughout 24 weeks
Placebo+
Meets 
Retreatmen
t Criteria *
Y
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
Withdrawal/Retreatment segment for responders
Segment for non-responders
FU 
Period
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤66
Induction
4 weeks
Maintenance 20 weeks


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Cross-Over Open Label Extension Period
PF-06651600
non responder
PF-06700841
non responder
Y
PF-06651600, n66
200 mg
50 mg
Induction
4 weeks
Maintenance 20 
weeks
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
Follow up 
4 weeks
N
* All subjects who are assigned to receive active treatment (PF-06651600 or PF-06700841) directly and complete the segment for 
non-responder in Single-Blind Extension Period may be evaluated for potential entry into the Cross-Over Open Label Extension 
Period during the Drug Holiday #2.  Subjects will enter the Cross-Over Open Label Extension Period providing none of the Exclusion 
criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s entrance in the Cross-Over Open Label 
Extension Period as well as the non-responder criteria is met at Week 52.  
Meet non-
responder 
criteria? *
Drug 
Holiday 
#2 
4 weeks*


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Study B7931005 will investigate the JAK3 inhibitor PF-06651600 and TYK2/JAK1 inhibitor 
PF-06700841 in AA.  This is a Phase 2a, randomized, double-blind, parallel group, 
multicenter study with two extension periods. The study will have a maximum duration of 
approximately 113 weeks. This includes an up-to-5 weeks Screening Period, a 24-week 
Treatment Period, a 4-week Drug Holiday (#1), an up to 12 month Single-Blind (investigator 
open, sponsor open and subject blind) Extension Period, a 4-week drug holiday (#2), a 
6-month Cross-Over Open Label Extension Period and a 4 week Follow-up Period. The 
study will enroll a total of approximately 132 subjects.  The study will be conducted at 
approximately 30 to 40 sites.
Subjects who have moderate to severe alopecia areata (≥50% hair loss of the scalp [SALT
score ≥50] without evidence of hair regrowth within the previous 6 months; current episode 
of fixed hair loss ≤7 years) present at the screening and baseline visits will be included in the 
study.  Photographs will be taken at the Screening Visit to verify eligibility (≥50% hair loss 
of the scalp).  Subjects will be randomized to PF-06651600 or matching placebo in a 
2:1 ratio or to PF-06700841 or matching placebo in a 2:1 ratio.  During the data analysis for 
the initial treatment period, placebo groups will be combined to yield final investigational 
product: placebo ratios of 1:1:1 for each investigational product.  Investigators, subjects, and 
the sponsor study team will be blinded as to treatment group.  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 in the interim CSR and published once the last subject 
last visit occurs for the initial 24-week Treatment Period. The interim study report may be 
shared with the PI when it is available. 
Subjects will be screened within 35 days prior to the first dose of study drug to confirm that 
they meet the subject selection criteria for the study.  The initial 24-week treatment consists
of a 4-week induction treatment period and a 20-week maintenance treatment period.
An induction dose of 200 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD
for 20 weeks of PF-06651600, an induction dose of 60 mg QD for 4 weeks followed by 
maintenance dosing of 30 mg QD for 20 weeks of PF-06700841, and matching placebo will 
be investigated. 
 
 
 
 
 
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Single-Blind Extension Period
Alopecia Areata is a disease with high unmet medical need. Currently there are no approved 
medications for treatment of AA.  An Extension Period has been added to this study to
evaluate additional safety and tolerability of PF-06651600 and PF-06700841. The Extension 
Period will become single-blind (investigator open, sponsor open and subject blind) upon 
approval of Amendment 4.
The Single-Blind Extension Period will provide an opportunity for subjects to receive 
additional active study treatment.  It will start after a 4-week Drug Holiday #1. The duration 
of the Single-Blind Extension Period can be up to 12 months.  Only subjects who complete 
Week 24 of the initial treatment period may be considered for eligibility to enter the 
Single-Blind Extension Period.  Subjects who discontinue during the initial treatment period 
will enter the 4-week Follow up Period and will not be eligible for the Single-Blind 
Extension Period. 
All subjects who complete the initial 24-week Treatment Period will be evaluated during the 
Drug Holiday #1 for potential entry into the Single-Blind Extension Period.  After the 
4-week Drug Holiday #1, subjects will enter the Single-Blind Extension Period providing 
none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Single-Blind Extension Period.  Subjects who meet 
Exclusion criteria #9, #10, or #26 will be discontinued and enter the Follow-up Period.
At Week 28 (after the 4-week Drug Holiday #1 that follows completion of Week 24), 
subjects will be assigned by the study designee(s) to receive either active treatment 
(PF-06651600 or PF-06700841) to start the segment for non-responder or placebo to start the 
Withdrawal/Retreatment segment for responder. The detailed criteria for treatment 
assignment will be described in the SAP. The study designee(s), who are independent of the 
study team, will provide the site with a treatment assignment when IP is being supplied via 
the IRT system post Week 24. A detailed communication plan will be provided to the site.  
The probability to receive active treatment in the Single-Blind Extension Period is 
approximately 33% to 100%. During the Single-Blind Extension Period, all the subjects 
assigned to placebo at Week 28 will have a probability of 100% to receive active treatment if 
they meet the retreatment criteria outlined in the SAP. 
During the Single-Blind Extension Period, subjects who are assigned to the active treatment 
(PF-06651600 or PF-06700841) at Week 28 will receive the same respective active 
compound (PF-06651600 or PF-06700841), dose, and treatment duration ( a 4-week 
Induction Period and a 20-week Maintenance Period) as the original Treatment Period to 
start the segment for non-responder. 
Subjects who are assigned to the placebo group at Week 28 to start the 
Withdrawal/Retreatment segment for responder will receive placebo for up to 24 weeks until 
they meet the retreatment criteria described in the SAP. These subjects will be assessed 
every 2 weeks during the first 8 weeks and then every 4 weeks up to 24 weeks by the study 
designee(s). The study designee(s), who are independent of the study team, will inform the 


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site if the subject meets the criteria to start active treatment. Subjects who meet the criteria 
will receive the same respective active compound (PF-06651600 or PF-06700841), dose, and 
treatment duration as the original treatment which consists of a 4-week induction period and 
a 20-week maintenance period, providing none of the Exclusion criteria #9, #10, and #26 are
met and the audiogram result does not preclude patient’s participation (audiogram result 
available within 8 weeks is acceptable).  Subjects who meet Exclusion criterion #9, #10, or 
#26 will be discontinued from the Single-Blind Extension Period and will go directly to the 
EOS visit.  Subjects who do not meet the retreatment criteria for initiation of active treatment 
throughout the 24 week period (Week 28 to Week 52) will go directly to the EOS visit.
Subjects who complete the Withdrawal/Retreatment segment will go directly to the 
Follow-up Period and will not participate Cross-Over Open Label Extension Period.
Any subject that has completed the initial 24 weeks of the Protocol B7931005 prior to 
Amendment 3 availability is eligible for evaluation for potential enrollment into the 
Single-Blind Extension Period. Subjects are to be discussed with the sponsor for possible 
enrollment for the Single-Blind Extension Period.
Cross-Over Open Label Extension Period
A 24 week Cross-Over Open Label Extension Period has been added to this study to evaluate 
safety and efficacy of PF-06651600 and PF-06700841 in subjects who complete the segment 
for non-responder in Single-Blind Extension Period and did not respond to the initial active 
treatment. More specifically, subjects who are PF-06651600 non-responder at Week 52 will 
receive PF-06700841 in the Cross-Over Open Label Extension Period. Subjects who are
PF-06700841 non-responder at Week 52 will receive PF-06651600 in the Cross-Over Open 
Label Extension Period. The subjects who were responders at Week 52 will enter the 
Follow-up Period directly. Non-responders are defined as subjects who have not achieved 
30% improvement in SALT relative to the baseline of the Treatment Period at Week 52. 
All subjects who complete the segment for non-responder in Single-Blind Extension Period 
and are non-responders at Week 52 will be evaluated during the Drug Holiday #2 for 
potential entry into the Cross-Over Open Label Extension Period.  After the 4-week Drug 
Holiday #2, subjects will enter the Cross-Over Open Label Extension Period providing none 
of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude 
patient’s entrance in the Cross-Over Open Label Extension Period as well as the 
non-responder criteria is met at Week 52. Audiogram result available within 8 weeks is 
acceptable. Subjects who meet Exclusion criteria #9, #10, or #26 will enter the Follow-up 
Period directly. Subjects who do not meet the non-responder criteria at Week 52 will be 
informed by the study designee(s) during the Drug Holiday #2 and go directly to the 4-week 
Follow-up Period. Subjects who discontinue during the Single-Blind Extension Period will 
enter the 4-week Follow-up Period and will not be eligible for the Cross-Over Open Label
Extension Period. 


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At Cross-Over Open Label Day 1 (after the 4-week Drug Holiday #2 that follows completion 
of Single-Blind Extension Period), non-responders will be assigned to receive either 
PF-06651600 or PF-06700841(the opposite of the assigned active treatment in the initial 
24 weeks and Single-Blind Extension Period). 
During the Cross-Over Open Label Extension Period, subjects will receive an induction dose 
of 200 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD for 20 weeks of 
PF-06651600 or an induction dose of 60 mg QD for 4 weeks followed by maintenance 
dosing of 30 mg QD for 20 weeks of PF-06700841. 
Any subjects who has completed the segment for non-responder in Single-Blind Extension 
Period prior to protocol Amendment 4 initiation at the investigator site is eligible for 
evaluation for potential enrollment into the Cross-Over Open Label Extension Period.  These 
subjects are to be discussed with the sponsor prior to any possible enrollment into the 
Cross-Over Open Label Extension Period.
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. 
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study. 
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study. 
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
3. Male or female subjects between 18-75 years of age, inclusive, at time of informed 
consent.
4. Male subjects able to father children and female subjects of childbearing potential and 
at risk for pregnancy must agree to use two highly effective method of contraception 
(per Section 4.4.1) throughout the study and for at least 28 days after the last dose of 
assigned treatment.


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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. 
5. Must meet the following alopecia areata criteria:
a.
Have a clinical diagnosis of moderate to severe alopecia areata (50% hair loss of 
the scalp [defined as SALT 50] without evidence of hair regrowth within 
6 months) at the screening and baseline visits;
b. Current episode of fixed hair loss 7 years.
6. If receiving concomitant medications for any reason other than AA, 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). 
7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun 
lamps or other ultraviolet light sources during the study.
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.


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3. Any psychiatric condition including recent or active suicidal ideation or behavior 
meets any of the following criteria: 
 
 
 
 
•
Any lifetime history of serious or recurrent suicidal behavior. 
•
Suicidal behaviors questionnaire –revised (SBQ-R) (Appendix 9) total score ≥8. 
•
Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) 
(Appendix 10) total score ≥15. 
•
The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 
•
In the opinion of the investigator or Pfizer (or designee) exclusion is required. 
4. Subjects considered in imminent need for surgery or with elective surgery scheduled 
to occur during the study. 
5. Subjects have other types of alopecia (including but not limited to traction, scarring 
alopecia).
6. Currently have active forms of other inflammatory skin disease(s) or evidence of skin 
conditions (eg, psoriasis, seborrheic dermatitis, lupus) at the time of the Screening or 
Day 1 Visit that in the opinion of the investigator would interfere with evaluation of 
AA or response to treatment.
7. Have received any of the following treatment regiments specified in the timeframes 
outlined below: 
Within 6 months of first dose of study drug:
•
Any cell-depleting agents including but not limited to rituximab: within 6 months 
of first dose of study drug, or 5 half-lives (if known), or until lymphocyte count 
returns to normal, whichever is longer.
Within 12 weeks of first dose of study drug:
•
Use of JAK inhibitors.
C
C
I


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
Other biologics: within 12 weeks of first dose of study drug or 5 half-lives (if 
known), whichever is longer.
Within 8 weeks of first dose of study drug:

Systemic treatments that could affect AA within 8 weeks of first dose of study 
drug 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 first dose of study drug or within 5 half-lives (if known), whichever is 
longer.

Intralesional steroid injection within 8 weeks of first dose of study drug or within 
5 half-lives (if known), whichever is longer.

Participation in other studies involving investigational drug(s) within 8 weeks of 
first dose of study drug or within 5 half-lives (if known), whichever is longer.
Note: Any investigational or experimental therapy taken or procedure performed 
for rheumatoid arthritis, psoriasis, vitiligo, thyroid disease, allergic rhinitis, or 
atopic dermatitis in the previous 1 year should be discussed with the Pfizer 
Medical Monitor (or designee).  Subjects cannot participate in studies of other 
investigational or experimental therapies or procedures at any time during their 
participation in this study.
Within 6 weeks of first dose of study drug:

Have been vaccinated with live or attenuated live vaccine.
Within 4 weeks of first dose of study drug:

Ultra-Violet B (UVB) phototherapy, Psoralen Ultra-Violet A therapy, or other 
phototherapy.
Within 2 weeks of first dose of study drug:

Topical treatments that could affect AA (eg, steroid cream; medicated shampoo;
or herbal hair care that could affect AA).
Within 1 week of first dose of study drug:

Herbal medications with unknown properties or known beneficial effects for AA.


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8. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and 
female subjects of childbearing potential who are unwilling or unable to use two 
highly effective 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. 
9. 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; or in the opinion of the investigator or Pfizer (or designee), the subject is 
inappropriate for entry into this study, or unwilling/unable to comply with STUDY 
PROCEDURES and Lifestyle Requirements.
10. Have current or recent history of clinically-significant severe, progressive, or 
uncontrolled hearing loss or auditory disease.
11. 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.
12. Have a history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster.
13. Have a history of systemic infection requiring hospitalization, parenteral 
antimicrobial therapy, or as otherwise judged clinically significant by the investigator 
within 6 months prior to Day 1 (for exception regarding Tuberculosis (TB) infection 
see Exclusion Criterion 24 or skin infections that lead to hospitalizations see 
Exclusion Criterion 14).
14. 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.
15. Have a history of alcohol or substance abuse within 6 months prior to Day 1 that in 
the opinion of the investigator or Pfizer (or designee) will preclude participation in 
the study.
16. A Screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant 
abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or 
brady-arrhythmias) or that are indicative of serious underlying heart disease 
(eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, 
Wolff-Parkinson–White syndrome).


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17. Have a known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
18. 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. 
19. 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.
20. Have undergone significant trauma or major surgery within 1 month of the first dose 
of study drug.
21. Require treatment with prohibited concomitant medication(s) (Section 5.8.2 and
Appendix 2) or have received a prohibited concomitant medication within 7 days or 
5 half-lives (whichever is longer) prior to Day 1.
22. History of human immunodeficiency virus (HIV) or positive HIV serology at 
screening. 
23. 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. 
24. 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 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 7.3.6 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.


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
Subjects with repeat indeterminate IGRA results may be enrolled after 
consultation with pulmonary or infectious disease specialist that determines 
low risk of infection (ie, subject would be acceptable for immunosuppressant 
treatment without additional action).

Subjects who test positive for QFT-G/ QFT-GIT test, but in the opinion of the 
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 with changes suggestive of active TB 
infection, unless previously performed and documented within 3 months prior to
Day 1.
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.
25. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
26. 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);

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 <80 ml/min/1.73m2
based on the age appropriate calculation;

enzymes aspartate transaminase (AST) or alanine transaminase (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;

CK >3 times the ULN and positive urine myoglobin;


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
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 will enroll a total of approximately 132 subjects (expected to provide 
approximately 90 completers).  Eligible subjects will be randomly assigned to a treatment 
group through the sponsor’s interactive response technology (IRT) system in the allocation 
ratio stratified by the disease subtype.
Eligible subjects will be randomized to PF-06651600 or matching placebo in a 2:1 ratio or 
PF-06700841 or matching placebo in a 2:1 ratio in the 24 week Treatment Period.  For 
analyses purposes, the two placebo arms will be combined during the treatment period.
A biopsy sub-study will be performed at selected sites.  Approximately 42 subjects will be 
randomized (expected to provide approximately 30 completers).  Subjects will be 
randomized to PF-06651600 or matching placebo in a 2:1 ratio or PF-06700841 or matching 
placebo in a 2:1 ratio.  During the data analysis for the biopsy sub-study, placebo groups will 
be combined to yield final investigational product: placebo ratios of 1:1:1 for each 
investigational product during the treatment period.
Eligible subjects will be stratified by the status of agreeing to participate in the biopsy 
sub-study and the disease sub-type.  Specifically there will be two strata for disease sub-type: 
AA (not totalis/universalis) and AA (totalis/universalis).  The study will be first stratified by 
the status of the biopsy sub-study and within each stratum for the status of the biopsy 
sub-study it will be further stratified by the disease sub-type. 
Subjects will be assigned to receive either active treatment (PF-06651600 or PF-06700841) 
or placebo at Week 28 (after the 4-week Drug Holiday #1 that follows completion of 
Week 24) by the study designee(s). The study designee(s), who are independent of study 
team, will provide the site with a treatment assignment when IP is being supplied via the IRT 
system post Week 24.
4.4. Lifestyle Requirements
In order to participate in the study, subjects must be aware of the following lifestyle 
guidelines and restrictions that apply during and after the study period. 

On study visit days that include fasting lipid panel, comply with fasting requirement 
for at least 8 hours prior to the visit. 

On study visit days, do not smoke or ingest caffeine during the 30 minutes prior to 
blood pressure and heart rate measurements. 

On study visit days, do not take the dose of study drug until instructed to do so by the 
investigator or designated study site staff.


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
During study, discontinue and avoid using certain medications and treatments 
(Section 4.2, Section 5.8.2, and Appendix 2). 

Agree to use appropriate contraception methods (Section 4.4.1).

Agree to avoid prolonged exposure to the sun and not to use tanning booths, sun 
lamps or other ultraviolet light sources during the study.

For subjects who undergo color application to their hair, it is recommended that the 
color application will be performed within one week prior to the scheduled study 
visits, if possible. This will facilitate the consistency of SALT 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.  PF-06700841 has been associated with 
demonstrated teratogenicity/fetotoxicity in animals.  Subjects who are, in the opinion of the 
investigator, sexually active and at risk for pregnancy with their partner(s) must agree to use 
2 methods of highly effective contraception throughout the study and for at least 28 days 
after the last dose of investigational product.  The investigator or his or her designee, in 
consultation with the subject, will confirm that the subject has selected 2 appropriate methods 
of contraception for the individual subject and his/her partner(s) from the list of permitted 
contraception methods (see below) and will confirm that the subject has been instructed in 
their consistent and correct use.  At time points indicated in the Schedule of Activities, the 
investigator or designee will inform the subject of the need to use 2 highly effective methods 
of contraception consistently and correctly and document the conversation, and the subject’s 
affirmation, in the subject’s chart.  In addition, the investigator or designee will instruct the 
subject to call immediately if 1 or both of the selected contraception methods is discontinued 
or if pregnancy is known or suspected in the subject or partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal), provided the subject 
or male subject’s female partner plans to remain on the same treatment throughout 
the entire study and has been using that hormonal contraceptive for an adequate 
period of time to ensure effectiveness. 
2. Correctly placed copper-containing intrauterine device (IUD).


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3. Male condom or female condom used WITH a separate spermicide product 
(ie, foam, gel, film, cream, or suppository).  For countries where spermicide is not 
available or condom plus spermicide is not accepted as highly effective 
contraception, this option is not appropriate.
4. Male sterilization with absence of sperm in the post vasectomy ejaculate. 
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive 
procedure (provided that occlusion has been confirmed in accordance with the 
device’s label).
All sexually active male subjects must agree to prevent potential transfer to and exposure of 
partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for at least 28 days after the last 
dose of investigational product.
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). 
For this study, the investigational product(s) are PF-06651600 and PF-06700841.


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5.1. Allocation to Treatment
Allocation of subjects to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number. The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject number, randomization number, and DU 
or container number assigned. The confirmation report must be stored in the site’s files. 
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 
5.2. Breaking the Blind
The study will be subject and investigator blinded.
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes should be 
broken only in exceptional circumstances when knowledge of the actual treatment code is 
absolutely essential for further management of the subject.  Investigators are encouraged to 
discuss with a member of the study team if they believe that unblinding is necessary.  When 
the blinding code is broken, the reason must be fully documented and entered on the case 
report form (CRF).
Details of unblinding plan for 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 research facility, it will be administered under the supervision 
of study personnel.
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 CRF and source document.  If compliance is <80%, 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.


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5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
Blinded PF-06651600 and PF-06700841 tablets and matching placebos 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.  They are equivalent to “PF-06651600” and 
“PF-06700841” with regard to this protocol.  The PF-06651600 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 and their matching placebos will be 
supplied in bottles and labeled according to local regulatory requirements.  Subjects will 
receive blinded labeled supplies throughout the study including the Extension Period.
Blinding occurs within investigational products, not across investigational products. The 
Extension Period will become single-blind (investigator open, sponsor open and subject 
blind) upon approval of Amendment 4. The Cross-Over Extension Period is 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 while PF-06700841 tablets and matching placebo 
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; Subjects should swallow the tablets with ambient 
temperature water to a total volume of approximately 240 mL; Subjects will swallow the 
investigational product whole, and will not 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.
If a dose is missed and the interval to the next dose is less than 8 hours, the missed dose 
should not be administered.


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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 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.
Site staff will instruct subjects on the proper storage requirements for take home 
investigational products. 


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5.7. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record. 
All study drug must be returned to the investigator by the subject at every visit and at the end 
of the trial.
5.7.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
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 study drug) will be documented as prior medications.  Medications 
taken after the first dose of study drug 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. 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.


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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 prior to study visits throughout the study, unless 
otherwise noted below.
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. 
5.8.2. Prohibited Medications and Treatments
Subjects will abstain from all concomitant medications as described in the Inclusion and 
Exclusion sections of the protocol and Appendix 2 Prohibited Concomitant Medications. 
Subjects should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications. 
A subject who is receiving simvastatin as concomitant medication should be switched at 
least 7 days prior to baseline to an alternative statin. Treatment with 
simvastatin-containing products should not be initiated during participation in this study. 
All medications and treatments that could affect AA 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 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 AA 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 5.8.3. 


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5.8.3. Vaccinations
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to the first dose of study drug, during the study, and for 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.
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. 
Subjects are required to fast for at least 8 hours prior to all visits that include fasting lipid
profile panel testing.  During the fasting period, subjects should refrain from all food and 
liquids (water and non-study medications are permitted). 
Due to possible need for PPD testing and chest radiograph, screening procedures may be 
performed over more than 1 visit within the 35 days prior to the Day 1 visit.
Visits should occur in the morning and prior to the subject’s dose.  To assure consistency and 
reduce variability, all study visits should occur in the morning whenever possible.  On days 
of study visits, subjects will receive their dose at the clinic during their study visit.
Urine pregnancy test must be performed prior to dosing with the investigational product for 
female subjects of childbearing potential through end of study (EOS).
The patient report outcome assessments should be completed before the other evaluations or 
treatments at the clinical visits whenever it is possible. 
Refer to Appendix 6 for guidelines on subject safety monitoring and discontinuation. 
6.1. Screening
Subjects will have up to 35 days of a screening period confirm that they meet the subject 
selection criteria for the study.  The investigator (or an appropriate delegate at the 
investigator site) will obtain informed consent from each subject in accordance with the 
procedures described in the Schedule of Activities section.
If the Mantoux PPD tuberculin skin test is given, the subject must return between 
48-72 hours post-injection for induration evaluation.


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Screening laboratory tests with abnormal results may be repeated once to confirm abnormal 
results (with the same screening number); the last value will be used to determine eligibility.  
If results return to normal within the 5-week screening period, the subject may enter the 
study. 
Sites will be permitted to re-screen subjects (with a new screening number) who initially do 
not meet eligibility criteria once.
The following procedures will be completed:

Obtain written informed consent.

Review Inclusion and Exclusion criteria.

Register subject in Impala.

Demography. 

Complete AA disease history includes collection of details of AA at Screening: AA 
background, AA history, AA diagnosis, pattern of scalp hair loss, body hair loss, nail 
involvement, the use of topical treatments, systemic treatments and other treatments 
for AA. 

Complete medical history, in addition to AA history, including history of drug, 
alcohol, tobacco use, skin rash, skin infection, and any dermal abnormalities that may 
predispose to infection will be collected at Screening.  Smoking status and average 
weekly alcohol consumption (units/week) will also be collected.

Obtain complete medication history of all prescription or nonprescription drugs, and 
dietary and herbal supplements taken within 35 days prior to the Screening Visit. 

In addition, previous drug treatments for AA taken within the 2 years before the 
Screening visit must be documented including the use of topical treatments,
intralesional treatments, systemic treatments and any other treatments. 

Conduct complete physical examination including dermatological full body 
examination.

Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.

Audiogram.

Perform single 12-lead electrocardiogram (ECG).

Obtain weight.


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•
Obtain height.
•
Chest radiograph (if previous chest radiograph has not been performed within 
12 weeks of Day 1, may require a visit to a different location).
•
Obtain samples for laboratory testing: Blood chemistry, hematology, urinalysis, urine 
myoglobin, serum FSH (female subjects of non-child bearing potential) or serum 
pregnancy test (female subjects of childbearing potential), HIV, HBsAg, HBcAb, Hep 
B reflex testing if applicable, and HCVAb.
•
Mantoux Purified Protein Derivative (PPD) skin test or IGRA test (unless performed 
within 12 weeks of Day 1).  If Mantoux PPD tuberculin skin test is performed, the 
subject must return between 48-72 hours post-injection for evaluation of induration.
•
Photographs to verify eligibility.
•
Conduct clinical evaluations including SALT, 
 SBQ-R, and PHQ-8.
•
Agree to use proper contraception methods.
•
Assess for occurrence of Adverse Events: The reporting period starts with the signing 
of the informed consent. 
6.2. Study Period
6.2.1. Visit 2, Day 1
•
Review of Inclusion/Exclusion Criteria.
•
If subject meets all Inclusion/Exclusion criteria, officially randomize subject into the 
study.
•
Review any changes in the subject’s prior and concomitant treatment information.
•
Review any changes in the medical history (any AEs happened before the first dosing 
should be reflected on the medical history).
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain weight.
•
Conduct complete physical examination. 
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•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for other laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
Cytomegalovirus (CMV), herpes simplex virus type 1(HSV1), herpes simplex virus 
type 2 (HSV2), VZV, 
 
•
Photography.
.
•
Conduct clinical evaluations including IGA, SALT,
•
Perform single 12-lead ECG.
 
 
•
Obtain Prep B1 and B2 samples.
•
Confirm proper contraception is being used.
•
Prior to dosing, obtain samples for PK analysis.
•
Administer first dose of study drug to subject.
•
Provide and review dosing instruction.
•
Dispense study drug supply to the subject.
 
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?” 
6.2.2. Visit 3, Day 15/Week 2 (±2 days)
•
Conduct targeted physical examination.
C
C
C
C
CCI
C
C
C
C
I
C
C
I
CCI


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•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, EBV, CMV, HSV1, HSV2, VZV, and urine pregnancy test (female 
subjects of childbearing potential only). 
•
Obtain Prep B1 samples.
•
Conduct clinical evaluations including IGA, SALT,
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Prior to dosing, obtain samples for PK analysis.
•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.3. Visit 4, Day 29/Week 4 (±2 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), 
, EBV, CMV, HSV1, HSV2, VZV
 
•
Prior to dosing, obtain samples for PK analysis.
CCI
C
C
C
C
CCI
CCI


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•
Photography.
•
Obtain Prep B1 and B2 samples.
•
Conduct clinical evaluations including IGA, SALT,
 
•
Confirm proper contraception is being used.
•
Optional lesional biopsy (for subjects who consent to participate in biopsy sub-study 
only).
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Collect blood samples for PK at 0.5, 1, 2, and 4 hours post dose. 
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.4. Visit 5, Day 43/Week 6 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Prior to dosing, obtain samples for PK analysis.
•
Conduct clinical evaluations including IGA, SALT,
CCI
C
C
C
C
I
CCI


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•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Administer study drug to the subject (from the previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.5. Visit 6, Day 57/Week 8 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Prior to dosing, obtain samples for PK analysis.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT,
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
C
C
C
C
CCI
C
C
I


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•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Collect blood samples for PK at 0.5 hours post dose.
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.6. Visit 7, Day 85/Week 12 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis and urine pregnancy test (female subjects of childbearing potential only), 
 EBV, CMV, HSV1, HSV2, VZV, 
 
•
Obtain Prep B1 and B2 samples. 
•
Prior to dosing, obtain samples for PK analysis.
•
Audiogram.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT,
 
•
Lesional biopsy (for subjects who consent to participate in biopsy sub-study only).
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
CCI
CCI
C
C
I
C
C
CCI


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•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Collect blood samples for PK at 0.5 and 1 hour post dose. 
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.7. Visit 8, Day 113/Week 16 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Prior to dosing, obtain samples for PK analysis.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
CCI
C
C
I
C
C


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•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.8. Visit 9, Day 141/Week 20 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Prior to dosing, obtain samples for PK analysis.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT,
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Collect blood samples for PK at 0.5 hours post dose.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.2.9. Visit 10, Day 169/Week 24/End of Treatment (±3 days)
•
Conduct complete physical examination.
CCI
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•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Perform single 12-lead ECG.
•
Audiogram.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
CMV, HSV1, HSV2, VZV, 
 
•
Obtain Prep B1 and B2 samples. 
•
Prior to dosing, obtain samples for PK analysis.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
•
Lesional biopsy (for subjects who consent to participate in biopsy sub-study only).
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study drug to the subject (from the previous container).
•
Collect blood samples for PK at 0.5, 1, 2, and 4 hours post dose. 
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
CCI
C
C
C
C
C
C
CCI


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6.2.10. Early Termination Visit 
For subjects who discontinue early from the treatment period prior to Week 24 visit or 
subjects who discontinue early from the Single-Blind Extension Period or Cross-Over Open 
Label Extension Period, the procedures scheduled for early termination (ET) Visit will be 
performed on the last day the subject takes the investigational product or as soon as possible 
thereafter.  Subject will then enter into the Follow-up Period with their first follow-up visit 
occurring 1 week after their last dose whenever possible.
•
Conduct complete physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Perform single 12-lead ECG.
•
Audiogram.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
CMV, HSV1, HSV2, VZV, 
 
•
Obtain Prep B1 and B2 samples. 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
•
Lesional biopsy (for subjects who consent to participate in biopsy sub-study only).
Biopsies of the lesional scalp at ET visit will only be obtained for subject who 
discontinue early from the treatment period prior to Week 24 visit. No biopsies will 
be obtained at ET visit for subjects who discontinue early in the Extension periods.
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
CCI
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I
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Final Protocol Amendment 4, 06 June 2018
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
Collect blood sample for PK for subjects who discontinue early from the treatment 
period prior to Week 24 visit or during the Cross-Over Open Label Extension Period 
only if the most recent dose taken prior to ET visit was within 48 hours. No PK 
samples will be collected at ET visit for subjects who discontinue early in the 
Single-Blind Extension period.

Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.3. Drug Holiday #1
All subjects who complete the initial 24-week Treatment Period will be evaluated for
potential entry into the Single-Blind Extension Period during the 4-week Drug Holiday #1. 
Subjects will enter the Single-Blind Extension Period providing none of the Exclusion 
criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s 
participation. Subjects who meet Exclusion criteria #9, #10, or #26 will be discontinued and 
enter the Follow-up Period.
6.4. Extension Periods
6.4.1. Single-Blind Extension Period
Subjects will be assigned to receive either active treatment (PF-06651600 or PF-06700841) 
to start the segment for non-responder or placebo to start the Withdrawal/Retreatment
segment for responder at Week 28 (after the 4-week Drug Holiday #1) by study designee(s) 
who are independent of study team.  The probability to receive active treatment in the 
Single-Blind Extension Period is approximately 33% to 100%.  During the Single-Blind 
Extension Period, all the subjects assigned to placebo at Week 28 will have a probability of 
100% to receive active treatment if they meet the retreatment criteria outlined in the SAP. 
Subjects who are assigned to the active treatment group during Drug Holiday #1 will enter 
the Single-Blind Extension Period at Week 28 providing none of the Exclusion criteria #9, 
#10, and #26 are met and the audiogram result does not preclude patient’s participation 
(audiogram result available within 8 weeks is acceptable). Subjects who are assigned to the 
placebo group during Drug Holiday #1 will enter the Single-Blind Extension Period at 
Week 28 providing none of the Exclusion criteria #9, #10, and #26 are met and the 
audiogram result does not preclude patient’s participation (audiogram result available within 
8 weeks is acceptable). Subjects who are assigned to the placebo group and meet the 
retreatment criteria will receive active treatment between Week 28 to Week 52 depending on 
when they meet the retreatment criteria.
6.4.1.1. Visit 11, Week 28 (3 days)

Review any changes in the subject’s prior and concomitant treatment information.

Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.


PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 107
•
Conduct complete physical examination. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for other laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine myoglobin, urine pregnancy test (female subjects of childbearing 
potential only), EBV, Cytomegalovirus (CMV), herpes simplex virus type 1(HSV1), 
herpes simplex virus type 2 (HSV2), VZV,
 
 
 
•
Photography.
 
•
Conduct clinical evaluations including IGA, SALT, 
•
Perform single 12-lead ECG.
•
Obtain Prep B1 and B2 samples.
•
Confirm proper contraception is being used.
•
Administer study IP to subject.
•
Provide and review dosing instruction.
•
Dispense study drug supply to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?” 
6.4.1.2. Visit 12, Week 30 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, EBV, CMV, HSV1, HSV2, VZV, and urine pregnancy test (female 
subjects of childbearing potential only). 
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 108
•
Obtain Prep B1 samples.
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.3. Visit 13, Week 32 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), 
EBV, CMV, HSV1, HSV2, VZV
 
•
Photography.
•
Obtain Prep B1 and B2 samples.
•
Conduct clinical evaluations including IGA, SALT, 
 
CCI
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I
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 109
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.4. Visit 14, Week 34 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Administer study IP to subject (from the previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
CCI
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 110
6.4.1.5. Visit 15, Week 36 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography. 
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.6. Visit 16, Week 40 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
CCI
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 111
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis and urine pregnancy test (female subjects of childbearing potential only), 
 EBV, CMV, HSV1, HSV2, VZV,
 
•
Obtain Prep B1 and B2 samples. 
•
Audiogram.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.7. Visit 17, Week 44 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
CCI
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
Page 112
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.8. Visit 18, Week 48 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
CCI
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I
CCI
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 113
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.9. Visit 19, Week 52 (±3 days)
•
Conduct complete physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Perform single 12-lead ECG.
•
Audiogram. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
CMV, HSV1, HSV2, VZV, 
 
•
Obtain Prep B1 and B2 samples. 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
CCI
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I
CCI


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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 114
•
Administer study IP to subject (from the previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10. Active Treatment (AT) Period
Only for subjects who are assigned to the placebo group at Week 28 and meet the retreatment
criteria, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram 
result does not preclude patient’s entrance in the Single-Blind Extension Period (audiogram 
result available within 8 weeks is acceptable). 
6.4.1.10.1. Visit 20, AT Day 1
•
Review any changes in the subject’s prior and concomitant treatment information.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Conduct complete physical examination. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for other laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
Cytomegalovirus (CMV), herpes simplex virus type 1(HSV1), herpes simplex virus 
type 2 (HSV2), VZV,
 
•
Photography.
 
•
Conduct clinical evaluations including IGA, SALT, 
•
Perform single 12-lead ECG.
•
Obtain Prep B1 and B2 samples.
•
Confirm proper contraception is being used.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject.
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B7931005
Final Protocol Amendment 4, 06 June 2018
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•
Provide and review dosing instruction.
•
Dispense study drug supply to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?” 
6.4.1.10.2. Visit 21, AT Week 2 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, EBV, CMV, HSV1, HSV2, VZV, and urine pregnancy test (female
subjects of childbearing potential only). 
•
Obtain Prep B1 samples.
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.3. Visit 22, AT Week 4 (±3 days)
•
Conduct targeted physical examination.
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Final Protocol Amendment 4, 06 June 2018
Page 116
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), 
 EBV, CMV, HSV1, HSV2, VZV
 
•
Photography.
•
Obtain Prep B1 and B2 samples.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.4. Visit 23, AT Week 6 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
CCI
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 117
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.5. Visit 24, AT Week 8 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography. 
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
CCI
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CCI
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B7931005
Final Protocol Amendment 4, 06 June 2018
Page 118
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.6. Visit 25, AT Week 12 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis and urine pregnancy test (female subjects of childbearing potential only), 
 EBV, CMV, HSV1, HSV2, VZV,
 
•
Obtain Prep B1 and B2 samples. 
•
Audiogram.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
CCI
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C
C
C
C
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PF-06651600; PF-06700841
B7931005
Final Protocol Amendment 4, 06 June 2018
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•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.7. Visit 26, AT Week 16 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
CCI
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Final Protocol Amendment 4, 06 June 2018
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6.4.1.10.8. Visit 27, AT Week 20 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.1.10.9. Visit 28, AT Week 24/AT End of Treatment (±3 days)
Subjects who complete the Withdrawal/Retreatment segment for responder will go directly to 
the Follow-up Period and will not participate the Cross-Over Open Label Extension Period.
•
Conduct complete physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Perform single 12-lead ECG.
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Final Protocol Amendment 4, 06 June 2018
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•
Audiogram. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), EBV, 
CMV, HSV1, HSV2, VZV,
 
•
Obtain Prep B1 and B2 samples. 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer active treatment (PF-06651600 or PF-06700841) to subject (from the 
previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.2. Drug Holiday # 2
Subjects who complete the segment for non-responder in Single-Blind Extension Period will 
be evaluated during Drug Holiday #2 for potential entry into the Cross-Over Open Label
Extension Period.  After the 4-week Drug Holiday #2, subjects will enter the Cross-Over 
Open Label Extension Period providing none of the Exclusion criteria #9, #10, and #26 are 
met and the audiogram result does not preclude patient’s entrance in the Cross-Over Open 
Label Extension Period as well as the non-responder criteria is met at Week 52. Audiogram 
result available within 8 weeks is acceptable. Subjects who meet Exclusion criteria #9, #10, 
or #26 will enter the Follow-up Period directly. Subjects who do not meet non-responder 
criteria at Week 52 will enter the Follow-up Period directly. Subjects who discontinue 
during the Single-Blind Extension Period will enter the 4-week Follow-up Period and will 
not be eligible for the Cross-Over Open Label Extension Period. 
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Final Protocol Amendment 4, 06 June 2018
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6.4.3. Cross-Over Open Label Extension Period
6.4.3.1. Visit 29, Cross-Over Day 1 (COD1)
•
Review any changes in the subject’s prior and concomitant treatment information.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Conduct complete physical examination. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for other laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), 
 
•
Photography.
 
.
•
Conduct clinical evaluations including IGA, SALT, 
•
Perform single 12-lead ECG.
•
Obtain Prep B1 and B2 samples.
•
Confirm proper contraception is being used.
•
Prior to dosing, obtain samples for PK analysis.
•
Administer study IP to subject.
•
Provide and review dosing instruction.
•
Dispense study drug supply to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?” 
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Final Protocol Amendment 4, 06 June 2018
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6.4.3.2. Visit 30, Cross-Over Week 2 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.3.3. Visit 31, Cross-Over Week 4 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only), 
•
Photography.
•
Obtain Prep B1 and B2 samples.
•
Conduct clinical evaluations including IGA, SALT, 
CCI
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Final Protocol Amendment 4, 06 June 2018
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•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Prior to dosing, obtain samples for PK analysis.
•
Administer study IP to subject (from the previous container).
•
Collect blood samples for PK at 0.5, 1, 2, and 4 hours post dose. 
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.3.4. Visit 32, Cross-Over Week 6 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Conduct clinical evaluations including IGA, SALT, 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
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•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Administer study IP to subject (from the previous container).
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.3.5. Visit 33, Cross-Over Week 8 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography. 
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
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6.4.3.6. Visit 34, Cross-Over Week 12 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis and urine pregnancy test (female subjects of childbearing potential only), 
•
Obtain Prep B1 and B2 samples. 
•
Audiogram.
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Prior to dosing, obtain samples for PK analysis.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
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6.4.3.7. Visit 35, Cross-Over Week 16 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.3.8. Visit 36, Cross-Over Week 20 (±3 days)
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only). 
•
Photography.
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•
Conduct clinical evaluations including IGA, SALT, 
 
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Administer study IP to subject (from the previous container).
•
Provide and review dosing instruction.
•
Dispense study drug to the subject.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.4.3.9. Visit 37, Cross-Over Week 24/Cross-Over End of Treatment (±3 days)
•
Conduct complete physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Perform single 12-lead ECG.
•
Audiogram. 
•
Obtain fasting samples for fasting lipid panel.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only),  
•
Obtain Prep B1 and B2 samples. 
•
Photography.
•
Conduct clinical evaluations including IGA, SALT, NRS for 
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•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Perform drug accountability procedures.
•
Prior to dosing, obtain samples for PK analysis.
•
Administer study IP to subject (from the previous container).
•
Collect blood samples for PK at 0.5, 1, 2, and 4 hours post dose. 
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.5. Follow-up Period
6.5.1. Visit 38, Followup 1 
Follow up Visit 1 will occur 2 weeks after AT Week 24 or Cross-Over Week 24.  For early 
terminated subjects from the initial treatment period or the Single-Blind Extension Period or 
the Cross-Over Open Label Extension Period, FU Visit 1 will occur 1 week after their last 
dose whenever possible.
•
Conduct targeted physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, and urine pregnancy test (female subjects of childbearing potential only).
•
Conduct clinical evaluations including IGA, SALT, 
.
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
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•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
6.5.2. Visit 39, End of Study Visit 
End of Study Visit will occur 2 weeks after FU Visit 1. 
Subjects who are assigned to the placebo group in the Single-Blind Extension Period and do 
not meet the retreatment criteria throughout 24 weeks will go directly to the EOS visit 
1 week after their last visit whenever possible.
The following procedures will be completed:
•
Conduct complete physical examination.
•
Obtain vital signs including pulse rate, blood pressure, respiratory rate (after at least 
5 minutes of rest) and oral or tympanic temperature.
•
Obtain samples for laboratory testing: hematology, blood chemistry, cystatin C, 
urinalysis, urine pregnancy test (female subjects of childbearing potential only),  
•
Obtain fasting samples for fasting lipid panel.
•
Prep B1 and B2 samples. 
•
Obtain weight.
•
Conduct clinical evaluations including IGA, SALT, 
 
•
Photograph.
•
Confirm proper contraception is being used.
•
Review any changes in the subject’s concomitant treatments information.
•
Assess for occurrence of Adverse Events by spontaneous reporting of adverse events 
and by asking the subjects to respond to a non-leading question such as “How do you 
feel?”
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6.5.3. Follow-up Contact
Follow-up contact only applies to subjects who have the EOS Visit taking place less than 
28 days after the last dose. Follow-up contact will be completed at least 28 calendar days, 
and up to 35 calendar days after the last administration of the investigational product to 
capture any potential adverse events (see the Time Period for Collecting AE/SAE 
Information section) and to confirm appropriate contraception usage (see the Contraception
section).  Contact with the subject may be done via a phone call.
6.6. 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 Treatment Period or 
Extension Periods will enter into the Follow-up Period with their first follow-up visit 
occurring 1 week after their last dose whenever possible and continue 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.
See Appendix 6 for guidelines on subject safety monitoring and discontinuation.  The ET 
Visit only applies to subjects who are randomized, received at least one dose of study drug,
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 Periods will enter the Follow-up Period with their first follow-up visit occurring 
1 week after their last dose whenever possible and continue 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 


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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 
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 
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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 and within 5 days after the first day of the 
menstrual period (counting the first day of the menstrual period as Day 1) before the subject 
may receive the study treatment.  In the absence of regular menstrual bleeding, the study 
candidate should have used 2 forms of contraception for at least 1 month before the second 
pregnancy test.  Pregnancy tests will also be repeated at every visit and at the end of the 
study to confirm that the subject has not become pregnant during the study.  Pregnancy tests 
will also be done whenever 1 menstrual cycle is missed during the active treatment period 
and when potential pregnancy is otherwise suspected, and may be repeated if requested by 
institutional review boards (IRBs)/ethics committees (ECs) or if required by local 
regulations.  In the case of a positive confirmed pregnancy, the subject will be withdrawn 
from administration of investigational product but may remain in the study for follow up. 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
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7.3. Safety Assessments
Safety will be assessed by the spontaneous reporting of AEs, physical examinations and 
clinical laboratory results in all subjects who receive at least one dose of the investigational 
product.  Unscheduled safety assessments may be performed at any time during the study to 
assess any perceived safety concerns.  Investigators and Pfizer Clinicians (or designees) will 
review individual subject data throughout the conduct of the study to ensure subjects’ 
well-being.
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7.3.1. Vitals Signs
Vital signs (blood pressure, pulse, respiratory rates and temperature) will be measured after 5 
minutes of rest as indicated in the Schedule of Activities. 
Vital signs should be performed before laboratory blood collection. 
It is preferred that body temperature be collected using the tympanic or oral methods and that 
the same method be used consistently throughout the study. 
Blood pressure (BP) will be measured using a standard calibrated blood pressure measuring 
device.  A BP device that uses multiple cuff sizes based on the arm circumference is the 
required type of device.  The appropriate cuff size for the subject must be used to ensure 
accurate measurement.  The arm circumference at the midpoint of the length of the upper arm 
should be measured to determine the appropriate cuff size in accordance with the 
specifications of the BP measuring device.  The same properly sized and calibrated blood 
pressure cuff will be used to measure blood pressure each time. 
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 AA disease history includes collection of details of AA at Screening: background, 
AA history, AA diagnosis, pattern of scalp hair loss, body hair loss, nail involvement, the use 
of topical treatments, systemic treatments and other treatments for AA.  Medical history, in 
addition to AA history, including history of drug, alcohol, tobacco use, 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 Screening visit.  Weight (lbs or kg) will continue to be measured and recorded at various 
timepoints according to Schedules of Activities.
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 


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performed by the investigator, sub-investigator or a qualified health professional per local 
guidelines. Dermatological examinations should 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, and 
abdomen and examination of body systems where there are symptom complaints by the 
subject. 
Complete and Targeted physical examinations are performed at various time points, see 
Schedules of Activities.
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. Audiogram
All subjects will have an audiogram at times specified in the Schedule of Activities.  
Audiogram testing taken at Screening or within 8 weeks prior to Day 1 must have results 
available prior to Day 1. Audiogram testing at Week 12 must be completed and results 
available by the Week 16 Visit. Audiogram testing at Week 24 must be completed and 
results available by the Week 28 Visit.  For subjects who are assigned to the placebo group 
and meet the pre-spcified criteria during the Single-Blind Extension Period, audiogram 
testing must be completed and results available by the AT D1 Visit unless an audiogram 
testing has been performed within 8 weeks prior to AT D1 Visit. For Cross-Over Open 
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CO D1 Visit unless an audiogram testing has been performed within 8 weeks prior to CO D1 
Visit. For subjects that terminate early from the study, efforts must be made to complete the 
audiogram testing and obtain the results.
When possible, the subject should have the audiogram performed at the same evaluation 
center during the study. 
If there is a clinically-meaningful, treatment-related decline in hearing from baseline, the 
subject will be followed off treatment with appropriate testing at regular intervals, until 
hearing returns to baseline or is determined to be clinically stable.
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) may be requested to be forwarded to Pfizer (and/or designee) at any time during 
the study.
7.3.6. Tuberculosis Testing
7.3.6.1. 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).
Subjects who test positive for QFT-G/ QFT-GIT test, but in the opinion of the PI are at low 
risk of TB infection may be referred to pulmonary or infectious disease specialist for 
consultation and potential IGRA test repeated once.  Subjects will be eligible if the repeat test 
is negative before the randomization.
Refer to lab manual for any additional processing information and shipping instructions.


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7.3.6.2. 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.
7.3.7. Special Safety Assessment
7.3.7.1. Dermatological Events
All subjects will have a dermatological full body exam at Screening Visit.  Skin lesions will 
be evaluated as defined in the National Cancer Institute Common Toxicity Criteria for 
Adverse Events v 4.0) and managed as Appendix 4. 
7.3.7.1.1. 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.
7.3.7.1.2. 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 7.3.7.1.1. 
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 CMV, EBV, HSV1, HSV2, and VZV, if applicable.
 
  
 
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Investigators will complete a questionnaire 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 
PI.
An independent dermatologist contracted by Pfizer will review all relevant data and 
summarize the data at the end of the study.
7.3.7.2. 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.8
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.17,3  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.10
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. 
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.26
7.4. Clinical Laboratory Tests
7.4.1. Blood Volume
Total blood sampling volume planned for this study is approximately 1000 mL.  Further 
details regarding the collection, processing, storage, and shipping of the blood samples will 
be provided in the lab manual.


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7.4.2. 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.

Subjects must abstain from all food and drink (except water and non-study 
medications) for an 8-hour overnight fast prior to fasting lipid profile panel collection 
according to Schedule of Activities.  All other labs (including PK sample collections) 
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Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Reticulocyte count
Platelet count
WBC count with differential
Total neutrophils (%, Abs)
Eosinophils (%, Abs)
Monocytes (%, Abs)
Basophils (%, Abs)
Lymphocytes (%, Abs)
BUN and Creatinine
Cystatin Ch
Creatine Phosphokinase
Glucose 
Na+, K+, Cl- ,Ca++
Total CO2 (Bicarbonate)
AST, ALT
Total Indirect & Direct Bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Fasting lipid Profile Panel f:
Total cholesterol
LDL 
HDL
Triglycerides
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Microscopy and/or 
cultured
HIVa
HBsAga
HBcAba
HepB reflex (HbsABa), if 
applicable
HCVAba
Serum pregnancy test a, c
Urine pregnancy test c
FSHa, g
QFT-G or other IGRA, or 
PPDa,e
EBV, CMV, HSV1, HSV2, 
VZV
 
 
 
Skin swab for herpetiform 
rashi
Skin swab for potential 
drug-related rashj
a
At Screening only.
b
HepB reflex testing only if HBsAg negative but HBcAb positive at Screening. 
c
Pregnancy tests (serum/urine) for females of childbearing potential.  Serum pregnancy test must be 
performed at Screening.
d
Only if urine analysis is positive for blood, protein, nitrites, or leukocyte esterase.
e
PPD results should be read within 48 to 72 hours.
f
Fasting lipid Profile Panel requires at least an 8 hour fast. Lipid profile panel will be completed per SOA, 
and will include total cholesterol, LDL, HDL, and triglycerides. 
g
Females of non-child bearing potential.
h
Cystatin C will be measured and cystatin C based eGFR will be calculated.
i
In case of a herpetiform rash (eg, suspected herpes zoster and herpes simplex) Section 7.3.7.1.1.
j
In case of a potential drug-related rash as specified in Section 7.3.7.1.2.
K
At Screening, Week 28, and in case of CK >3x ULN.
Clinically significant abnormal findings should be recorded as AEs.  Abnormal test results 
determined to be caused from laboratory error should not be reported as AEs.  Clinically 
significant laboratory findings at the final assessment should be followed to resolution or 
until determined by the Investigator to be stabilized.  Repeat tests may be indicated to 
establish this.  Refer to Appendix 6 for laboratory discontinuation criteria.
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7.5. Efficacy Assessments
7.5.1. Severity of Alopecia Tool (SALT)
Severity of alopecia tool is a quantitative assessment of AA severity based on scalp hair loss.  
A visual aid showing the division of the scalp hair into four quadrants, back, top of scalp, and 
both sides, with each of the four quadrants given an accurate determination of the % of scalp 
surface area covered, representing 24%, 40%, 18%, and 18% of the total scalp surface area.  
Score parameters are detailed in Appendix 3.  For any male subject, the male pattern 
alopecia should be permitted to score SALT 0 at the end of trial. Male pattern alopecia 
scoring may be considered for final adjudication by alopecia areata expert(s).
Subject should have a SALT score 50% at Screening and Baseline to be eligible for the 
study. 
The retreatment criteria during the Single-Blind Extension Period will be specified in SAP. 
The photos may be reviewed by an independent consultant to confirm the SALT scores.
7.5.2. Investigator Global Assessment (IGA)
The clinical evaluator of AA will perform an assessment of the overall improvement of AA
and assign an IGA score and category as described in Table 9.  This takes into account extent 
and density of regrowth by the SALT scoring system. 
For determination IGA, the SALT score would be determined at baseline and each follow-up 
visit and the percentage change from baseline determined by the following: (SALTbaseline –
SALTfollow-up)/SALTbaseline X 100% = % change from baseline.
Example: 75% hair loss at baseline (SALT score 75%), 50% hair loss at follow-up (SALT
score 50%), the percent regrowth = (75%- 50%)/ 75% X 100% = 33% regrowth.
The IGA should be permitted to score 0 (no change or further loss) at baseline.
Table 9.
Investigator Global Assessment (IGA) Score
Score
Description
0
no change or further loss
1
1-24% regrowth
2
25-49% regrowth
3
50-74% regrowth
4
75-99% regrowth
5
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7.7. Patient Report Outcome (PRO)
 
 
 
 
 
 
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7.7.3. Patient Health Questionnaire – 8 items (PHQ-8)
Patient health questionnaire – 8 items (Appendix 10) is a patient-report questionnaire consists 
of 8 items to assess subject depression level. 
At Screening Visit, if PHQ-8 total score ≥15, the subject will not be included in the study. 
7.7.4. Suicidal Behaviors Questionnaire-Revised (SBQ-R)
Suicidal behaviors questionnaire- revised (Appendix 9) is a patient-report questionnaire 
consists of 4 items to assess suicidal ideation, suicide attempts, threat of suicidal behavior, 
and likelihood of suicidal behavior. 
At Screening Visit, if SBQ-R total score ≥8, the subject will not be included in the study. 
7.8. Photography of Alopecia Areata Treated with Study Drug
Photographs of treatment-eligible alopecia areata will be obtained (according to the 
separately provided Photography Instructions) at various time points as per Schedule of 
Activities. 
Photographs of treatment-eligible AA will be taken at Screening Visit to verify eligibility
(≥50% hair loss of the scalp).  Scalp areas photographed should be recorded in study 
documents so that the same scalp region(s) will be photographed at all time points as 
applicable.  Photographs of 
will also be taken. Additional 
photographs may also be taken at the investigator’s discretion. 
Photographic services may be provided through a central photography lab selected by the 
sponsor.  Detailed procedures to assure consistency will be provided separately in a central 
photography lab instruction manual.
The photos may be reviewed by an independent consultant to confirm the SALT scores.
 
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7.10.8. Shipment of Pharmacodynamic Samples
The shipment address and assay lab contact information will be provided to the investigator 
site prior to initiation of the study.
7.11. Skin Biopsies
Biopsy samples will be collected only at pre-selected biopsy sites and only on subjects who 
provide consent to participate in the biopsy sub-study. 
The lesion(s) selected for biopsy will be outlined using a black permanent marker on plastic 
transparency film.  An area will be marked on the transparency film for identification and 
biopsy.  The film will be identified with the study number and subject’s identification 
number and retained with subject’s clinic/site source documents.
Biopsies of the lesional and non-lesional scalp (in subjects that have non-lesional scalp) will 
be obtained at each time point as specified in the Schedule of Activities.  In case of early 
termination, a lesional biopsy will be obtained at the ET visit.  All skin biopsies will be 
approximately 5 mm in diameter.
Biopsy samples will be prepared for histopathology and immunohistochemistry and for RNA 
extraction as described in a separate study manual that will be provided to investigators.  
Skin biopsies will be sent to designated laboratories for analysis following a schedule to be 
determined.
The shipment address and laboratory contact information will be provided to the investigator 
prior to initiation of the study.  Details on the procedure for skin biopsy and sample 
preparation will be provided to investigators in a separate study manual.
 
 
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As skin biopsies may be associated with risk of bleeding or infection, subjects will be 
instructed to contact the investigator or other designated site staff if they experience bleeding, 
warmth, swelling, tenderness, or erythema at the biopsy site; an unscheduled visit may be 
required for clinical assessment.  If a wound infection occurs at the site of the biopsy, a 
bacterial culture will be performed as part of standard of care procedures.
7.12. Rater Qualifications 
Clinical evaluations of alopecia areata 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 AA clinical trials may be permitted to perform the clinical evaluations of alopecia 
areata 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.
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)
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All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
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 
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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 
status is determined.
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 
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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.
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:

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
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

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 
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
Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
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);

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
Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE.  For purposes of 
consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 


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serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

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 
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In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Potential Cases of Decreased eGFR 
In 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) (Section 1.2.4.2.2.1). 
All subjects will have serum creatinine based and serum cystatin-C based eGFR calculated at 
baseline 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)14 and serum cystatin C (2012 
CKD-EPI eGFR)10 will be determined at times specified in the Schedule of Activities.  If an 
individual subject demonstrates a CONCOMITANT serum creatinine based AND serum 
cystatin C based eGFR decline of 30% compared to the subject’s baseline eGFR, then 
the subject should not be further dosed and adequate, immediate, supportive measures 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 then subject should be sent to 
a local emergency room for assessment of renal function.  Results should be repeated as 


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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. 
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.
8.4.4. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.4.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
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If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
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 concomitant 
medications including an herbal supplement which carried a pregnancy warning. 


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8.4.4.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.4.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.5. Medication Errors 
Other exposures to the investigational product under study may occur in clinical trial settings,
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.5.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength. 
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
9. DATA ANALYSIS/STATISTICAL METHODS
This section outlines the key planned statistical summaries and analyses for the data collected 
in this study.  A comprehensive overall Statistical Analysis Plan (SAP) will be provided prior 
to the un-blinding of the trial.  The SAP may modify the plans outlined in the protocol; 
however, any major modifications of planned analyses will be reflected in a protocol 
amendment if it is modified before data un-blinding.  If, after the trial is un-blinded, changes 
are made to the SAP, then these deviations to the plan will be documented, along with an 
explanation as to why they occurred, in the Clinical Study Report (CSR).
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 in the interim CSR and published 
once the last subject last visit occurs for the initial 24-week Treatment Period. The interim 
study report may be shared with the PI when it is available. 
9.1. Sample Size Determination
The standard deviation of SALT mean change from baseline at Week 24 was calculated by 
simulating subject level data from the summary data from the open label study in AA using 
tofacitinib.12  The adjusted standard deviation (SD) for the change from baseline was 
calculated to be ~32.43. 
The sample size is based on the primary efficacy endpoint, mean change from baseline in 
SALT score at Week 24.  The null hypothesis to be tested for one compound (PF-06700841) 
is to assess if the difference between PF-06700841 and placebo is less than or equal to 20 vs 
the alternative hypothesis if the difference between PF-06700841 and placebo is greater than 
20.  Using a between-group comparison at Week 24, for PF-06700841 vs placebo and 
PF-06651600 vs placebo, 30 completers in each arm provides approximately 89.9% power to 
detect a true mean change from baseline in SALT total equal to 15.  This is for a test 
conducted at a one-sided level of significance of 2.5% (adjusted for two active vs placebo 
comparisons).  Assuming a 30% average drop-out in the study the total sample size would 
be ~132.
For the biopsy sub-study which will be performed at selected sites, approximately 42 subjects 
will be randomized (30 completers; assuming 30% drop out rate.  Subjects will be 
randomized to PF-06651600 or matching placebo in a 2:1 ratio or PF-06700841 or matching 
placebo in a 2:1 ratio.  During the data analysis for the biopsy sub-study, placebo groups will 
be combined to yield final investigational product: placebo ratios of 1:1:1 for each 
investigational product.  Due to the exploratory nature of the sub-study, there is no formal 
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There is no re-randomization at the start of the Single-Blind Extension Period or Cross-Over 
Open Label Extension Period. 
9.2. Efficacy Analysis During the Treatment Period
All subjects who receive at least one dose of randomized study medication, and have a 
baseline and at least one post-baseline measurement (after taking randomized study 
medication) will be included in the efficacy data analyses. Alpha adjustments for primary 
and secondary endpoints will be described in the SAP.
9.2.1. Analysis of the Primary Endpoint During the Treatment Period 
The primary efficacy endpoint is change from baseline in the SALT score.  The primary time 
point is Week 24.  Baseline is defined as the last measurement prior to randomization (Day 1 
of the Double-Blind Treatment Period). All other collection time points will be considered
secondary.  A linear mixed-effect repeated measures model with fixed effects for treatment, 
time (visit), baseline value of SALT and investigator site, and a random effect for subject, 
will be used to analyze the change from baseline in the SALT score (this will be denoted as 
the primary analysis).  This model may also include effects for treatment by time interaction 
and baseline value of SALT by treatment interaction and disease sub-type.  The estimation 
method used will be restricted maximum likelihood.  Due to the unknown nature of the 
longitudinal data, different covariance structures among repeated measures will be examined 
based on model diagnostics.  Using this model, adjusted 95% upper confidence bound 
comparing the mean change from baseline in SALT estimates at Week 24 for PF-06700841 
vs. placebo and PF-06651600 vs placebo will be computed. Alpha adjustments for primary 
and secondary endpoints will be described in the SAP.
Supplemental analyses of the primary variable will be performed to support the robustness of 
the conclusions drawn from the primary analysis described above such as, verify assumptions 
of possible normality violations, sensitivity analyses to account for informative drop-outs.  
Details of these supplemental analyses will be included in the SAP.
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be 
provided for the baseline and change from baseline values by treatment group and visit.
9.2.2. Analysis of Secondary Endpoints During the Treatment Period
The key secondary efficacy endpoint is proportion of subjects achieving a 30% improvement 
in SALT (SALT 30) at Week 24.  The primary time point is Week 24.  All other collection 
time points will be considered secondary. 
The frequency and percentage of SALT 30 responders will be presented at all
post-randomization visits as specified in the SoA where SALT is collected.  The SALT 30 
response rate will be analyzed by a generalized linear mixed model, with fixed factors of 
treatment, visit, treatment by visit, baseline SALT score.  Within-subject covariance structure 
may be considered by assessing various models (eg, unstructured, Toeplitz and first order 
autoregressive etc.) and the corresponding results will be compared for the sake of checking 


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robustness.  Comparison to placebo for this key secondary endpoint will be conducted at 
Week 24 as described by the statistical model above.
Detailed description of analyses for other secondary endpoints will be outlined in the SAP.  
Continuous and discrete modelling techniques will be applied whenever applicable. 
9.2.3. Analysis of Other Endpoints During the Treatment Period
 
 
 
Continuous and discrete modelling techniques will be applied whenever applicable.  
Distribution summaries will be presented by means of summary tables data visualization 
methods.  Detailed description of analyses for other endpoints will be outlined in the SAP.
 
9.2.3.1. Pharmacokinetic Analysis During the Treatment Period
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06651600 or PF-06700841 and in whom at least one concentration value is 
reported.
PK concentrations will be summarized and presented with summary statistics.  A population 
PK model may be developed for the purpose of estimating PK parameters.  Any population 
PK model developed to characterize the PK data will be reported separately.
Data permitting, the relationship between exposure and clinical responses (efficacy and 
safety) from subjects with AA may be explored using either observed or modeled exposures.  
Any population analyses conducted will not be part of the clinical study report (CSR) and 
may be reported separately.
9.2.3.2. PK/PD Unblinding Plan
A PK/PD unblinding plan approved by the clinical lead, clinical pharmacology lead and 
statistical lead may be in place to describe the procedures to be employed in safeguarding the 
study blind for members of the study team.  These procedures will be in accordance with 
applicable Pfizer standard operating procedures (SOPs) for releasing randomization codes 
and breaking the study blind.  Under this plan a group of statisticians, PK/PD data provider, 
PK/PD analyst and PK/PD support would be unblinded in order to initiate the building of 
statistical models of the PK, dose/response as well as exposure/response analysis models and 
conduct associated simulations.  The aim of this work would be to facilitate a fuller 
interpretation of the study upon completion (at appropriate interim milestone).  This group 
will not serve on the study team during the period of early unblinding.  The unblinding may 
occur after the last subject has been randomized.  The details of the procedures will be 
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described in the PK/PD Unblinding Plan for Modelling and Simulation for study B7931005 
which will be finalized prior to the start of the PK/PD unblinding. 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.3. Safety Analysis During the Treatment Period
The safety analysis set will include all subjects who have received at least one dose of the 
drug or placebo.  Safety data will be presented in tabular and/or graphical format and 
summarized descriptively, where appropriate.  All safety endpoints will be listed and 
summarized in accordance with Pfizer Data Standards.  Categorical outcomes (eg, AEs) will 
be summarized by subject counts and percentage.  Continuous outcome (eg, BP, heart rate, 
etc) will be summarized using N, mean, median, standard deviation, etc.  Change from 
baseline in laboratory data and vital signs will also be summarized. Categorical summaries 
will be produced for ECGs.  Subject listings will be produced for these safety endpoints 
accordingly.
The safety analyses will be carried out in the safety population, detailed analyses will be 
described in the SAP. 
 
 There will be no adjustment for multiple comparisons or 
stratification factor in the analyses unless specified.
 
 
Nominal p-values (Tier 1 events only) and 95% confidence intervals (Tier 1 and Tier 2 
events) will be provided for between treatment differences in the percentage of subjects with 
events.  Reporting p-values and confidence intervals will follow Pfizer standard practice in 
the 3-tier approach.
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9.4. Analysis During the Single-Blind Extension Period and Cross-Over Open Label
Extension Period
9.4.1. Exploratory Efficacy Analysis During the Single-Blind Extension Period
Descriptive statistics will be provided for the exploratory efficacy analysis. Binary endpoints 
will be summarized with frequency and percentage by time point, and the continuous 
variables will be summarized with n, mean, median, standard deviation, etc.  These 
summaries may be provided by the strata of responding status at entry to the Single-Blind 
Extension Period.
The efficacy will be compared between subjects who enter the Single-Blind Extension Period 
non-responder segment to receive active treatment directly and the subjects who are retreated 
with active treatment in the Single-Blind Extension Period Withawal/Retreatment segment. 
Additionally, for subjects who enter the Single-Blind Extension Period non-responder 
segment to receive active treatment directly and are initially treated with placebo in the 
Double-Blind Treatment Period, the active treatment will be compared with placebo in the 
Double-Blind Treatment Period to examine the efficacy. For continuous endpoints (such as 
SALT, 
 the change from baseline scores will be analyzed using an Mixed 
effect Model Repeat Measurement (MMRM) model as described for the Treatment Period 
primary efficacy analysis. The binary endpoints such as SALT30, SALT50, SALT75, 
SALT100,
 
respectively will be analyzed by generalized linear mixed model (GLMM) on 
observed data, and Chan and Zhang’s exact method applied to non-responder imputation 
(NRI) data. 
 Baseline is defined as the last measurement prior to 
randomization (Day 1 of the 24 week Double-Blind Treatment Period) when deriving the 
continuous and binary endpoints.
In addition, for subjects on placebo in the Single-Blind Extension Period, to estimate the 
maintenance of the efficacy effect, Kaplan-Meier method will be used to analyze the time to 
event (re-treatment) endpoint; and the change in SALT from Week 24 will be analyzed by 
MMRM model to explore the magnitude of efficacy over time after stopping active 
treatment.
All subjects who have received at least one dose of planned investigational product in the 
Single-Blind Extension Period will be included into the efficacy analyses. Detailed 
methodologies of these analyses will be described in the SAP.
 
 
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9.4.4. Safety Analysis for Single-Blind Extension Period and Cross-Over Open Label
Extension Period
A set of safety summary tables will be produced to evaluate potential risks associated with 
the safety and tolerability of administering the study medication. All clinical AEs, SAEs, 
on-treatment AEs, 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, standard deviation etc.
Change from baseline on selected safety endpoints may be additionally summarized. Tier-1 
analyses will not be done for the Single-Blind Extension Period and Cross-Over Open Label
Extension Periods. 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 will be described in the SAP.
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9.5. Interim Analysis During the Treatment Period 
The statistical analysis plan and the interim analysis plan for this protocol may include an
interim analysis using SALT total for both 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 12 visit. Additional interim analyses may 
be performed based on emerging data. 
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 is based on predicted power conducted on a total of approximately 45 subjects who 
complete or had the chance to complete Week 12.  A non-informative prior will be used for 
the interim analysis.  The decision at the end of the study is being at least 90% confident that 
active treatment will be superior to placebo (DC1).
The study will be stopped for futility for that active treatment arm if predictive power of 
meeting DC1 at the end of study is <10% for that active arm. Due to the nature of the 
analyses the overall Type 1 error for the study is maintained.  If the futility condition is met 
for both active arms, the study will be stopped at the interim point.
The interim analysis results will be used to facilitate internal decision-making.  The results
will only be distributed to a select list of individuals involved in the internal decision-making
process in order to protect the integrity of the study.  This list of individuals will be provided
in the interim analysis plan.  The results of the interim analysis will not enable individuals
directly involved in running the study (such as investigators) to identify treatment
assignments for individual subjects still in the study.  There are no prospective plans to stop
the study early for success as a result of the interim analyses.
During the interim analysis, some members of the study team may be unblinded and replaced 
with blinded colleagues.  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 follow up period of the study.
9.6. 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 9.5.  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. 


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This study will utilize an independent separate Internal Review Committee to review the 
results of the interim analysis. Details of the logistics and operational aspects of the IA may
be documented in an IA charter.
The committee will have completed its work and been dissolved once the database lock and 
data release occurs for the initial 24-week Treatment Period and study team becomes 
unblinded. Unblinded study team will continue monitoring of the safety of subjects in the 
study.
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.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection. The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent. Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/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 


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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. 
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, 
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12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
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.


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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.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator 
will retain the original of each subject's signed consent document.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union (EU) is defined as the time at which it 
is deemed that a sufficient number of subjects have been recruited and completed the study 
as stated in the regulatory application (ie, clinical trial application [CTA]) and ethics 
application in the Member State.  Poor recruitment (recruiting less than the anticipated 
number in the CTA) by a Member State is not a reason for premature termination but is 
considered a normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV). 


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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.
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 EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements.  EU Basic Results are submitted for posting within 1 year 
of the PCD for studies in adult populations or within 6 months of the PCD for studies in 
pediatric populations.


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


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16. REFERENCES
1.
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Psychological Disorders in Patients with Alopecia Areata in Comparison with Normal 
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2.
Craiglow, B. G. and B. A. King (2014). "Killing Two Birds with One Stone: Oral 
Tofacitinib Reverses Alopecia Universalis in a Patient with Plaque Psoriasis." Journal 
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Dharnidharka, V. R., C. Kwon and G. Stevens (2002). "Serum cystatin C is superior to 
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Gilhar, A. (2010). "Collapse of Immune Privilege in Alopecia Areata: Coincidental or 
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Gilhar , A., A. Etzioni  and R. Paus (2012). "Alopecia Areata." New England Journal of 
Medicine 366(16): 1515-1525.
6.
Guttman-Yassky, E., B. Ungar, S. Noda, M. Suprun, A. Shroff, R. Dutt, S. Khattri, M. 
Min, Y. Mansouri, X. Zheng, Y. D. Estrada, G. K. Singer, M. Suarez-Farinas, J. G. 
Krueger and M. G. Lebwohl (2016). "Extensive alopecia areata is reversed by IL-12/IL-
23p40 cytokine antagonism." Journal of Allergy and Clinical Immunology 137(1): 
301-304.
7.
Harris, J. E., M. Rashighi, N. Nguyen, A. Jabbari, G. Ulerio, R. Clynes, A. M. 
Christiano and J. Mackay-Wiggan (2016). "Rapid skin repigmentation on oral 
ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA)." Journal of the 
American Academy of Dermatology 74(2): 370-371.
8.
Hoek, F. J., F. A. W. Kemperman and R. T. Krediet (2003). "A comparison between 
cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of 
glomerular filtration rate." Nephrology Dialysis Transplantation 18(10): 2024-2031.
9.
Hordinsky, M. K. (2013). "Overview of Alopecia Areata." Journal of Investigative 
Dermatology Symposium Proceedings 16(1): S13-S15.
10.
Inker , L. A., C. H. Schmid , H. Tighiouart , J. H. Eckfeldt , H. I. Feldman , T. Greene , 
J. W. Kusek , J. Manzi , F. Van Lente , Y. L. Zhang , J. Coresh  and A. S. Levey (2012). 
"Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C." New 
England Journal of Medicine 367(1): 20-29.
11.
Jabbari, A., Z. Dai, L. Xing, J. E. Cerise, Y. Ramot, Y. Berkun, G. A. M. Sanchez, R. 
Goldbach-Mansky, A. M. Christiano, R. Clynes and A. Zlotogorski (2015). "Reversal of 
Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib." 
EBioMedicine 2(4): 351-355.


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12.
King, B. (2016). Treating Alopecia Areata, Vitiligo and Atopic Dermatitis: JAK 
Inhibitors, Something New for Dermatology. American Academy of Dermatology 
Annual Meeting Washington, DC.
13.
Kroenke K, S. R. (2002). "The PHQ-9: A new depression diagnostic and severity 
measure." Psychiatric Annals., 32: 509-515.
14.
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.
15.
Mendoza, T. R., J. S. Osei, Q. Shi and M. Duvic (2013). "Development of the Alopecia 
Areata Symptom Impact Scale." Journal of Investigative Dermatology Symposium 
Proceedings 16(1): S51-S52.
16.
Murray, P. J. (2007). "The JAK-STAT signaling pathway: input and output integration." 
J Immunol 178(5): 2623-2629.
17.
Newman, D. J., H. Thakkar, R. G. Edwards, M. Wilkie, T. White, A. O. Grubb and C. 
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): 
312-318.
18.
O'Sullivan, L. A., C. Liongue, R. S. Lewis, S. E. Stephenson and A. C. Ward (2007). 
"Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease." 
Mol Immunol 44(10): 2497-2506.
19.
Olaharski, A. J., N. Gonzaludo, H. Bitter, D. Goldstein, S. Kirchner, H. Uppal and K. 
Kolaja (2009). "Identification of a Kinase Profile that Predicts Chromosome Damage 
Induced by Small Molecule Kinase Inhibitors." PLoS Computational Biology 5(7): 
e1000446.
20.
Olsen, E. A. (2011). "Investigative guidelines for alopecia areata." Dermatologic 
Therapy 24(3): 311-319.
21.
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.
22.
Phan, N. Q., C. Blome, F. Fritz, J. Gerss, A. Reich, T. Ebata, M. Augustin, J. C. 
Szepietowski and S. Stander (2012). "Assessment of pruritus intensity: prospective 
study on validity and reliability of the visual analogue scale, numerical rating scale and 
verbal rating scale in 471 patients with chronic pruritus." Acta Derm Venereol 92(5): 
502-507.


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23.
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.
24.
Suárez-Fariñas, M., B. Ungar, S. Noda, A. Shroff, Y. Mansouri, J. Fuentes-Duculan, A. 
Czernik, X. Zheng, Y. D. Estrada, H. Xu, X. Peng, A. Shemer, J. G. Krueger, M. G. 
Lebwohl and E. Guttman-Yassky (2015). "Alopecia areata profiling shows TH1, TH2, 
and IL-23 cytokine activation without parallel TH17/TH22 skewing." Journal of 
Allergy and Clinical Immunology 136(5): 1277-1287.
25.
Xing, L., Z. Dai, A. Jabbari, J. E. Cerise, C. A. Higgins, W. Gong, A. de Jong, S. Harel, 
G. M. DeStefano, L. Rothman, P. Singh, L. Petukhova, J. Mackay-Wiggan, A. M. 
Christiano and R. Clynes (2014). "Alopecia areata is driven by cytotoxic T lymphocytes 
and is reversed by JAK inhibition." Nature medicine 20(9): 1043-1049.
26.
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.
27.
Andreotti, A. H., P. L. Schwartzberg, R. E. Joseph and L. J. Berg (2010). "T-Cell 
Signaling Regulated by the Tec Family Kinase, Itk." Cold Spring Harbor Perspectives 
in Biology 2(7): a002287.
28.
Atherly, L. O., M. A. Brehm, R. M. Welsh and L. J. Berg (2006). "Tec Kinases Itk and 
Rlk Are Required for CD8&lt;sup&gt;+&lt;/sup&gt; T Cell Responses to Virus 
Infection Independent of Their Role in CD4&lt;sup&gt;+&lt;/sup&gt; T Cell Help." 
The Journal of Immunology 176(3): 1571.
29.
Bao, Y., J. Zheng, C. Han, J. Jin, H. Han, Y. Liu, Y.-L. Lau, W. Tu and X. Cao (2012). 
"Tyrosine Kinase Btk Is Required for NK Cell Activation." The Journal of Biological 
Chemistry 287(28): 23769-23778.
30.
Ito, T., N. Ito, M. Saatoff, H. Hashizume, H. Fukamizu, B. J. Nickoloff, M. Takigawa 
and R. Paus (2008). "Maintenance of Hair Follicle Immune Privilege Is Linked to 
Prevention of NK Cell Attack." Journal of Investigative Dermatology 128(5): 
1196-1206.
31.
Kurosaki, T. (2011). "Regulation of BCR signaling." Molecular Immunology 48(11): 
1287-1291.
32.
Suárez-Fariñas, M., B. Ungar, S. Noda, A. Shroff, Y. Mansouri, J. Fuentes-Duculan, A. 
Czernik, X. Zheng, Y. D. Estrada, H. Xu, X. Peng, A. Shemer, J. G. Krueger, M. G. 
Lebwohl and E. Guttman-Yassky (2015). "Alopecia areata profiling shows TH1, TH2, 
and IL-23 cytokine activation without parallel TH17/TH22 skewing." Journal of 
Allergy and Clinical Immunology 136(5): 1277-1287.


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33.
Thomis, D. C. and L. J. Berg (1997). "Peripheral Expression of Jak3 Is Required to 
Maintain T Lymphocyte Function." The Journal of Experimental Medicine 185(2): 197-
206.
34.
Xing, L., Z. Dai, A. Jabbari, J. E. Cerise, C. A. Higgins, W. Gong, A. de Jong, S. Harel, 
G. M. DeStefano, L. Rothman, P. Singh, L. Petukhova, J. Mackay-Wiggan, A. M. 
Christiano and R. Clynes (2014). "Alopecia areata is driven by cytotoxic T lymphocytes 
and is reversed by JAK inhibition." Nature medicine 20(9): 1043-1049.


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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
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AT
active treatment
ATP
adenosine triphosphate
AUC
area under the concentration-time curve 
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
 
BCG
bacille calmette guérin 
BID
twice a day
BP
blood pressure
BUN
blood urea nitrogen
CDS
core data sheet
CK
creatine kinase
CL
clearance
Cmax
maximum plasma concentration
CMV
cytomegalovirus 
CO
cross-over
COEOT
cross-over end of treatment
CRF
case report form
CSA
clinical study agreement
CsA
cyclosporine A 
CSF
cerebrospinal fluid
CSR
clinical study report
CT
computed tomography
CTA
clinical trial application
CTCAE
common terminology criteria for adverse events
DAI
dosage and administration instructions
DDI
drug-drug interaction
CCI
CCI
CCI


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Abbreviation
Term
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
EFD
embryo-fetal development
eGFR
estimated glomerular filtration rate 
ELISA
enzyme-linked immunosorbent assay 
EOS
end of study
EOT
end of treatment
EPO
erythropoietin
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
FACS
fluorescence-activated cell sorting
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 
GM-CSF
granulocyte-macrophage colony-stimulating factor
GST
glutathione-S-transferase 
HBcAb
hepatitis B core antibody 
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen 
HCVAb
hepatitis C antibody
HEENT
head, eyes, ears, nose and throat
HIV
human immunodeficiency virus
HRQL
health-related quality of life
HSV
herpes simplex virus
IB
investigator’s brochure
ICH
International Conference on Harmonisation
ID
identification
IFNα
interferon alfa
CCI
CCI
CCI


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Abbreviation
Term
IFNγ
interferon gamma
Ig
Immunoglobulin
IGA
investigator’s global assessment
IGRA
Interferon Gamma Release Assay
IgE
immunoglobulin E
IL
interleukin 
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
IRT
interactive response technology
IUD
intrauterine device
IVRS
interactive voice response system
IWR
interactive web response
JAK
janus kinase
LFT
liver function test
LLN
lower limit of normal 
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/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 
NK
natural killer cells
NOAEL
no observed adverse effect level 
NRI
non-responder imputation
OAT2
organic anion transporter 2
OBU
oncology business unit
OCT2
organic cation transporter 2 
PCD
primary completion date
PD
pharmacodynamic
PI
principal investigator
PFS
pre-filled syringe
CCI
CCI


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Abbreviation
Term
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
PT
prothrombin time
PtGA
patient global assessment 
QD
once daily
QFT-G
QuantiFERON-TB Gold 
QFT-GIT
QuantiFERON-TB Gold In-Tube 
Rac
accumulation ratio 
RNA
ribonucleic acid
RRCK
ralph russ canine kidney cells
SAD
single ascending dose
SAE
serious adverse event
SALT
severity of alopecia tool
SAP
statistical analysis plan
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
SRSD
single reference safety document
SSC
special safety concern 
STATs
signal transducers and activators of transcription
t½
half life
TB
tuberculosis 
TBNK
T, B, and natural killer cells
TDAR
T cell-dependent antibody response
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


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Abbreviation
Term
USPI
United States package insert
UVA
ultraviolet A light
UVB
ultraviolet B light
UVR
ultraviolet radiation
VZV
varicella zoster virus


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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 
inhibitor
s
Substrate
s of 
MDR1 
Substrates of 
OCT2/MAT
E
Amprenavir
Avasimibe#
Simvastatin or 
Simvastatin-containin
g products
Quinidine
Digoxin
Dofetilide
Amiodarone 
Bosentan
Aprepitant
Barbiturates
Atazanavir
Carbamazepine
#
Boceprevir
Efavirenz 
Casopitant
Etravirine
Cimetidine
Mitotane#
Ciprofloxacin
Modafinil
Clarithromycin#
Nafcillin
Cobicistat#
Phenobarbital#
Conivaptan#
Phenytoin#
Darunavir
Rifabutin#
Diethyldithiocarbamat
e
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#


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Tipranavir#
Tofisopam
Troleandomycin#
Verapamil
Voriconazole#
* 
All prohibited drugs that are CYP3A inhibitors require at least a 7 day or 5 half-lives (whichever is 
longer) prior to the first dose of study drug.  Note: Amiodarone requires discontinuation at least 290 days 
(~5 half-lives, half-life averages ~58 days) prior to the first dose of study drug.
** 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 study drug.
# 
Noted as potent inhibitors or inducers. 
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 3. Severity of Alopecia Tool (SALT) 
(Olsen 2011)20
SALT score= 0.18×score_left side + 0.18×score_right side + 0.4×score_top + 
0.24×score_back
For example:


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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 6. Guidelines for Subject Safety Monitoring and Discontinuation
These guidelines for subject safety monitoring and discontinuation are to be applied to all 
subjects in study B7931005.  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 6.1. 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 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 6.2. Discontinuation
Treatment will be discontinued and the subject withdrawn from this study for:
Adverse Events:

Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization;

Clinically meaningful, treatment related decline in hearing from baseline.

Other serious or severe AEs, at the discretion of the investigator or sponsor.
Potential Cases of Potential Drug-Related Rash:

Serious or severe drug-related rash at the discretion of the investigator or sponsor 
(Appendix 4). 


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Potential Cases of Decreased eGFR:
If an individual subject demonstrates a CONCOMITANT serum creatinine-based AND 
serum Cystatin C-based eGFR decline of 30% compared to the subject’s baseline eGFR, 
then the subject should not be further dosed and adequate, immediate, supportive measures 
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 then 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 P (see 
protocol Section 8.4.3).
Psychological Assessment
At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any behavioral 
question of the C-SSRS, the subject will be discontinued from the study and referred to a 
mental health professional for appropriate evaluation and treatment.  If the 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.
Laboratory Abnormalities:
All the following laboratory abnormalities require discontinuation if they are confirmed.  
Confirmation through re-testing should occur within 1 week:


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Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil Count
<1000/mm3; <1.0 x109/L
Hemoglobin
<8.0 g/dL; <4.96 mmol/L; <80 g/L
Platelet count
<75,000/mm3; <75.0x109/L
Lymphocytes
<500/mm3; <0.5x109/L
Chemistry
AST
>2.5x ULN
ALT
>2.5x ULN
Total bilirubina
>1.5x ULN
CK
>10x ULN
a
Total bilirubin 1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin 
measured and would be eligible for this study provided the direct bilirubin is ULN.
Discontinuation/End of Treatment Monitoring:
Any subject meeting discontinuation criteria must enter into the Follow-up Period with their 
first follow-up visit occurring 1 week after their last dose whenever possible, until the event 
has returned to normal or baseline levels or is deemed clinically stable.  The procedures 
scheduled for 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.  Additional follow-up visits may occur 
as needed until any clinically relevant abnormalities or adverse events have resolved, 
returned to a baseline state, or are deemed clinically stable.


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Appendix 9. Suicidal Behaviors Questionnaire-Revised (SBQ-R) 
(Osman, Bagge et al. 2001)21


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Appendix 10. Patient Health Questionnaire – 8 items (PHQ-8) 
(Kroenke K 2002)13


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SAP_001.pdf: 
Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 1
Protocol B7931005
PHASE 2A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY
PROFILE OF PF-06651600 AND PF-06700841 IN SUBJECTS WITH MODERATE
TO SEVERE ALOPECIA AREATA WITH A SINGLE-BLIND EXTENSION 
PERIOD AND A CROSS-OVER OPEN LABEL EXTENSION PERIOD
Statistical Analysis Plan 
(SAP)
Version:
4 (Amendment 3)
Date:
12-JUN-2018


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 2
TABLE OF CONTENTS 
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
1. VERSION HISTORY............................................................................................................6
2. INTRODUCTION .................................................................................................................9
2.1. Study Objectives and Endpoints During Treatment Period ......................................9
2.2. Study Objectives and Endpoints During Single-Blind Extension Period ...............12
2.3. Study Objectives and Endpoints during Cross-Over Open Label Extension 
Period.........................................................................................................................14
2.4. Study Design ...........................................................................................................16
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................23
3.1. Primary Endpoint(s) ................................................................................................23
3.2. Secondary Efficacy Endpoint(s)..............................................................................23
3.3. Exploratory Efficacy Endpoint(s) ...........................................................................24
3.5. Baseline Variables...................................................................................................26
3.6. Safety Endpoints .....................................................................................................26
3.6.1. Adverse Events...........................................................................................26
3.6.2. Laboratory Data..........................................................................................27
3.6.3. Vital Signs ..................................................................................................29
3.6.4. Electrocardiograms.....................................................................................29
4. ANALYSIS SETS ...............................................................................................................29
4.1. Full Analysis Set .....................................................................................................29
4.2. Safety Analysis Set..................................................................................................29
4.3. Other Analysis Sets .................................................................................................29
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................29
5.1. Hypotheses and Decision Rules ..............................................................................30
5.2. General Methods .....................................................................................................30
5.2.1. Analyses for Binary Data............................................................................30
5.2.2. Analyses for Continuous Data....................................................................31
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Statistical Analysis Plan, Amendment 3
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5.3. Methods to Manage Missing Data ..........................................................................31
6. ANALYSES AND SUMMARIES ......................................................................................32
6.1. Analyses and Summaries During the Treatment Period .........................................32
6.1.1. Primary Endpoint(s)....................................................................................32
6.1.1.1. Change from Baseline for SALT score.....................................32
6.1.2. Secondary Endpoint(s)................................................................................33
6.1.2.1. SALT 30....................................................................................33
6.1.2.2. Change from Baseline in Investigator Global Assessment 
(IGA) .................................................................................................34
6.1.2.3. SALT 50, SALT 75, SALT 90 and SALT 100 .........................34
6.1.2.4. Percentage change in SALT......................................................34
6.1.4. Subset Analyses..........................................................................................38
6.1.5. Baseline and Other Summaries and Analyses ............................................38
6.1.5.1. Baseline Summaries ..................................................................38
6.1.5.2. Study Conduct and Subject Disposition....................................38
6.1.5.3. Study Treatment Exposure and Compliance.............................38
6.1.5.4. Concomitant Medications and Non-Drug Treatments ..............39
6.1.6. Safety Summaries and Analyses.................................................................39
6.1.6.1. Adverse Events..........................................................................39
6.1.6.2. Laboratory Data.........................................................................39
6.1.6.3. Vital Signs.................................................................................40
6.1.6.4. Electrocardiogram .....................................................................40
6.1.6.5. Physical Examination................................................................41
6.2. Analyses and Summaries During the Single-Blind Extension Period ....................41
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Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 4
6.2.1. Primary Endpoints (Safety) ........................................................................42
6.2.2. Exploratory Efficacy Analysis....................................................................42
6.2.2.1. Continuous Endpoints ...............................................................42
6.2.2.2. Binary Endpoints.......................................................................45
6.2.2.4. Placebo Treatment Duration: Time to Event (Retreatment) 
and Change from Baseline for Single-Blind Extension in SALT
Endpoints...........................................................................................48
6.3. Analyses and Summaries During the Cross-over Open-Label Extension 
Period.........................................................................................................................50
6.3.1. Primary Endpoints (Safety) ........................................................................50
6.4. Interim Clinical Study Report .................................................................................51
7. INTERIM ANALYSES.......................................................................................................51
7.1. Introduction .............................................................................................................51
7.2. Interim Analyses and Summaries............................................................................52
8. REFERRENCES..................................................................................................................53
9. APPENDICES .....................................................................................................................54
LIST OF TABLES
Table 1.
Rationale of Major Changes in SAP Amendments ................................................6
Table 2.
IGA Score .............................................................................................................24
Table 5.
Laboratory Tests ...................................................................................................28
Table 6.
Laboratory Re-Testing Criteria.............................................................................40
Table 7.
Laboratory Abnormality Criteria..........................................................................40
LIST OF FIGURES
Figure 1.
Design Schematic .................................................................................................17
APPENDICES
Appendix 1. Summary of Efficacy Analyses...........................................................................54
Appendix 1.1. Summary of Efficacy Analyses in the Treatment Period.................................54
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Statistical Analysis Plan, Amendment 3
Page 5
Appendix 1.2. Summary of Efficacy Analyses in the Single-Blind Extension Period............57
Appendix 2. Data Derivation Details.......................................................................................59
Appendix 2.1. Definition and Use of Visit Windows in Reporting the Initial Treatment 
Period....................................................................................................................59
Appendix 2.2. Definition and Use of Visit Windows in Reporting the Single-Blind 
Extension Period...................................................................................................59
Appendix 3. Statistical Methodology Details of Delta Method...............................................61
Appendix 4. Criteria for Treatment Assignment/Subject Retreatment during the 
Extension Periods .................................................................................................63
Appendix 5. Severity of Alopecia Tool (SALT) .....................................................................66
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Page 6
1. VERSION HISTORY
This Statistical Analysis Plan (SAP) for study B7931005 is based on the Protocol
Amendment 4 dated 6 June 2018. 
Table 1.
Rationale of Major Changes in SAP Amendments
SAP Version
Change
Rationale
1
Not Applicable
Not Applicable
2

Updated study design.

Added details of the analyses 
required during the extension 
phase.
This SAP amendment is to 
support Protocol Amendment 3.
3

In Section 3.2 “Secondary 
Efficacy Endpoint(s)”, added that 
SALT 90 may be analyzed.

In Section 5.2.1 “Analyses for 
Binary Data”, removed multiple 
imputation for binary data.
Additionally, clarified that the 
exact method used for binary data 
would be based on 
Non-Responder imputation.

In Section 5.2.2 “Analyses for 
Continuous Data”, added texts 
“for the primary endpoint” in
the sentence “Sensitivity analyses 
for the primary endpoint will be 
completed using multiple 
imputation methods as described 
in Section 5.3.”; added a second
sensitivity analysis for primary 
endpoint, which is to fit a linear 
mixed effect model for 
longitudinal data using visit as 
continuous variable.

Removed Section 5.2.3 “Analyses 

To support the 
understanding of binary 
variables defined based on 
SALT score since it is 
believed by investigators 
that SALT 90 is regarded as 
achieving remission.

To be clear that binary data 
will be analyzed using 
GLMM method on observed 
data and exact test method
on NRI data.

To be clear that multiple 
imputation will be used for 
primary endpoint as a
sensitivity analysis. The 
addition of a second 
sensitivity analysis is to help
investigate if time on 
treatment has linear effect 
on the primary endpoint.

To clarify the analysis 


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 7
for Categorical Data”, and added 
texts regarding analysis method 
for ordinal categorical data in 
Section 5.2.1, which says ordinal
data, like
will be 
transformed to binary data for 
statistical analysis and be 
summarized with proportions by 
each category.
•
In Section 5.3 “Methods to 
Manage Missing Data”, deleted 
stepwise selection for selecting 
covariates to be used in multiple 
imputation and clarified that 
treatment, visit, baseline SALT 
score, and possibly duration since 
onset of current episode would be 
used as imputation covariates
based on regression method 
(instead of propensity method); in 
addition, deleted multiple 
imputation for binary data 
including SALT 30, SALT 50, 
SALT 75, SALT 100.
•
In Section 6 “Analyses and
Summaries’, clarified the “95% 
confidence interval” to be “95% 
2-sided confidence interval” for 
primary endpoint, and clarified 
the “90% 2-sided confidence 
interval” for secondary and other 
endpoints.
 
 
 
 
•
In Section 6.1.7.1 “Safety 
Summaries and Analyses” during 
Treatment Period, added that 
summary tables of TEAE by 
system organ class and preferred 
method for ordinal data.
•
To clarify the covariates, 
method, and endpoints to be 
used with multiple 
imputation.
•
To clarify the level of
confidence levels for
different endpoints. 
•
To support the 
understanding of itchy 
scalp.
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to be generated separately for 
induction phase and maintenance
phase.

In Section 6.2 “Analyses and 
Summaries During Extension 
Period”, clarified that efficacy 
endpoints will be presented by 
visit and the treatment routes. The 
possible treatment routes subjects 
may go through in the Extension 
Period were listed based on the 
study design.

In Sections 6.2.2.1 and 6.2.2.2, 
updated that the active vs.
placebo comparisons in both the 
Treatment Period and the 
Extension Period will be 
presented in the same figure, and 
the x-axis for presenting visits in 
Extension Period will be shifted 
to align with Treatment Period, 
ie, Week 2/ Week 30, Week 30 / 
AT Week 2 …etc.

In Section 6.2.2.4, added analysis 
of change from baseline in SALT 
for subjects who are treated with 
Placebo in Extension Period.

Updated Appendix 1 “Summary 
of Efficacy Analyses” according 
to above edits and added a table 
for efficacy analyses during 
Extension Period in Appendix 
1.2.

Updated Appendix 4 “Criteria for 
Treatment Assignment during the 
Extension Period” by adding 
sections 3 and 4 based on the 
latest Communication Plan .

To clarify the treatment 
groups in efficacy analyses
in the Extension Period.

To compare the efficacy in 
Treatment Period and 
Extension Period.

To support understand the 
change in the hair volume 
after subjects stopped active 
treatment.
4

Updated study title, and study 
objectives in Section 2.3 and 2.4
based on the update in the 

To be consistent with the 
protocol amendment 4.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 9
protocol amendment 4.
•
Updated “Extension Period” to be 
“Single-Blind Extension Period”
according to the name change in 
the protocol amendment 4 for the 
first Extension Period. 
 
•
Added Section 6.3 for the 
analyses during the cross-over 
open label extension period.
•
Added Section 6.4 about interim 
clinical study report.
•
To reflect the addition of 
this period in the protocol 
amendment 4.
•
To specify that an interim 
clinical study report is 
planned after the 24-week 
Treatment Period is 
completed.
2. INTRODUCTION
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study B7931005.  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 Treatment Period
Primary Objective:
Primary Endpoint:
•
To evaluate the efficacy of PF-06651600 
and PF-06700841 compared to placebo at 
Week 24 in adult subjects with moderate 
to severe alopecia areata.
•
Change from baseline of Severity of 
Alopecia Tool (SALT) score at 
Week 24. 
Secondary Objectives:
Secondary Endpoints:
Key Secondary Efficacy Objective: 
•
To evaluate the effect of PF-06651600 
and PF-06700841 on SALT 30 at 
Week 24 in adult subjects with moderate 
to severe alopecia areata.
Key Secondary Efficacy Endpoint:
•
Proportion of subjects achieving a 30% 
improvement in SALT (SALT 30) at 
Week 24.  
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Other Secondary Efficacy Objectives:

To evaluate the effect of PF-06651600 
and PF-06700841 on additional efficacy 
endpoints over time in adult subjects 
with moderate to severe alopecia areata 
in the Treatment Period.
Other Secondary Efficacy Endpoints:

Change from baseline in Investigator 
Global Assessment (IGA) at all time 
points up to Week 24 as specified in the 
Schedule of Activities (SoA).

Change from baseline in SALT at 
intermediate time points up to Week 24 
as specified in the SoA.

Proportion of subjects achieving a 30% 
improvement in SALT (SALT 30) at 
intermediate time points up to Week 24 
as specified in the SoA except for 
Week 24. 

Proportion of subjects achieving a 
50%, 75% and 100% improvement in 
SALT (SALT 50, SALT 75, and 
SALT 100) at all time points up to 
Week 24 as specified in the SoA.

Percentage change in SALT from 
baseline to Week 24 at intermediate 
time points as specified in the SoA.
Safety Objectives:

To evaluate the safety and tolerability of 
PF-06651600 and PF-06700841 over 
time in adult subjects with moderate to 
severe alopecia areata in the Treatment 
Period.
Safety Endpoints:

Incidence of treatment-emergent 
adverse events (AEs) 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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2.2. Study Objectives and Endpoints During Single-Blind Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and tolerability 
of PF-06651600 and PF-06700841 over 
time in adult subjects with moderate to 
severe alopecia areata during the 
Single-Blind Extension Period.
•
Incidence of treatment-emergent adverse 
events (AEs) during the Single-Blind 
Extension Period.
•
Incidence of specific clinical laboratory 
abnormalities including but not limited to 
anemia, neutropenia, thrombocytopenia, 
lymphopenia, changes in lipid profile, 
and liver function tests (LFTs) during the 
Single-Blind Extension Period.
 
 
 
•
Change from baseline in SALT during 
the Single-Blind Extension Period at all 
time points as specified in the SoA.
•
Proportion of subjects achieving 
SALT 30 during the Single-Blind 
Extension Period at all time points as 
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specified in the SoA. 
•
Proportion of subjects achieving 
SALT 50, SALT 75, SALT 100 during 
the Single-Blind Extension Period at all 
time points as specified in the SoA. 
 
•
Time to achieve the retreatment criteria 
during the Withdrawal/Retreatment part 
of the Extension Period among subjects 
who achieved primary endpoint at Week 
24.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.3. Study Objectives and Endpoints during Cross-Over Open Label Extension Period
Primary Objective:
Primary Endpoint:
•
To evaluate the safety and 
tolerability of PF-06651600 and 
PF-06700841 over time in subjects 
who are non-responders to 
PF-06700841 and PF-06651600, 
respectively, during the Cross-Over 
Open Label Extension period.
•
Incidence of treatment-emergent adverse 
events (AEs) during the Cross-Over Open 
Label Extension period.
•
Incidence of specific clinical laboratory 
abnormalities including but not limited to 
anemia, neutropenia, thrombocytopenia, 
lymphopenia, changes in lipid profile, and 
liver function tests (LFTs) during the 
Cross-Over Open Label Extension Period.
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2.4. Study Design
Study B7931005 will investigate the JAK3 inhibitor PF-06651600 and TYK2/JAK1 inhibitor 
PF-06700841 in alopecia areata (AA). This is a Phase 2a, randomized, double-blind, parallel 
group, multicenter study with two Extension Periods. The study will have a maximum 
duration of approximately 113 weeks. This includes an up-to-5-week screening period, a 
24-week Treatment Period, a 4-week Drug Holiday #1, an up-to-12-month Single-Blind 
(sponsor open, investigator open and subject blind) Extension Period, a 4-week Drug Holiday 
#2, a 6-month Cross-Over Open Label Extension Period and a 4-week Follow-up Period.
The study will enroll a total of approximately 132 subjects. The study will be conducted at 
approximately 30 to 40 sites.
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Statistical Analysis Plan, Amendment 3
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Figure 1.
Design Schematic
Drug 
Holiday #1
4 weeks
Placebo, n=22*
PF-06651600, n =44
Induction
4 weeks
Maintenance
20 weeks
Biopsy Sub-study (selected sites)
Treatment Period only
PF-06700841, n= 44
60 mg
30 mg
200 mg
50 mg
* During the data analysis, the placebo groups will be combined in 
Treatment Period
Placebo, n=22*
Treatment Period 
24 weeks
Screening
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Statistical Analysis Plan, Amendment 3
PFIZER CONFIDENTIAL
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Sponsor open, investigator open, subject blind.
# All subjects who complete the initial 24-week Treatment Period will be evaluated for potential entry into the Single-Blind Extension Period during the Drug Holiday #1.  Subjects will enter the 
Single-Blind Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s entrance in the Single-Blind Extension 
Period. Subjects will be assigned by the study designee(s) to receive either active treatment (PF-06651600 or PF-06700841) to start the segment of non-responders or placebo at Week 28 (after the 
4-week Drug Holiday #1) to start the Withdrawal/Retreatment segment for responders.
+ Subjects who are assigned to the placebo group will receive placebo for up to 24 weeks until they meet the retreatment criteria described in the SAP.  Subjects who meet the criteria will receive the 
same respective active compound (PF-06651600 or PF-06700841), dose, and treatment duration as the original treatment which consists of a 4-week induction period and a 20-week maintenance 
period, providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation (audiogram result available within 8 weeks is 
acceptable).  Subjects who do not meet the retreatment criteria throughout the 24 weeks will go directly to the EOS visit. Subjects who complete the Withdrawal/Retreatment segment will go 
directly to the Follow-up and will not participate in the Cross-Over Open Label Extension Period.
* Retreatment criteria will be described in the SAP.  The study designee(s), who are independent of the study team, will inform the site if the subject meets the  criteria to start active treatment, 
providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s participation (audiogram result available within 8 weeks is acceptable).
Single-BlindExtension Period
Cross 
Over 
Open 
Label
EOS
Drug 
Holiday 
#1
4 weeks# 
N
Do not meet retreatment criteria 
throughout 24 weeks
Placebo+
Meets 
Retreatment 
Criteria *
Y
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
Segment for Non-responder
PF-06651600, n66
200 mg
50 mg
60 mg
30 mg
PF-06700841, n≤66
Induction
4 weeks
Maintenance 20 weeks
Withdrawal / Retreatment Segment for Responder
FU 
Period


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 19
Cross-Over Open Label Extension Period
PF-06651600
Non-responder
PF-06700841
Non-responder
Y
60 mg
30 mg
PF-06700841, n≤ 66
Induction
4 weeks
Maintenance 20 
weeks
Follow up 
4 weeks
N
* All subjects who are assigned to receive active treatment (PF-06651600 or PF-06700841) directly and complete the segment for non-responder in Single-
Blind Extension Period may be evaluated for potential entry into the Cross-Over Open Label Extension Period during the Drug Holiday #2.  Subjects will 
enter the Cross-Over Open Label Extension Period providing none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Cross-Over Open Label Extension Period as well as the non-responder criteria is met at Week 52.  
Meet  non-
responder 
criteria? *
Drug 
Holiday 
#2 
4 weeks*
PF-06651600, n66
200 mg
50 mg
Induction
4 weeks
Maintenance 20 
weeks


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 20
Subjects who have moderate to severe alopecia areata (50% hair loss of the scalp [SALT 
score 50] without evidence of hair regrowth within the previous 6 months; current episode 
of fixed hair loss 7 years) present at the screening and baseline visits will be included in the 
study. Photographs will be taken at the Screening Visit to verify eligibility (50% hair loss 
of the scalp). Subjects will be randomized to PF-06651600 or matching placebo in a 
2:1 ratio or to PF-06700841 or matching placebo in a 2:1 ratio. During the data analysis for 
the initial Treatment Period, placebo groups will be combined to yield final investigational 
product: placebo ratios of 1:1:1 for each investigational product. Investigators, subjects, and 
the sponsor study team will be blinded as to treatment group. 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 in the interim CSR and published once the last subject 
last visit occurs for the initial 24-week Treatment Period. The interim study report may be 
shared with the principal investigator (PI) when it is available. 
Subjects will be screened within 35 days prior to the first dose of study drug to confirm that 
they meet the subject selection criteria for the study. The initial 24-week treatment consists 
of a 4-week induction treatment period and a 20-week maintenance treatment period.
An induction dose of 200 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD 
for 20 weeks of PF-06651600, an induction dose of 60 mg QD for 4 weeks followed by 
maintenance dosing of 30 mg QD for 20 weeks of PF-06700841, and matching placebo will 
be investigated.
A biopsy sub-study will be performed at selected sites only during the initial 24 weeks of the 
study.  Approximately 42 subjects will be randomized (expected to provide approximately 
30 completers). Subjects will be randomized to PF-06651600 or matching placebo in a 
2:1 ratio or PF-06700841 or matching placebo in a 2:1 ratio. During the data analysis for the 
biopsy sub-study, placebo groups will be combined to yield final investigational product: 
placebo ratios of 1:1:1 for each investigational product.
Single-Blind Extension Period
Alopecia Areata is a disease with high unmet medical need. Currently there are no approved 
medications for treatment of AA. A Single-Blind Extension Period has been added to this 
study to evaluate additional safety and tolerability of PF-06651600 and PF-06700841. The 
Extension Period will become Single-Blind (investigator open, sponsor open and subject 
blind) upon approval of amendment 4.
The Single-Blind Extension Period will provide an opportunity for subjects to receive 
additional active study treatment. It will start after a 4-week Drug Holiday #1. The duration 
of the Single-Blind Extension Period can be up to 12 months. Only subjects who complete 
Week 24 of the initial Treatment Period may be considered for eligibility to enter the 
Single-Blind Extension Period. Subjects who discontinue during the initial Treatment Period
will enter the 4-week Follow up Period and will not be eligible for the Single-Blind
Extension Period.  


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 21
All subjects who complete the initial 24-week Treatment Period will be evaluated during the 
Drug Holiday #1 for potential entry into the Single-Blind Extension Period. After the 
4-week Drug Holiday #1,  subjects will enter the Single-Blind Extension Period providing 
none of the Exclusion criteria #9, #10, and #26 (see Appendix 4) are met and the audiogram 
result does not preclude patient’s entrance in the Single-Blind Extension Period. Subjects 
who meet Exclusion criteria #9, #10, or #26 will be discontinued and enter the Follow-up 
Period.At Week 28 (after the 4-week Drug Holiday #1 that follows completion of Week 24), 
subjects will be assigned by the study designee(s) to receive either active treatment 
(PF-06651600 or PF-06700841) to start the segment for non-responder or placebo to start the 
Withdrawal/Retreatment segment for responder. The detailed criteria for treatment 
assignment is described in Appendix 4. The study designee(s), who are independent of the 
study team, will provide the site with a treatment assignment when IP is being supplied via 
the IRT system post Week 24. A detailed communication plan will be provided to the site. 
The probability to receive active treatment in the Single-Blind Extension Period is 
approximately 33% to 100%. All patients in the placebo group during the Treatment Period 
who are eligible for the Extension Period will be assigned to active treatment. During the 
Single-Blind Extension Period, all the subjects assigned to placebo at Week 28 will have a 
probability of 100% to receive active treatment if they meet the  retreatment criteria outlined 
in Appendix 4. 
During the Single-Blind Extension Period, subjects who are assigned to the active treatment 
(PF-06651600 or PF-06700841) at Week 28 to start the segment for non-responder will 
receive the same respective active compound (PF-06651600 or PF-06700841), dose, and 
treatment duration (a 4-week Induction Period and a 20-week Maintenance Period) as the 
original Treatment Period. 
Subjects who are assigned to the placebo group at Week 28 to start the 
Withdrawal/Retreatment segment will receive placebo for up to 24 weeks until they meet the 
retreatment criteria described in Appendix 4. These subjects will be assessed every 2 weeks 
during the first 8 weeks and then every 4 weeks up to 24 weeks by the study designee(s).
The study designee(s), who are independent of the study team, will inform the site if the 
subject meets the criteria to start active treatment. Subjects who meet the criteria will receive 
the same respective active compound (PF-06651600 or PF-06700841), dose, and treatment 
duration as the original treatment which consists of a 4-week induction period and a 20-week 
maintenance period, providing none of the Exclusion criteria #9, #10, and #26 are met and 
the audiogram result does not preclude patient’s participation (audiogram result available 
within 8 weeks is acceptable). Subjects who meet Exclusion criterion #9, #10, or #26 will be 
discontinued from the Single-Blind Extension Period and will go directly to the EOS visit. 
Subjects who do not meet the retreatment criteria for initiation of active treatment throughout 
the 24-week period (Week 28 to Week 52) will go directly to the EOS visit. Subjects who 
complete the Withdrawal/Retreatment segment will go directly to the Follow-up Period and 
will not participate in the Cross-Over Open Label Extension Period.
Any subject that has completed the initial 24 weeks of the Protocol B7931005 prior to the 
Protocol Amendment 3 availability is eligible for evaluation for potential enrollment into the 
Single-Blind Extension Period. Subjects are to be discussed with the sponsor for possible 
enrollment for the Single-Blind Extension Period.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 22
Cross-Over Open Label Extension Period
A 24 week Cross-Over Open Label Extension Period has been added to this study to evaluate 
safety and efficacy of PF-06651600 and PF-06700841 in subjects who complete the segment 
for non-responder in Single-Blind Extension Period and did not respond to the initial active 
treatment. More specifically, subjects who are PF-06651600 non-responder at Week 52 will 
receive PF-06700841 in the Cross-Over Open Label Extension Period. Subjects who are
PF-06700841 non-responder at Week 52 will receive PF-06651600 in the Cross-Over Open 
Label Extension Period. The subjects who were responders at Week 52 will enter the 
Follow-up Period directly. Non-responders are defined as subjects who have not achieved 
30% improvement in SALT relative to the baseline of the Treatment Period at Week 52. 
All subjects who complete the segment for non-responder in Single-Blind Extension Period 
and are non-responders will be evaluated during the Drug Holiday #2 for potential entry into 
the Cross-Over Open Label Extension Period.  After the 4-week Drug Holiday #2, subjects 
will enter the Cross-Over Open Label Extension Period providing none of the Exclusion 
criteria #9, #10, and #26 are met and the audiogram result does not preclude patient’s 
entrance in the Cross-Over Open Label Extension Period as well as the non-responder 
criteria is met at Week 52. Audiogram result available within 8 weeks is acceptable.
Subjects who meet Exclusion criteria #9, #10, or #26 will enter the Follow-up Period
directly. Subjects who do not meet the non-responder criteria at Week 52 will be informed 
by the study designee(s) during the Drug Holiday #2 and go directly to the Follow-up Period. 
Subjects who discontinue during the Single-Blind Extension Period will enter the 4-week 
Follow-up Period and will not be eligible for the Cross-Over Open Label Extension Period.  
At Cross-Over Open Label Day 1 (after the 4-week Drug Holiday #2 that follows completion 
of Single-Blind Extension Period), non-responders will be assigned to receive either 
PF-06651600 or PF-06700841(the opposite of the assigned treatment in the initial 24 weeks 
and Single-Blind Extension Period).  
During the Cross-Over Open Label Extension Period, subjects will receive an induction dose 
of 200 mg QD for 4 weeks followed by maintenance dosing of 50 mg QD for 20 weeks of 
PF-06651600 or an induction dose of 60 mg QD for 4 weeks followed by maintenance 
dosing of 30 mg QD for 20 weeks of PF-06700841. 
Any subject who has completed the segment for non-responder in Single-Blind Extension 
Period prior to protocol Amendment 4 initiation at the investigator site is eligible for 
evaluation for potential enrollment into the Cross-Over Open Label Extension Period.  These 
subjects are to be discussed with the sponsor prior to any possible enrollment into the 
Cross-Over Open Label Extension Period.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 23
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
The primary endpoint for this study is change from baseline of SALT score at Week 24.  
SALT is collected at all study visits.  Baseline is defined as the last measurement prior to 
randomization (Day 1). Change from baseline is defined as the baseline value minus the 
value at a specific visit.  Positive change from baseline signifies an improvement.
SALT is a quantitative assessment of AA severity based on scalp hair loss. A visual aid 
showing the division of the scalp hair into four quadrants, back, top of scalp, and both sides, 
with each of the four quadrants given an accurate determination of the % of scalp surface
area covered, representing 24%, 40%, 18%, and 18% of the total scalp surface area. Score 
parameters are detailed in Appendix 5. For any male subject, the male pattern alopecia 
should be permitted to score SALT equal to 0 at the end of trial.
3.2. Secondary Efficacy Endpoint(s)
The percent change from baseline will be calculated as baseline value – value at a specific 
visit divided by baseline and multiplied by 100, ie, it is determined by the following formula: 
(baseline SALT – post-baseline SALT)/baseline SALT x 100% = % change from baseline. 
Positive percentage change from baseline will denote improvement. For example: 75% hair 
loss at baseline (SALT score = 75), 50% hair loss at a post-baseline visit (SALT score = 50), 
the percent change from baseline = (75 - 50) / 75 x 100% = 33% regrowth. 
The key secondary endpoint for this study is the proportion of subjects achieving a 
30% improvement in SALT (SALT 30) at Week 24. A subject with a 30% improvement in 
SALT is one whose percent change from baseline is greater than or equal to 30 (SALT 30
= 1 if percent change from baseline 30, SALT 30 = 0 otherwise).  In addition to calculating 
SALT 30 at Week 24, SALT 30 will be calculated at all intermediate time points as well.
The proportion of subjects achieving a 50%, 75%, and 100% improvement in SALT (SALT 
50, SALT 75, and SALT 100) at all time points will be calculated in a similar manner to 
SALT 30.  For example, a subject will meet the SALT 50 definition if the percent change 
from baseline is greater than or equal to 50 (SALT 50 = 1 if percent change from baseline 
50, SALT 50=0 otherwise).
In addition to the change from baseline in SALT as described in the primary analysis, all 
intermediate timepoints will be used as secondary endpoints.  
Furthermore, it is believed by investigators that 90% improvement (SALT 90) is the same as
achieving remission, and therefore, SALT 90 at all timepoints may be summarized.   
The clinical evaluator of AA will perform an assessment of the overall improvement of AA 
and assign an IGA score and category as described in the table below. This takes into 
account extent and density of regrowth by the SALT scoring system. 


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 24
For determination IGA, the percent change from baseline in SALT score would be 
determined at each follow-up visit.
The IGA should be permitted to score 0 (no change or further loss) at baseline.
The IGA scores are defined as below.
Table 2.
IGA Score
Score
Description
0
No change or further loss
1
1-24% regrowth
2
25-49% regrowth
3
50-74% regrowth
4
75-99% regrowth
5
100% regrowth
3.3. Exploratory Efficacy Endpoint(s)
The eyelash assessment scale ranges from 0 (none) to 3 (normal) and corresponds to frontal 
and superior eyelash views. This assessment will be done at all study visits. Proportion of 
responders achieving at least 1 grade improvement in eyelash assessment scale at the 
scheduled timepoints in the study will be assessed for patients with eyelash involvement at 
baseline. The analysis will also be conducted with all patients in the full analysis set. 
Baseline will be the last measurement prior to randomization. The scores are as defined 
below.
The rating scale ranges from 0 (none) to 3 (normal) for eyelash assessment.  
Table 3.
Eyelash Assessment Scale
Score
Description
0
None
1
Minimal
2
Moderate
3
Normal
The eyebrow assessment scale ranges from 0 (none) to 3 (normal). The eyebrow assessment 
scale will be evaluated in all subjects. This assessment will be done at all study visits.  
Proportion of responders achieving at least 1 grade improvement in eyebrow assessment 
scale at the scheduled timepoints in the study will be assessed for patients with eyebrow
involvement at baseline. The analysis will also be conducted with all patients in the full 
analysis set. Baseline will be the last measurement prior to randomization.  The scores are as 
defined below. The rating scale ranges from 0 (none) to 3 (normal) for eyebrow assessment.  


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 25
Table 4.
Eyebrow Assessment Scale
Score
Description
0
None
1
Minimal
2
Moderate
3
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 26
 
 
 
 
 
3.5. Baseline Variables
Demographic and medical history will be collected at baseline.  Complete AA disease history 
includes collection of details of AA at Screening: background, AA history, AA diagnosis, 
pattern of scalp hair loss, body hair loss, nail involvement, the use of topical treatments, 
systemic treatments and other treatments for AA. Medical history, in addition to AA history, 
including history of drug, alcohol, tobacco use, skin rash, skin infection, and any dermal 
abnormalities that may predispose to infection will be collected at Screening. Smoking status 
and average weekly alcohol consumption (units/week) will also be collected.
3.6. Safety Endpoints
Safety will be assessed by the spontaneous reporting of AEs, physical examinations and 
clinical laboratory results in all subjects who receive at least one dose of the investigational 
product. Unscheduled safety assessments may be performed at any time during the study to 
assess any perceived safety concerns.
3.6.1. Adverse Events
An adverse event is considered treatment emergent relative to a given treatment if:
•
the event occurs for the first time during the effective duration of treatment and was 
not seen prior to the start of treatment (for example, during the baseline or run-in 
period), or
•
the event was seen prior to the start of treatment but increased in severity during 
treatment.
A 3-tier approach will be used to summarize AEs. Under this approach, AEs are classified
into 1 of 3 tiers. Different analyses will be performed for different tiers (See 
Section 6.1.6.1). 
Tier-1 events: These are pre-specified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan.
Tier-2 events: These are events that are not tier-1 but are “common”.  A MedDRA PT is 
defined as a tier-2 event if there are at least 4 in any treatment group.
Tier-3 events: These are events that are neither tier-1 nor tier-2 events.
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Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 27
3.6.2. Laboratory Data
The following laboratory tests (Table 5) will be performed at time points identified in the 
Schedule of Activities. Baseline will be the last measurement prior to receiving study 
treatment (Day 1). Unscheduled clinical labs may be obtained at any time during the study to 
assess any perceived safety concerns at the investigator’s discretion.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 28
Table 5.
Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Reticulocyte count
Platelet count
WBC count with differential
Total neutrophils (%, Abs)
Eosinophils (%, Abs)
Monocytes (%, Abs)
Basophils (%, Abs)
Lymphocytes (%, Abs)
BUN and Creatinine
Cystatin Ch
Creatine Phosphokinase
Glucose 
Na+, K+, Cl- ,Ca++
Total CO2 (Bicarbonate)
AST, ALT
Total Indirect & Direct Bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Fasting lipid Profile Panel f:
Total cholesterol
LDL 
HDL
Triglycerides
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Microscopy and/or 
cultured
HIVa
HBsAga
HBcAba
HepB reflex (HbsABa), if 
applicable
HCVAba
Serum pregnancy test a, c
Urine pregnancy test c
FSHa, g
QFT-G or other IGRA, or 
PPDa,e
EBV, CMV, HSV1, HSV2, 
VZV
 
 
 
Skin swab for herpetiform 
rashi
Skin swab for potential 
drug-related rashj
a
At Screening only.
b
HepB reflex testing only if HBsAg negative but HBcAb positive at Screening. 
c
Pregnancy tests (serum/urine) for females of childbearing potential.  Serum pregnancy test must be 
performed at Screening.
d
Only if urine analysis is positive for blood, protein, nitrites, or leukocyte esterase.
e
PPD results should be read within 48 to 72 hours.
f
Fasting lipid Profile Panel requires at least an 8 hour fast.  Lipid profile panel will be completed at Day 1, 
Week 8, Week 24, Week 28, and ET (if applicable), and will include total cholesterol, LDL, HDL, and 
triglycerides. 
g
Females of non-child bearing potential.
h
Cystatin C will be measured at baseline and EOT as well as the reflex testing if the serum creatinine is 
elevated above the ULN as specified in Section 7.3.7.2 of the protocol. 
i
In case of a herpetiform rash (eg, suspected herpes zoster and herpes simplex) Section 7.3.7.1.1 of the 
protocol.
j
In case of a potential drug-related rash as specified in Section 7.3.7.1.2 of the protocol.
k
At Screening, Week 28, and in case of CK > 3x ULN.
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Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 29
3.6.3. Vital Signs
Vital signs (blood pressure, pulse, respiratory rates and temperature) will be measured after 
5 minutes of rest as indicated in the Schedule of Activities. Baseline will be the last 
measurement prior to receiving study treatment.
3.6.4. Electrocardiograms
Single 12-lead ECGs should be collected at times specified in the Schedule of Activities.
The baseline ECG values (collected on Day 1) will serve as each subject’s baseline values.
To ensure safety of the subjects, 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.
Only categorical summaries of the ECG data will be provided.
4. ANALYSIS SETS
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in
each analysis population prior to and releasing the database and classifications will be 
documented per standard operating procedures.
4.1. Full Analysis Set
The full analysis set (FAS) consists of all randomized subjects, assigned to the randomized 
treatment regardless of what treatment, if any, was received.  The full analysis set is the 
primary patient population for the primary endpoints.  A randomized but not treated subject 
will be reported under their randomized treatment group for the full analysis set.
4.2. Safety Analysis Set
The safety analysis set consists of all subjects who receive at least one dose of study 
medication.  Subjects are classified according to actual study treatment received. The safety 
analysis set is the primary population for treatment administration/compliance and safety. A 
randomized but not treated subject will be excluded from the safety analyses.  A treated but 
not randomized subject will be reported under the treatment actually received. 
4.3. Other Analysis Sets
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06651600 or PF-06700841 and in whom at least one concentration value is 
reported.
5. GENERAL METHODOLOGY AND CONVENTIONS
An interim analysis will be performed when Week 12 data has been accumulated for 
approximately 66 subjects initially randomized.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 30
After the initial Treatment Period (Week 0-24) is finished 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 can be generated. The 
subjects, investigators, and site personnel will continue to be blinded to randomized study 
treatments throughout the remainder of the study until the protocol amendment 4 is 
implemented at which point the sponsor, investigators and site personnel will become 
unblinded to the study treatment (study subjects will be blinded for the duration of the 
Single-Blind Extension Period). The sponsor, investigators, site personnel, and study 
subjects will all be unblinded during the Cross-Over Open Label Extension Period.
After the protocol amendment 4 is implemented, an interim CSR will be developed to report 
the results of the initial 24-week Treatment Period.
The database will be officially released after last subject last visit occurs. The final analysis 
will be then conducted and the final CSR will be issued.
The decision rules for the primary analyses of the 24-week Treatment Period are described in 
the next section.
5.1. Hypotheses and Decision Rules
The null hypothesis to be tested is that the difference between PF-06700841 or PF-06651600 
and placebo is less than or equal to 0 vs the alternative hypothesis of the difference between 
PF-06700841 or PF-06651600 and placebo is greater than 0. Using a between-group 
comparison at Week 24, for PF-06700841 vs placebo and PF-06651600 vs placebo, the 
treatment will be considered superior to placebo if the lower bound of the 
97.5% (95% adjusted for two comparisons) one-sided confidence interval is greater than 0.
Because multiple comparisons are being made for the comparison between PF-06700841 and 
placebo and PF-06651600 and placebo, the Hochberg procedure will be used to adjust for 
multiple comparisons.  To apply the test, the treatment with the larger unadjusted p-value 
will be tested first.  If it is less than 0.05 then both treatment comparisons will be considered 
significant.  If the larger p-value is greater than 0.05, the smaller p-value will still be 
considered to be significant if it is less than 0.025.  Otherwise, neither value will be 
considered significant.
Adjustments for multiple comparisons will only be made for the primary endpoint at the 
Week 24 time point.  All other p-values reported will be considered descriptive.
5.2. General Methods 
5.2.1. Analyses for Binary Data
The frequency and percentages for all binary data will be presented.  Longitudinal binary 
data will be analyzed by a generalized linear mixed model, with fixed factors of treatment, 
visit, treatment by visit, baseline SALT score, baseline SALT score by treatment (if 
possible), and a random subject effect. P-values and inference for relative risks between 
treatments will be provided based on the link function of logit. A delta method will be used 
to derive point estimates and confidence intervals of relative risks, which is described in


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 31
Appendix 3. If the GLMM model does not converge, the estimates using Chan and Zhang’s 
exact method based on Non-Responder Imputation (NRI) will be presented.
Ordinal endpoints transformed as responder rates 
 
 will be analyzed using the method aforementioned for binary data.
Descriptive summaries for the ordinal endpoints will be presented with proportions of 
subjects in each category. 
5.2.2. Analyses for Continuous Data
A linear mixed-effect repeated measures model with fixed effects for treatment, time (visit), 
treatment by time, baseline SALT score, baseline SALT score by treatment, and a random 
effect for subject, will be used to analyze the change from baseline.
 
 The estimation method used will be
restricted maximum likelihood. Due to the unknown nature of the longitudinal data, different
covariance structures among repeated measures will be examined based on model diagnostics 
starting with the unstructured variance-covariance model. Using this model, 97.5% upper 
confidence bound (ie. 95% two-sided confidence interval) comparing the mean change from 
baseline for PF-06700841 vs. placebo and PF-06651600 vs placebo will be computed (for the 
primary endpoint). Sensitivity analysis for the primary endpoint will be completed using 
multiple imputation (MI) methods as described in Section 5.3. Another sensitivity analysis
for the primary endpoint will be a linear mixed effect model (for longitudinal data) regarding 
time as a continuous variable based on the observed data. 
 
 
 
5.3. Methods to Manage Missing Data
Multiple imputation (MI) will be used as a sensitivity analysis for the primary endpoint. The 
MI will impute the SALT score at least 100 times using the propensity score method for 
monotone missing pattern and the covariates of treatment, time, baseline SALT score, and 
duration since onset of current episode (if possible). Once the SALT score has been imputed, 
the analysis variable using the imputed SALT variable will be calculated.
Non-Responder Imputation (NRI) will be used for the binary endpoints  when Chan and 
Zhang’s exact method is performed, in which missing value will be imputed as 
Non-Responders. 
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Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 32
6. ANALYSES AND SUMMARIES
The placebo group for PF-06651600 and the placebo group for PF-06700841 will be 
combined for all analyses unless otherwise noted.
6.1. Analyses and Summaries During the Treatment Period
6.1.1. Primary Endpoint(s)
6.1.1.1. Change from Baseline for SALT score
6.1.1.1.1. Primary Analysis
Endpoint: Change from baseline in SALT

Analysis time points: Week 24 (primary) and all intermediate scheduled timepoints in 
the protocol.

Analysis population: FAS.

Analysis methodology: Change from baseline will be analyzed using a longitudinal
model (specified in Section 5.2.2).  
Reporting results:

Raw data: n, mean, standard deviation, median, minimum and maximum at baseline 
and post-baseline visits will be presented for each treatment arm;

Change from baseline: n, mean, standard deviation, median, minimum and maximum 
will be presented for each treatment arm. The LS means, 95% 2-sided confidence 
interval for the LS means, difference between the LS means for each pair of treatment 
groups and the corresponding 95% 2-sided confidence interval will be presented.  
Figures:

LS mean change from baseline by visit;

Placebo adjusted LS means and 95% 2-sided confidence interval at Week 24;

Placebo adjusted LS means and 90% 2-sided confidence interval will also be 
presented for all other intermediate time points to reflect trend over time.
6.1.1.1.2. Sensitivity/Robustness Analyses 
To support the interpretation of the primary analysis the following analyses will be 
performed:  
Endpoints: 

Change from baseline in SALT using multiple imputation for missing data;

Change from baseline in SALT without imputation.


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Analysis time points: Week 24 and all intermediate scheduled timepoints in the protocol.
Analysis population: FAS.
Analysis methodology: 

Change from baseline based on multiple imputation will be analyzed using a 
longitudinal model (specified in Section 5.2.2) in which visit is regarded as 
categorical variable;

Change from baseline without imputation will be analyzed as longitudinal data with
visit regarded as a continuous variable to explore whether time on treatment has
linear relationship with hair growth and consequently examine the treatment
difference.
Reporting results:

Change from baseline: n, LS means, 90% 2-sided confidence interval for the LS 
means, difference between the LS means for each pair of treatment groups and the 
corresponding 90% 2-sided confidence interval will be presented.  
Figures:

LS mean change from baseline by visit;

Placebo adjusted LS means and 90% 2-sided confidence interval at Week 24 and all 
intermediate scheduled time points in the protocol.
6.1.2. Secondary Endpoint(s)
6.1.2.1. SALT 30
Endpoint: SALT 30

Analysis time points: Week 24 (primary) and all intermediate scheduled timepoints in 
the protocol;

Analysis population: FAS;

Analysis methodology: proportion of subjects achieving a 30% improvement in 
SALT will be analyzed using a repeated measures GLMM model.  If the GLMM 
model does not converge the estimates using exact method will be presented. (see
Section 5.2.1).
Reporting results:

Raw data: The number and percentage of subjects meeting SALT 30 will be 
presented by visit;

Risk differences: The risk differences from placebo and the 90% 2-sided confidence 
interval for risk difference will be presented.


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Figures:

Plot of the proportion of subjects meeting SALT 30 with 90% 2-sided CI over time;

Plot of risk differences (compared to placebo) with 90% 2-sided CI by treatment 
group over time.
6.1.2.2. Change from Baseline in Investigator Global Assessment (IGA)
Endpoint: IGA

Analysis time points: All post-baseline visits during Treatment Period;

Analysis population: FAS;

Analysis methodology: number and percentage of subjects in each category will be 
presented (see Section 5.2.1).
Reporting results:

The number and percentage of subjects in each category will be presented by visit and 
by treatment.
Figures:

Vertical bar chart of the percentage of subjects in each category will be presented by 
visit and by treatment.
6.1.2.3. SALT 50, SALT 75, SALT 90 and SALT 100
The analyses will be identical to the analysis used for SALT 30 (Section 6.1.2.1).
6.1.2.4. Percentage change in SALT
Endpoint: Percentage change from baseline in SALT

Analysis time points: All visits during Treatment Period;

Analysis population: FAS;

Analysis methodology: Percentage change from baseline will be analyzed using a 
longitudinal model (specified in Section 5.2.2).  
Reporting results:

Raw data: n, mean, standard deviation, median, minimum and maximum at baseline 
and post-baseline visits will be presented for each treatment arm.


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•
Percentage change from baseline: n, mean, standard deviation, median, minimum and 
maximum will be presented for each treatment arm. The LS means, 90% 2-sided 
confidence interval for the LS means, difference between the LS means for each pair 
of treatment groups and the corresponding 90% 2-sided confidence interval will be 
presented.  
Figures:
•
LS mean percentage change from baseline in SALT by visit;
•
Placebo adjusted LS means and 90% 2-sided confidence interval at Week 24 and all 
intermediate scheduled timepoints in the protocol.
6.1.3. Other Endpoint(s)
 
 
 
 
 
 
 
 
  
 
 
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6.1.4. Subset Analyses 
Summary statistics and statistical analyses for the primary and secondary endpoints may be 
presented for AT/AU subjects.
6.1.5. Baseline and Other Summaries and Analyses
6.1.5.1. Baseline Summaries
Demographics and AA medical history variables as defined in Section 3.5 will be 
summarized by treatment group.
6.1.5.2. Study Conduct and Subject Disposition
Subject evaluation groups will show end of study subject disposition and will show which 
subjects were analyzed in the full analysis set, and as well as for safety.  Frequency counts 
will be supplied for subject discontinuations by treatment.
Data will be reported in accordance with reporting standards.
6.1.5.3. Study Treatment Exposure and Compliance
Compliance will be calculated for each subject using the formula:
Compliance = (# tablets actually administrated / # tablets planned) * 100.
A summary of compliance and the number of doses received as well as the median total dose 
by visit and treatment group will be provided.  This will be done for both the induction and 
maintenance phases as well as overall.  For these summaries, the placebo groups will be 
treated as separate groups since the dosing was different depending on which arm the subject 
was assigned to.
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6.1.5.4. Concomitant Medications and Non-Drug Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
6.1.6. Safety Summaries and Analyses
6.1.6.1. 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 adverse event or a group of 
adverse events. Except for select events in unique situations, studies do not employ formal 
adjudication procedures for the purpose of event classification. 
 
 
 
The Treatment emergent adverse events (TEAEs) by system organ class and preferred term 
will be generated for the induction phase,  maintenance phase, and Treatment Period, 
respectively, for both all causality and treatment-related AEs. The Serious TEAEs (both all 
causality and treatment-related) by system organ class and preferred term may also be 
generated for induction phase, maintenance phase, and Treatment Period, respectively, as
needed.
Nominal p-values (Tier 1 events only) and 90% confidence intervals (Tier 1 and Tier 2 
events) will be provided for between treatment differences in the percentage of patients with 
events. Reporting p-values and confidence intervals will follow Pfizer standards.
6.1.6.2. 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 
liver function tests (LFTs). 
The following laboratory abnormalities require re-testing within 1 week until resolution or 
agreement with Pfizer.
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Table 6.
Laboratory Re-Testing Criteria
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil Count
<2000/mm3 (2.0 x109/L)
Hemoglobin
<9.0 g/dL
Platelet count
<100,000/mm3 (100 x109/L)
Lymphocytes
<600/mm3; <0.6x109/L
Chemistry
CK
>3xULN (This also triggers urine myoglobin.)
Laboratory meeting the following criteria will be summarized by number and percent.
Table 7.
Laboratory Abnormality Criteria
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil Count
<1000/mm3; <1.0 x109/L
Hemoglobin
<8.0 g/dL; <4.96 mmol/L; <80 g/L
Platelet count
<75,000/mm3; <75.0x109/L
Lymphocytes
<500/mm3; <0.5x109/L
Chemistry
AST
>2.5x ULN
ALT
>2.5x ULN
Total bilirubin
>1.5x ULN
CK
>10x ULN
6.1.6.3. Vital Signs
Absolute values and changes from baseline in systolic and diastolic blood pressure, 
respiratory rate, pulse rate and temperature will be summarized by treatment and time 
post-dose, according to sponsor reporting standards.  Baseline is as defined in Section 3.6.3.
6.1.6.4. Electrocardiogram
Categorical summary tables will be summarized by treatment and time post-dose using 
sponsor reporting standards. Baseline is as defined in Section 3.6.4. A listing of ECG 
comments on findings and normal/abnormal results will be provided. 


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6.1.6.5. Physical Examination
All physical exam data will be provided in the listings.
6.2. Analyses and Summaries During the Single-Blind Extension Period
At Week 24, subjects will be evaluated for eligibility of entering the Single-Blind Extension 
Period and be assigned to receive either Placebo or Active treatments at Week 28. Post 
Week 28, subjects who started with placebo at Week 28 may be re-treated with active 
treatment if pre-specified criteria are met. See details in Appendix 4. Below lists the routes 
subjects may go through. 
Initial 24-Week Treatment Period
→ Single-Blind Extension Period →
(may go to) Active Treatment
Description
Placebo →PF-06651600
Placebo Non-responders. The subjects initially 
treated with placebo in the Treatment Period will 
be assigned to the active treatment in the 
Single-Blind Extension Period.
Placebo →PF-06700841
PF-06651600 →PF-06651600
Active Non-responders. The subjects initially 
treated with active treatment in the Treatment
Period will be continued with active treatment in 
the Single-Blind Extension Period if Week 24 
SALT 30 = 0.
PF-06700841 →PF-06700841
PF-06651600 →Placebo 
Responders. The subjects initially treated with 
active treatment in the Treatment Period will be 
assigned to Placebo in the Single-Blind 
Extension Period if SALT 30 =1. 
PF-06700841 →Placebo
PF-06651600 →Placebo →
PF-06651600
Responders with Retreatment. The subjects 
initially treated with active treatment in the 
Treatment Period will be assigned to Placebo in 
the Single-Blind Extension Period if SALT 30 =
0, and be re-treated with active treatment post 
Week 28 if PCB (Week 24) – PCB (post Week 
24) >30. 
PF-06700841 →Placebo →
PF-06700841
In general, for efficacy endpoints, analyses and summaries will be presented by visit and 
above listed group. 
For safety endpoints and pharmacodynamics endpoints, analyses and summaries will be 
presented by visit and treatment; presentations will be shown separately for the Single-Blind 
Extension Period Week 28 – Week 52 visits (when all subjects are first treated with either an 
active drug or placebo in the Single-Blind Extension Period) and Active Treatment Visits 
(when Responders are re-retreated with active drugs). Baseline will be the same as baseline 
in Treatment Period.


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6.2.1. Primary Endpoints (Safety)
A set of safety summary tables will be produced to evaluate potential risks associated with 
the safety and tolerability of administering the study medication. All clinical AEs, SAEs, 
on-treatment AEs, 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, standard deviation etc.
Change from baseline and percent change from baseline on selected safety endpoints may be 
additionally 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 6.1.6 (except for the 3-tier analysis which does not need to be conducted in the 
Single-Blind Extension Period) for the analysis during Treatment Period.
6.2.2. Exploratory Efficacy Analysis
6.2.2.1. Continuous Endpoints
Endpoints: 

Change from baseline in SALT;

Change from baseline in Pruritus Numerical Rating Scale;

Change from baseline in AASIS.
Analysis time points: All time points during the complete study including Treatment and 
Single-Blind Extension Period.
Analysis population: All Placebo Non-responders, Active Non-responders, and Responders 
with Retreatment who have received at least one dose of planned investigational product in 
the Single-Blind Extension Period.
Analysis methodology:

Summary statistics will be provided;

For the Single-Blind Extension Period, change from baseline will be analyzed using a 
MMRM model (specified in Section 5.2.2) to compare Non-responders and 
Responders with Retreatment.
Note that, in the above descriptive summary and MMRM model, subjects will be broken 
down by the following 
4 reporting groups:
Placebo →PF-06651600 and PF-06651600 →PF-06651600;
Placebo →PF-06700841 and PF-06700841 →PF-06700841;


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PF-06651600 →Placebo →PF-06651600;
PF-06700841 →Placebo →PF-06700841, and 
visits:
Week 30/ AT Week 2, Week 32/ AT Week 4, Week 34/ AT Week 6, Week 36/ AT Week 8, 
Week 40/ AT Week 12, Week 44/ AT Week 16, Week 48/ AT Week 20, Week 52/ AT 
Week 24.
To examine the initial placebo subjects responses after treated with active drugs when 
entering Single-Blind Extension Period, a MMRM model for Placebo Non-responders (only 
subjects eligible and entered the Single-Blind Extension Period) will be performed. 
Placebo →PF-06651600 
(Single-Blind Extension Period: Week 28 –
Week 52)
vs
Placebo
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06700841 
(Single-Blind Extension Period: Week 28 –
Week 52)
Note that, subjects will be broken down by the following:
4 reporting groups:
Placebo (randomized to pair with PF-06651600);
Placebo (randomized to pair with PF-06700841);
Placebo →PF-06651600;
Placebo →PF-06700841, and 
visits:
Week 2/ Week 30, Week 4/ Week 32, AT Week 6/ Week 34, AT Week 8/ Week 36, 
Week 12/ Week 40, Week 16/ Week 44, Week 20/ Week 48, Week 24/ Week 52.
Reporting results: 

Raw data: n, mean, standard deviation, median, minimum and maximum at baseline 
and post-baseline visits will be presented;


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
Change from baseline: n, mean, standard deviation, median, minimum and maximum 
will be presented. The LS means, 90% 2-sided confidence interval for the LS means;
difference between the LS means for each pair of reporting groups and the 
corresponding 90% 2-sided confidence interval will also be presented.
Figures:

LS mean change from baseline and corresponding 90% 2-sided confidence interval 
by visit and by reporting group.  

LS mean of treatment difference in change from baseline and corresponding 
90% 2-sided confidence interval by visit and reporting group for the Non-responders 
and Responders with Retreatment.
Note that Non-responders and Responders will be both plotted in the figures above 
and the Active Treatment (AT) visits will be aligned with Week 28 – Week 52 to 
compare the trajectory of 24-week response in the Single-Blind Extension Period, ie,
Week 30/AT Week 2, …, Week 52/AT Week 24.

LS mean of treatment difference in change from baseline and corresponding 90% 
2-sided confidence interval by visit and reporting group for the initial placebo treated 
subjects (only subjects eligible and entered the Single-Blind Extension Period).
Note that the timepoints will be aligned as Week 2/Week 30, …, Week 24/Week 52
to indicate subjects’ visits in Treatment Period and their visits in the Single-Blind 
Extension Period.

In addition, the active vs placebo comparisons in both the Treatment Period and the 
Single-Blind Extension Period will be presented in the same figure. That is, the LS 
mean change from baseline and the LS mean of treatment difference of the following
comparisons will be plotted.
PF-06651600 
(Treatment Period: Day 1 – Week 24)
vs
Placebo 
(Treatment Period: Day 1 – Week 24)
PF-06700841
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06651600 
(Single-Blind Extension Period: Week 
28 – Week 52)
vs
Placebo
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06700841 
(Single-Blind Extension Period: Week 
28 – Week 52)
Note that the Single-Blind Extension Period visits will be aligned with the Treatment Period 
visits to compare the trajectory of 24-week response, ie, Week 2/ Week 30, …, Week 
24/Week 52.


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6.2.2.2. Binary Endpoints
Endpoints: 

SALT 30, SALT 50, SALT 75, SALT 90 and SALT 100;

Proportion with one grade improvement in eyelash assessment scale;

Proportion with one grade improvement in eyebrow assessment scale.
The following descriptions use SALT 30 as an example. The analyses for all binary 
endpoints are identical.
Analysis time points: All time points during the complete study including the Treatment and 
Single-Blind Extension Periods.
Analysis population: All Placebo Non-responders, Active Non-responders, and Responders 
with Retreatment who have received at least one dose of planned investigational product in 
the Single-Blind Extension Period.
Analysis methodology:

The number and percentage achieving a 30% improvement in SALT will be provided.

For the Single-Blind Extension Period, proportion of subjects achieving a 
30% improvement in SALT will be analyzed using a repeated measures GLMM 
model (specified in Section 5.2.1) for Non-responders and Responders with 
Retreatment.  If the GLMM model does not converge, only the estimates using exact 
method will be presented.
Note that, in the above descriptive summary and analyses, subjects will be broken 
down by the following 
4 reporting groups:
Placebo → PF-06651600 and PF-06651600 → PF-06651600;
Placebo → PF-06700841 and PF-06700841 → PF-06700841;
PF-06651600 → Placebo → PF-06651600;
PF-06700841 → Placebo → PF-06700841, and 
visits:
Week 30/ AT Week 2, Week 32/ AT Week 4, Week 34/ AT Week 6, Week 36/ AT 
Week 8, Week 40/ AT Week 12, Week 44/ AT Week 16, Week 48/ AT Week 20, 
Week 52/ AT Week 24.

To examine the initial placebo subjects responses after treated with active drugs when 
entering the Single-Blind Extension Period, a GLMM model for Placebo 
Non-responders (only subjects eligible and entered the Single-Blind Extension Period) 
will be performed.


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Placebo →PF-06651600 
(Single-Blind Extension Period: Week 
28 – Week 52)
vs
Placebo
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06700841 
(Single-Blind Extension Period: Week 
28 – Week 52)
Note that, subjects will be broken down by the following:
4 reporting groups:
Placebo (randomized to pair with PF-06651600);
Placebo (randomized to pair with PF-06700841);
Placebo →PF-06651600;
Placebo →PF-06700841, and 
visits:
Week 2/ Week 30, Week 4/ Week 32, AT Week 6/ Week 34, AT Week 8/ Week 36, 
Week 12/ Week 40, Week 16/ Week 44, Week 20/ Week 48, Week 24/ Week 52. If 
the GLMM model does not converge, the estimates using exact method will be 
performed.
Reporting results: 

Raw data: The number and percentage of subjects meeting SALT 30 will be 
presented;

Risk differences: The risk differences and the 90% 2-sided confidence interval for 
risk difference will be presented.  
Figures:

Plot of the proportion of subjects meeting SALT 30 in the Single-Blind Extension 
Period by visit and by reporting group;

Risk difference between each pair of reporting groups with corresponding 
90% 2-sided confidence interval will be plotted for the Non-responders and 
Responders with Retreatment;
Note that Non-responders and Responders will be both plotted in the figures above
and the Active Treatment (AT) visits will be aligned with Week 28 – Week 52 to 
compare the trajectory of 24-week response in the Single-Blind Extension Period, ie,
Week 30/AT Week 2, …, Week 52/AT Week 24;


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•
Risk difference between each pair of reporting groups with corresponding 
90% 2-sided confidence interval will be plotted for the initial placebo treated subjects 
(only subjects eligible and entered the Single-Blind Extension Period).
Note that the timepoints will be aligned as Week 2/Week 30, …, Week 24/Week 52
to indicate subjects’ visits in Treatment Period and their visits in the Single-Blind 
Extension Period.
•
In addition, the active vs placebo comparisons in both the Treatment Period and the 
Single-Blind Extension Period will be presented in the same figure. That is, the risk 
differences of the following comparisons will be plotted.
PF-06651600 
(Treatment Period: Day 1 – Week 24)
vs
Placebo 
(Treatment Period: Day 1 – Week 24)
PF-06700841
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06651600 
(Single-Blind Extension Period: Week 
28 – Week 52)
vs
Placebo
(Treatment Period: Day 1 – Week 24)
Placebo →PF-06700841 
(Single-Blind Extension Period: Week 
28 – Week 52)
Note that the Single-Blind Extension Period visits will be aligned with the Treatment Period 
visits to compare the trajectory of 24-week response, ie, Day 1/Week 28, …, Week 24/Week 
52.
 
 
 
 
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6.2.2.4. Placebo Treatment Duration: Time to Event (Retreatment) and Change from 
Baseline for Single-Blind Extension in SALT Endpoints 
Endpoint: 
•
Time to achieve the pre-specified retreatment criteria (see Appendix 4) during the 
Single-Blind Extension Period;
 
Analysis time points: All visits when subjects are treated with placebo during the 
Single-Blind Extension Period.
Analysis population: All Responders including Responders with and without retreatment .
Analysis methodology: 
•
Kaplan-Meier analysis will be performed for time to reach the  retreatment criteria
(see Appendix 4). 
 
 
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Reporting results:
•
The Kaplan-Meier estimator will be provided for each reporting group;
•
The raw number and percentage of subjects achieving pre-specified retreatment 
criteria will be presented over time by reporting group;
 
Figures:
•
The Kaplan-Meier estimator will be plotted for each treatment group;
 
 
 
  
 
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6.3. Analyses and Summaries During the Cross-over Open-Label Extension Period
6.3.1. Primary Endpoints (Safety)
The analyses for safety endpoints for the Cross-over Open Label Extension Period will be the 
same as those for the Single-Blind Extension Period (see Section 6.2.1).  Descriptive 
summaries will be presented by treatment groups. The 3-tier analysis for adverse events will 
not be performed.
For change from baseline and percent change from baseline on selected safety endpoints, 
baseline is defined as the last measurement at the end of the Single-Blind 
Withdrawal/Retreatment Extension Period (ie, Week 52 visit).
 
 
 
 
 
 
 
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6.4. Interim Clinical Study Report
After the last subject last visit for the initial 24-week Double-Blind Treatment Period is 
achieved, data will be cleaned, a snapshot of the database will be created, and all the efficacy 
and safety data from the 24-week Treatment Period will be summarized in an interim clinical 
study report (CSR) and published. The analyses and summaries for the Double-Blind 
Treatment Period described in Section 6.1 will be performed. The interim CSR may be 
shared with the principal investigator (PI) when it is available.
7. INTERIM ANALYSES
7.1. Introduction
A separate interim analysis plan for this protocol will include an interim analysis using SALT 
total for both 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 will 
be performed when approximately 50% of subjects have completed the Week 12 visit or 
discontinued from the study.
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7.2. Interim Analyses and Summaries
The objective of the interim analysis is to determine if there is evidence of lack of 
differentiation (“futility”) for the active treatments compared to placebo. The interim 
analysis is based on predicted power conducted on a total of approximately 66 subjects who 
have completed the Week 12 visit or discontinued from the study. A non-informative prior 
will be used for the interim analysis. The decision at the end of the study is being at least 
95% confident that active treatment will be superior to placebo (DC1). 
The study will be stopped for futility for that active treatment arm if predictive power of
meeting DC1 at the end of study is <10% for that active arm. Due to the nature of the
analyses the overall Type 1 error for the study is maintained. If the futility condition is met
for both active arms, the study will be stopped at the interim point.
The interim analysis results will be used to facilitate internal decision-making. The results
will only be distributed to a select list of individuals involved in the internal decision-making
process in order to protect the integrity of the study. This list of individuals will be provided
in the interim analysis plan. The results of the interim analysis will not enable individuals
directly involved in running the study (such as investigators) to identify treatment
assignments for individual subjects still in the study. There are no prospective plans to stop
the study early for success as a result of the interim analyses. During the interim analysis, 
some members of the study team may be unblinded and replaced with blinded colleagues. 
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 follow up period of the study.  


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8. REFERRENCES
1.
Olsen, E. A. (2011). "Investigative guidelines for alopecia areata." Dermatologic 
Therapy 24(3): 311-319.
2.
B7931005 protocol amendment 3. August 02, 2017.


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9. APPENDICES 
Appendix 1. Summary of Efficacy Analyses
Appendix 1.1. Summary of Efficacy Analyses in the Treatment Period
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing Data
Imputation
Interpretation
Change from baseline 
in SALT at Week 24
and at intermediate 
time points
FAS
Summary 
statistics
None
None
Primary and 
Secondary
Change from baseline 
in SALT at Week 24 
and at intermediate 
time points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Primary and
Secondary
Change from baseline 
in SALT at Week 24
and at intermediate 
time points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
Multiple 
Imputation
Sensitivity
Change from baseline 
in SALT at Week 24 
and at intermediate 
time points
FAS
Linear mixed 
effect model 
for 
longitudinal 
data 
regarding 
visit as a 
continuous 
variable 
Treatment, Visit, 
Treatment* Visit, 
baseline SALT 
None
Sensitivity
SALT 30 at Week 24
and at intermediate 
time points
FAS
Summary 
statistics
None
None
Secondary
SALT 30 at Week 24
and at intermediate 
time points
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Secondary
SALT 30 at Week 24
and at intermediate 
time points
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
IGA
FAS
Summary 
statistics
None
None
Secondary
Percent Change from 
baseline in SALT at all 
FAS
Summary 
None
None
Secondary


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 55
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing Data
Imputation
Interpretation
time points
statistics
Percent Change from 
baseline in SALT at all 
time points
FAS
MMRM
None
None
Secondary
SALT 50 at all time 
points
FAS
Summary 
statistics
None
None
Secondary
SALT 50 at all time 
points
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Secondary
SALT 50 at all time 
points
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
SALT 75 at all time 
points
FAS
Summary 
statistics
None
None
Secondary
SALT 75 at all time 
points
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment  
None
Secondary
SALT 75 at all time 
points
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
SALT 90 at all time 
points
FAS
Summary 
statistics
None
None
Secondary
SALT 90 at all time 
points
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment  
None
Secondary
SALT 90 at all time 
points
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
SALT 100 at all time 
points
FAS
Summary 
statistics
None
None
Secondary
SALT 100 at all time 
points
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
None
Secondary


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 56
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing Data
Imputation
Interpretation
SALT*treatment  
SALT 100 at all time 
points
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
Eyelash assessment 
scale
FAS
Summary 
statistics
None
None
Exploratory
One grade 
improvement in 
Eyelash assessment 
FAS
GLMM
None
None
Exploratory
One grade 
improvement in 
Eyelash assessment 
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
Eyebrow assessment 
scale
FAS
Summary 
statistics
None
None
Exploratory
One grade 
improvement in 
Eyebrow assessment 
FAS
GLMM
None
None
Exploratory
One grade 
improvement in 
Eyebrow assessment 
FAS
Chan and 
Zhang’s exact 
test
None
Non-Respond
er Imputation
Secondary
AASIS
FAS
Summary 
statistics
None
None
Exploratory
Change from baseline 
in AASIS at all time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Exploratory
C-SSRS
FAS
Summary 
statistics
None
None
Exploratory
NRS
FAS
Summary 
statistics
None
None
Exploratory
Change from baseline 
in NRS at all time 
points
FAS
MMRM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Exploratory


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 57
Appendix 1.2. Summary of Efficacy Analyses in the Single-Blind Extension Period
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing Data
Imputation
Interpretation
Change from 
baseline in SALT, 
NRS, AASIS
FAS
Summary 
statistics
None
None
Exploratory
 
 
 
 
 
 
SALT 30, SALT 
50, SALT 75,
SALT 90,
SALT 100,
 
 
FAS
Summary 
statistics
None
None
Exploratory
SALT 30, SALT 
50, SALT 75, 
SALT 90,
SALT 100, 
 
FAS
GLMM
Treatment, Visit, 
Treatment* Visit, 
baseline SALT, 
baseline 
SALT*treatment 
None
Exploratory
SALT 30, SALT 
50, SALT 75, 
SALT 90,
SALT 100,
 
 
 
 
FAS
Chan and 
Zhang’s 
exact test
None
Non-Respond
er Imputation
Exploratory
 
 
Time to 
retreatment
FAS (all 
Responders 
at Week 
24)
Kaplan-Mei
er
None
Exploratory
CCI
CCI
CCI
CCI
CCI


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 58
Endpoint
Analysis 
Set
Statistical 
Method
Model
Missing Data
Imputation
Interpretation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 59
Appendix 2. Data Derivation Details
Appendix 2.1. Definition and Use of Visit Windows in Reporting the Initial Treatment 
Period
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 -35
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 36
Visit 5 (Day 43, Week 6)
Day 37
Day 50
Visit 6 (Day 57, Week 8)
Day 51
Day 71
Visit 7 (Day 85, Week 12)
Day 72
Day 99
Visit 8 (Day 113, Week 16)
Day 100
Day 127
Visit 9 (Day 141, Week 20)
Day 128
Day 155
Visit 10 (Day 169, Week 24)
Day 156
Day 176
Appendix 2.2. Definition and Use of Visit Windows in Reporting the Single-Blind 
Extension Period
Visit
Target Day
Start Day
End Day
Visit 11 (Week 28) /
Visit 20 (AT Day 1)
Week 28 Day 1/
AT Day 1
Visit 12 (Week 30) /
Visit 21 (AT Week 2)
Week 28 Day 1/
AT Day 1 + 14
Target Day -6
Target Day +7
Visit 13 (Week 32) /
Visit 22 (AT Week 4)
Week 28 Day 1/
AT Day 1 + 28
Target Day -6
Target Day +7


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 60
Visit 14 (Week 34) /
Visit 23 (AT Week 6)
Week 28 Day 1/
AT Day 1 + 42
Target Day -6
Target Day +7
Visit 15 (Week 36) /
Visit 24 (AT Week 8)
Week 28 Day 1/
AT Day 1 + 56
Target Day -6
Target Day +7
Visit 16 (Week 40) /
Visit 25 (AT Week 12)
Week 28 Day 1/
AT Day 1 + 84
Target Day -6
Target Day +7
Visit 17 (Week 44) /
Visit 26 (AT Week 16)
Week 28 Day 1/
AT Day 1 + 112
Target Day -6
Target Day +7
Visit 18 (Week 48) /
Visit 27 (AT Week 20)
Week 28 Day 1/
AT Day 1 + 140
Target Day -6
Target Day +7
Visit 19 (Week 52) /
Visit 28 (AT Week 24)
Week 28 Day 1/
AT Day 1 + 168
Target Day -6
Target Day +7
 
CCI


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 61
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; and using ilink option in GLIMMIX 
will generate the estimate for proportions. The variance of risk difference (proportion 
difference) cannot be directly obtained by GLIMMIX procedure using link=logit. This 
appendix describes how to obtain the estimate and the confidence interval (CI) for risk 
difference (proportion difference) by delta method.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 62


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 63
Appendix 4. Criteria for Treatment Assignment/Subject Retreatment during the 
Extension Periods
All subjects who complete the initial 24-week Treatment Period will be evaluated during the 
Drug Holiday #1 for potential entry into the Single-Blind Extension Period.  After the 
4-week Drug Holiday, subjects will enter the Extension Period providing none of the 
Exclusion criteria #9, #10, and #26 (see below) are met and the audiogram results does not 
preclude patient’s entry into the Single-Blind Extension Period. The non-responder criteria 
will be checked at Week 24 to determine if a subject should enter the segment for 
non-responder or the Withdrawal/Retreatment segment.  Subjects who meet Exclusion 
criteria #9, #10, or #26 will be directly entered into the Follow-up Period. Please note that all 
placebo patients in the Treatment Period who are eligible for the Single-Blind Extension 
Period will be assigned to active treatment.
All subjects who are assigned to receive active treatment (PF-06651600 or PF-06700841) 
directly and complete the segment for non-responder in Single-Blind Extension Period may 
be evaluated for potential entry into the Cross-Over Open Label Extension Period during the 
Drug Holiday #2.  Subjects will enter the Cross-Over Open Label Extension Period providing 
none of the Exclusion criteria #9, #10, and #26 are met and the audiogram result does not 
preclude patient’s entrance in the Cross-Over Open Label Extension Period as well as the 
non-responder criteria is met at Week 52. Subjects who complete the 
Withdrawal/Retreatment segment will go directly to the Follow-up Period and will not 
participate in the Cross-Over Open Label Extension Period.
Exclusion criteria #9, #10, #26
#9. 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; or in the opinion of the investigator or Pfizer
(or designee), the subject is inappropriate for entry into this study, or unwilling/unable to 
comply with Study Procedures and Lifestyle Requirements.
#10. Have current or recent history of clinically significant severe, progressive, or 
uncontrolled hearing loss or auditory disease.
#26. 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);

Hemoglobin <10.0 g/dL or hematocrit <30%; 

Platelet count below the lower limit of normal (LLN) at Screening;


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 64

Absolute lymphocyte count of <0.8 x 109 /L (<800/mm3); 

serum creatinine > upper limit of normal (ULN) or eGFR <80 ml/min/1.73m2 based 
on the age appropriate calculation;

enzymes aspartate transaminase (AST) or alanine transaminase (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;

CK >3 times the ULN and positive urine myoglobin;

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.
The Responder/Non-responder Criteria
-
During Drug Holiday # 1, SALT 30 at Week 24 will be calculated:  

Calculate % change from baseline: (SALT baseline – SALT Week 24)/SALT 
baseline X 100% 

If the % change from baseline 30 then SALT 30 = 1 or 0 otherwise

If the SALT 30 = 1 then the subject will be assigned to receive placebo at Week 
28 and enter the Withdrawal /Retreatment segment for responders in the 
Single-Blind Extension Period.  

If the SALT 30 = 0 then the subject will be assigned to receive active treatment at 
Week 28 and enter the segment for non-responders in the Single-Blind Extension 
Period.
-
During Drug Holiday # 2, SALT 30 at Week 52 will be calculated:  

Calculate % change from baseline: (SALT baseline – SALT Week 52)/SALT 
baseline X 100%;

If the % change from baseline ≥30 then SALT 30 = 1 or 0 otherwise;

If the SALT 30 = 0 then the subject is a non-responder and will enter Cross-Over 
Open Label Extension Period with the treatment alternative to that is used in the 
Single-Blind Extension Period;

If the SALT30 =1 then subject is a responder at Week 52 and will enter the 
Follow-up Period directly.


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 65
The Retreatment Criteria
In the Withdrawal/Retreatment segment of the Single-Blind Extension Period, the responders 
will be evaluated at each post Week 28 visit to determine if retreatment criteria met:
-
PCB (post Week 24): Calculate percent change from baseline as (SALT baseline –
SALT post week 24)/SALT baseline X 100%;
-
PCB (Week 24): Calculate percent change from baseline as (SALT baseline – SALT 
week 24)/SALT baseline X 100%;
-
If PCB (Week 24) – PCB (post Week 24) >30 then the subject will be re-assigned to 
receive active treatment;
-
If PCB (Week 24) – PCB (post Week 24) ≤30 then the subject will continue to 
receive placebo.  


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 66
Appendix 5. Severity of Alopecia Tool (SALT)
(Olsen 2011)1
SALT score= 0.18×score_left side + 0.18×score_right side + 0.4×score_top + 0.24×
score_back 
For Example:


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 67


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 68


Protocol B7931005 (PF-06651600; PF-06700841) 
Statistical Analysis Plan, Amendment 3
Page 69
CCI
CCI
CCI