Clinical trial NCT04517864
Conditions: Alopecia Areata
Keywords: alopecia totalis alopecia universalis hair loss alopecia JAK ritlecitinib PF-06651600 double-blind placebo-controlled phase 2a
Sponsor: Pfizer
Start date: 2020-09-15; Completion date: 2024-05-07
Enrollment: 71 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a global Phase 2a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of ritlecitinib in adults aged 18 to ≤50 years of age with ≥25% scalp hair loss due to Alopecia Areata (AA).

Detailed description:

Arms: arm 1: ritlecitinib 200 milligram (mg) once per day (QD) (four 50 mg tablets) for 4 weeks then ritlecitinib 50 mg tablet QD through month 24. At Month 9, participants assigned to this treatment arm will also receive 3 tablets of placebo for 4 weeks to maintain the blind with the other arm. After month 24, participants switch to 50 mg capsules, 1 QD, up to month 60. arm 2: matching comparator: placebo QD (4 tablets x 4 weeks then 1 tablet x 8 months) then ritlecitinib 200 mg QD (four 50 mg tablets) for 4 weeks then ritlecitinib 50 mg tablet QD through month 24. After month 24, participants switch to 50 mg capsules, 1 QD, up to month 60.
Interventions: intervention 1: PF-06651600 intervention 2: Placebo
Intervention descriptions: intervention 1: 50 mg tablet, dosed as 200 mg QD or 50 mg QD 50 mg capsule, dosed as 50 mg QD intervention 2: tablet, dosed as 4 tablets QD or 1 tablet QD

Protocol documents:
Prot_002.pdf: 
PF-06651600 
B7981037 
Final Protocol Amendment 2, 28 April 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
Protocol Title: A PHASE 2a, RANDOMIZED, DOUBLE-BLIND, PLACEBO- 
CONTROLLED STUDY INVESTIGATING THE SAFETY OF RITLECITINIB 
(PF-06651600) IN ADULT PARTICIPANTS WITH ALOPECIA AREATA 
Protocol Number: B7981037 
Study Intervention Number: PF-06651600 
Study Intervention Name: Ritlecitinib 
Study Phase: Phase 2a 
Short Title: PLACEBO-CONTROLLED SAFETY STUDY OF RITLECITINIB (PF- 
06651600) IN ADULTS WITH ALOPECIA AREATA 
Sponsor Name: Pfizer, Inc 
Legal Registered Address: 235 East 42nd Street, New York, NY 10017-5755, USA 
Regulatory Agency Identifier Number(s) 
Registry 
ID 
IND 
131503 
EudraCT 
2020-001509-21 
 
Approval Date: 28 April 2022 
 
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified. 


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Final Protocol Amendment 2, 28 April 2022 
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Protocol Amendment Summary of Changes Table 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis 
Updated with full study title 
This update was made to 
correct the omission in 
previous amendment. 
Section 1.1 Synopsis 
Section 1.2 Schema; 
Section 1.3.2.1 Treatment periods 1 
and 2 (TP1 and TP2): Day 1 
through Month 15E; 
Section 1.3.2.2 Treatment Period 3 
(TP3): Month 15E to Month 51E; 
Section 1.3.3. Early Termination 
and Follow-up; Section 4.1 Overall 
Design; 
Section 4.2 Scientific Rationale for 
Study Design; 
Section 4.3 Justification for Dose; 
Section 4.4 End of Study 
Definition; Section 6.1 Study 
Intervention; 
Section 8.2.13 Pregnancy Testing; 
Section 9.4.2 Efficacy Analysis; 
Section 9.4.3 Safety Analysis; 
Section 10.7.2 Discontinuation 
Section 10.9.3.1 Laboratory Testing 
(Usual Safety Assessments); 
Study extension for all 
participants to continue to 
receive open-label 50 mg 
PF-06651600 QD. 
Study updated to have 2 active 
treatment periods in addition to 
placebo-controlled period (TP1). 
Treatment from Month 9 to 
Month 15E is TP2. TP3 will be 
of variable length for individual 
participants; assuming a 
participant does not require 
discontinuation per protocol, a 
participant may continue to 
receive study intervention in 
TP3 for a maximum of an 
additional 36 months or until 
availability of commercial 
product in their country, or until 
the Sponsor terminates the study 
in that country, whichever 
occurs first. 
In order to allow study 
participants continued 
access to study 
intervention with 
collection of additional 
long-term safety and 
efficacy data, study 
duration is extended up 
to 60 months (or until 
availability of 
commercial product in 
the country or until the 
sponsor terminates the 
study in that country). 
Visit 11 Neurological Exam is 
removed from TP2 SoA. 
Updated with a table title [Home 
Pregnancy Test Schedule(in 
addition to clinic visits)]. 
It was added to specify 
the unscheduled clinical 
visits separately than 
scheduled clinic visits. 
Clarifications added throughout 
document regarding the 
extension of the study and its 
impact on endpoint collection, 
analysis, and reporting. 
Section 1.1 Synopsis; Section 3 
Objectives, Estimands and 
Endpoints 
New footnote is added to specify 
which safety endpoints apply to 
TP3. 
Added ECG analysis under 
safety endpoints at TP1 and TP2 
phases only. 
The endpoints were 
updated as a result of the 
study extension. 
ECG was missing in 
previous amendment for 
TP1 and TP2. No ECG 
will be recorded in TP3. 


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PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 3 Objectives, Estimands 
and Endpoints 
Added tertiary/exploratory 
efficacy endpoints, patient- 
centered outcomes and 
biomarkers. 
Added endpoints as a 
result of the study 
extension. 
Section 1.1 Synopsis; Section 1.2 
Schema; Section 1.3.3 Early 
Termination and Follow-up; 
Section 4.1 Overall Design; Section 
7.1.1 Permanent Discontinuation; 
Section 7.1.1.1 Observation Period; 
Added detail on permanent 
discontinuation and defined the 
Observation Period. Added two 
subsections under Section 7.1 
(Section 7.1.1 and Section 
7.1.1.1). 
Added in order to collect 
data in participants who 
have discontinued study 
intervention. 
Section 1.3.2 Intervention Period; 
Section 1.3.3 Early Termination 
and Follow-up; Section 10.2 
Appendix 2: Clinical Laboratory 
Tests; Section 10.7.1 Monitoring; 
Section 10.7.2 Discontinuation; 
Section 10.9.3.1 Laboratory Testing 
(Usual Safety Assessments); 
Section 10.9.3.3 Audiological and 
Neurological Specialist 
Evaluations; Section 10.9.3.4 Skin 
Biopsies; Section 10.9.6. Home 
Health Visits 
Fasting Lipid Panel is not 
collected for participants who 
have completed the Month 15E 
Visit. 
For participants who have 
completed the Month 15E Visit, 
creatine kinase, urine 
myoglobin, skin biopsies and 
neurological testing will not be 
tested. Only audiological testing 
will be collected in TP3. 
For participants who have 
completed the Month 15E Visit, 
urinalysis and neurological 
testing will be performed only if 
considered clinically indicated 
by the investigator. 
These changes were 
made for consistency 
with Section 1.3.2.2 in 
which fasting lipid 
panel, creatine kinase, 
urine myoglobin, 
urinalysis. skin biopsies, 
neurological testing are 
not collected after 
Month 15E Visit. Based 
on recent safety data 
analyses, it has been 
considered that 
measurements of fasting 
lipid panel, creatine 
kinase, urine myoglobin 
(reactive), skin biopsies, 
neurological testing and 
urinalysis are no longer 
warranted after Month 
15E. Note that urinalysis 
and neurological 
evaluation can still be 
performed if considered 
clinically indicated by 
the investigator. 
Section 1.3.3 Early Termination 
and Follow-up; Section 10.7.2 
Discontinuation; Section 10.9.3.2 
Electrocardiograms 
12- lead ECG is not collected 
during ET visit for participants 
who have completed the Month 
15E Visit. 
These changes were 
made for consistency 
with Section 1.3.2.2 in 
which 12-lead ECG is 
not collected after 
Month 15E Visit. 


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PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
The sponsor has 
performed an analysis of 
applicable nonclinical 
and clinical data that 
indicate that the risk for 
PF 06651600 to cause 
clinically meaningful 
QT prolongation in 
humans is low. 
Section 2.2.1 Non-clinical Studies; 
Section 6.1 Study Intervention (s) 
Administered; Section 6.2 
Preparation/Handling/ 
Storage/Accountability; Section 6.4 
Study Intervention Compliance; 
Section 10.9.5. Study Intervention 
PF-06651600 bioequivalence 
between tablets and capsules 
was established in completed 
Phase 1 Study B7981029. 
Dosage form, packaging, and 
labeling updated to allow tablet 
or capsule and blister cards or 
bottles. 
The study extension of 
up to an additional 36 
months of treatment 
beyond Month 24 (15E 
Visit) may result in a 
transition of 
PF-06651600 dosage 
form from tablet to 
capsule and from blister 
cards to bottles. 
Section 2.2.2 Clinical Experience 
Section 2.3. Benefit /Risk 
Assessment 
Updated with the total numbers 
of participants from other Phase 
2 and Phase 3 studies with PF- 
06651600. Phase 2b/3 B7981015 
study information was added 
(Section 2.2.2.2). 
Updated with current benefit and 
risk information of PF-06651600 
from study B7981015. 
Update was made in 
alignment with 
Investigator Brochure 
version 8.0 December 
2021, and also to clarify 
the safety of PF- 
06651600. 
Update was made to 
clarify the safety of PF- 
06651600. 
Section 4.3 Justification for Dose 
Table 1 
Mean Clinical AUC and 
Calculated Safety Margin 
updated. 
This update was made in 
alignment with 
Investigator Brochure 
version 8.0 December 
2021. 
Section 5.3.1 Contraception 
Added additional clarifications 
on the contraception check. 
If in the event the participant 
discontinues contraception 
method, the Investigator will 
“document the requirement to 
use an alternate protocol- 
specified method, including if 
the participant will no longer use 
abstinence as the selected 
contraception method” and “The 
contraception check for WOCBP 
will be performed during each 
This update was made to 
provide additional 
clarification on the 
requirements and timing 
for contraception check. 


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PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
study visit and monthly between 
study visits at time of the phone 
contact to check the at-home 
pregnancy test results.” 
Section 6.3.1 Blinding 
Added sections specifying the 
following: TP1 and initial 4 
weeks of TP2 will be double- 
blinded. For the remainder of 
TP2, participants, investigators 
and site and sponsor staff are 
aware that active therapy is 
being provided; however, study 
intervention packaging may 
remain blinded. After all 
participants have completed 
TP2, the study will be fully 
unblinded to the initial treatment 
assignments, and TP3 will be 
fully unblinded. 
This update was made to 
clarify the blinding 
approach in the study. 
Section 8 Study Assessments and 
Procedures 
Updated the amount of blood to 
be collected from each 
participant in Study B7981037. 
This change was made 
to align with the 
extended Intervention 
Period for up to 
36 additional months. 
Section 8.2.5 Neurological 
Examination 
Updated with the need of 
neurological evaluation by a 
neurologist during TP3 if 
medically indicated. 
This change was made 
to align with the 
extended Intervention 
Period for up to an 
additional 36 months. 
Section 8.2.11.1 Columbia Suicide 
Severity Rating Scale (C-SSRS); 
Section 10.7.2 Discontinuation 
Added details on participants 
with suicidal ideation. 
This update was made to 
provide details on 
participants with 
suicidal ideation and 
discontinuation criteria 
Section 9.4.1 Timing of the 
Analyses; Section 9.4.2 Efficacy 
Analyses; Section 9.4.3 Safety 
Analyses 
Added a new Section 9.4.1 
explaining the scope of the 
efficacy and safety data to be 
included in the 3 analyses; 
Updated the efficacy and safety 
analyses tables, explaining 
details of the specific efficacy 
and safety analysis included in 
each of the three CSRs; added 
how to derive non-AA SALT 
score. 
Updated to offer clarity 
in statistical analyses for 
additional 36 months 
extension period 


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PFIZER CONFIDENTIAL 
Page 6 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 9.5 Interim Analyses 
Clarified when an interim 
analysis may be needed eg, for 
study monitoring for internal 
decision making, due to 
regulatory requests, or to support 
regulatory submissions. 
This update was made to 
specify the timing of 
interim analysis in this 
study. 
Section 10.1.5.2 
Adjudication/Review Committee 
Submission 
Updated language regarding 
events requiring submission to 
an adjudication/review 
committee. 
This update was made to 
provide clarification on 
events requiring 
submission to an 
adjudication/review 
committee. 
Section 10.4: Appendix 4: 
Contraceptive Guidance and 
Collection of Pregnancy 
Information 
Updated text regarding 
confirmation of post-menopausal 
status during the study. 
This update was made to 
provide additional 
clarification on the 
procedure for 
confirming 
postmenopausal status 
Section 10.7.1 Monitoring 
Updated hemoglobin values 
requiring re-testing in Table 3. 
Based on a recent 
review of clinical safety 
data for PF-06651600 
and a review of cases 
meeting the ≥2 g/dL 
change from baseline 
threshold in this study, it 
has been considered that 
this criterion is no 
longer warranted, and 
that a participant’s 
safety is adequately 
monitored based on re- 
testing required for 
absolute hemoglobin 
values <10.0 g/dL. 
Section 10.9.2 Telehealth Visits 
Updated language for WOCBP 
referencing Section 5.3.1. 
“Contraception”. 
This update was made 
for clarity and 
consistency with Section 
5.3.1. 
Section 10.9.3.1 Laboratory Testing 
(Usual Safety Assessments) 
Updated with Tuberculosis 
testing 
Table 4 was updated with the 
additional visits in 36 months 
extension period. Visit days 
were corrected. 
Updated to be consistent 
with the changes made 
for 36-month study 
extension. 


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PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 10.11 Appendix 11: 
Protocol Amendment History 
Moved table for Amendment 1 
descriptions of changes and brief 
rationales to this appendix. 
The version date is corrected to 
April 23, 2021. 
Following Pfizer’s 
standard procedure for 
the common protocol 
template. 
The version date was 
revised based on the 
date of last sign-off date. 
Throughout document 
Other relatively minor 
administrative/typo/formatting/ 
Abbreviations updates. 
Updated for 
grammatical correctness, 
clarity, consistency with 
Pfizer Global Style 
Guide and protocol 
template. 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs 


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PFIZER CONFIDENTIAL 
Page 8 
 
 
TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 14 
1. PROTOCOL SUMMARY ................................................................................................... 15 
1.1. Synopsis ................................................................................................................... 15 
1.2. Schema..................................................................................................................... 19 
1.3. Schedule of Activities .............................................................................................. 20 
1.3.1. Screening and Day 1 ................................................................................... 20 
1.3.2. Intervention Period ...................................................................................... 23 
1.3.2.1. Treatment Periods 1 and 2 (TP1 and TP2): Day 1 to 
Month 15E ......................................................................................... 23 
1.3.2.2. Treatment Period 3 (TP3) .......................................................... 33 
1.3.3. Early Termination and Follow-up ............................................................... 36 
2. INTRODUCTION ................................................................................................................ 42 
2.1. Study Rationale ........................................................................................................ 42 
2.2. Background .............................................................................................................. 42 
2.2.1. Nonclinical Studies ..................................................................................... 43 
2.2.2. Clinical Experience ..................................................................................... 44 
2.2.2.1. Phase 2a Study in Alopecia Areata ............................................ 45 
2.2.2.2. Phase 2b/3 Study in Alopecia Areata ........................................ 46 
2.2.2.3. Phase 2a Study in Rheumatoid Arthritis .................................... 48 
2.3. Benefit/Risk Assessment ......................................................................................... 48 
2.3.1. Risk Assessment ......................................................................................... 50 
3. OBJECTIVES, ESTIMANDS AND ENDPOINTS ............................................................. 51 
4. STUDY DESIGN ................................................................................................................. 52 
4.1. Overall Design ......................................................................................................... 52 
4.2. Scientific Rationale for Study Design ..................................................................... 54 
4.3. Justification for Dose ............................................................................................... 55 
4.4. End of Study Definition ........................................................................................... 56 
5. STUDY POPULATION ...................................................................................................... 56 
5.1. Inclusion Criteria ..................................................................................................... 56 
5.2. Exclusion Criteria .................................................................................................... 58 
5.3. Lifestyle Considerations .......................................................................................... 65 


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5.3.1. Contraception ............................................................................................. 65 
5.3.2. Meals and Dietary Restrictions .................................................................. 65 
5.3.3. Caffeine and Tobacco................................................................................. 65 
5.3.4. Elective Surgery ......................................................................................... 65 
5.4. Screen Failures ........................................................................................................ 66 
6. STUDY INTERVENTION ................................................................................................. 66 
6.1. Study Intervention(s) Administered ........................................................................ 66 
6.2. Preparation/Handling/Storage/Accountability ......................................................... 68 
6.2.1. Preparation and Dispensing ........................................................................ 69 
6.3. Measures to Minimize Bias: Randomization and Blinding .................................... 70 
6.3.1. Blinding ...................................................................................................... 70 
6.4. Study Intervention Compliance .............................................................................. 70 
6.5. Concomitant Therapy ............................................................................................. 71 
6.5.1. Permitted Concomitant Medications .......................................................... 72 
6.5.2. Prohibited Concomitant Medications ......................................................... 72 
6.5.3. Vaccinations ............................................................................................... 73 
6.5.4. Surgery ....................................................................................................... 73 
6.6. Dose Modification .................................................................................................. 73 
6.7. Intervention after the End of the Study .................................................................. 73 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................... 73 
7.1. Discontinuation of Study Intervention .................................................................... 73 
7.1.1. Permanent discontinuation ......................................................................... 73 
7.1.1.1. Observation Period ................................................................... 74 
7.1.2. Temporary Discontinuation ........................................................................ 74 
7.2. Participant Discontinuation/Withdrawal from the Study ....................................... 74 
7.2.1. Withdrawal of Consent .............................................................................. 75 
7.3. Lost to Follow up .................................................................................................... 75 
8. STUDY ASSESSMENTS AND PROCEDURES .............................................................. 76 
8.1. Efficacy Assessments ............................................................................................. 78 
8.1.1. Rater Qualifications ................................................................................... 78 
8.1.2. Clinical Assessments .................................................................................. 78 


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8.1.2.1. Severity of Alopecia Tool (SALT) ............................................ 78 
8.1.3. Patient Reported Outcomes ......................................................................... 79 
8.1.3.1. Patient’s Global Impression of Change (PGI-C) ....................... 79 
8.2. Safety Assessments .................................................................................................. 79 
8.2.1. Medical History, Physical Examinations, Height and Weight .................... 79 
8.2.2. Vital Signs ................................................................................................... 80 
8.2.3. Chest Radiography ...................................................................................... 81 
8.2.4. Electrocardiograms ...................................................................................... 81 
8.2.5. Neurological Examination .......................................................................... 81 
8.2.6. Audiological Evaluations ............................................................................ 82 
8.2.7. Brainstem Auditory Evoked Potential Evaluations .................................... 83 
8.2.8. Skin Punch Biopsy, Evaluation of IENFD and Axonal Dystrophy ............ 83 
8.2.8.1. Skin Punch Biopsy .................................................................... 83 
8.2.8.2. Histology for Axonal Dystrophy and IENFD ............................ 84 
8.2.9. Special Safety Assessment .......................................................................... 84 
8.2.9.1. Suspected Opportunistic Infections ........................................... 84 
8.2.9.2. Dermatological Events .............................................................. 84 
8.2.10. Clinical Safety Laboratory Assessments ................................................... 85 
8.2.10.1. Tuberculosis Testing ................................................................ 85 
8.2.10.2. Day 1 Viral Screen ................................................................... 87 
8.2.10.3. Hepatitis B Virus DNA (HBVDNA) Testing .......................... 88 
8.2.11. Suicidal Ideation and Behavior Risk Monitoring ...................................... 88 
8.2.11.1. Columbia Suicide Severity Rating Scale (C-SSRS) ................ 88 
8.2.12. Patient Health Questionnaire – 8 Items (PHQ-8) ...................................... 88 
8.2.13. Pregnancy Testing ..................................................................................... 88 
8.2.14. Rater Qualifications .................................................................................. 89 
8.3. Adverse Events and Serious Adverse Events .......................................................... 90 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ....... 90 
8.3.1.1. Reporting SAEs to Pfizer Safety ............................................... 91 
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF .................. 91 
8.3.2. Method of Detecting AEs and SAEs ........................................................... 91 
8.3.3. Follow-up of AEs and SAEs ....................................................................... 91 


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8.3.4. Regulatory Reporting Requirements for SAEs ........................................... 92 
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ........................................................................................................... 92 
8.3.5.1. Exposure During Pregnancy ...................................................... 92 
8.3.5.2. Exposure During Breastfeeding ................................................. 94 
8.3.5.3. Occupational Exposure .............................................................. 94 
8.3.6. Cardiovascular and Death Events ................................................................ 94 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................. 95 
8.3.8. Adverse Events of Special Interest ............................................................. 95 
8.3.8.1. Lack of Efficacy ........................................................................ 95 
8.3.9. Medical Device Deficiencies ...................................................................... 95 
8.3.10. Medication Errors ...................................................................................... 95 
8.4. Treatment of Overdose ............................................................................................ 96 
8.5. Pharmacokinetics ..................................................................................................... 96 
8.6. Pharmacodynamics .................................................................................................. 96 
8.7. Genetics ................................................................................................................... 96 
8.7.1. Specified Genetics ....................................................................................... 96 
8.7.2. Banked Biospecimens for Genetics ............................................................. 96 
8.8. Biomarkers ............................................................................................................... 96 
8.8.1. Specified Gene Expression (RNA) Research ............................................. 96 
8.8.2. Specified Protein Research .......................................................................... 97 
8.8.3. Specified Metabolomic Research ................................................................ 97 
8.8.4. Banked Biospecimens for Biomarkers ........................................................ 97 
8.9. Immunogenicity Assessments ................................................................................. 97 
8.10. Health Economics .................................................................................................. 97 
9. STATISTICAL CONSIDERATIONS ................................................................................. 98 
9.1. Estimands and Statistical Hypotheses ..................................................................... 98 
9.2. Sample Size Determination ..................................................................................... 98 
9.3. Analysis Sets ............................................................................................................ 98 
9.4. Statistical Analyses .................................................................................................. 98 
9.4.1. Timing of the Analyses ............................................................................... 99 
9.4.2. Efficacy Analyses ....................................................................................... 99 


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9.4.3. Safety Analyses ........................................................................................ 101 
9.5. Interim Analyses ................................................................................................... 102 
9.6. Data Monitoring Committee or Other Independent Oversight Committee .......... 103 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................ 104 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............. 104 
10.1.1. Regulatory and Ethical Considerations .................................................. 104 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ...................................................................... 104 
10.1.2. Financial Disclosure ............................................................................... 105 
10.1.3. Informed Consent Process ..................................................................... 105 
10.1.4. Data Protection ....................................................................................... 106 
10.1.5. Committees Structure ............................................................................. 106 
10.1.5.1. Data Monitoring Committee ................................................. 106 
10.1.5.2. Adjudication/Review Committee Submission ...................... 106 
10.1.6. Dissemination of Clinical Study Data .................................................... 107 
10.1.7. Data Quality Assurance .......................................................................... 108 
10.1.8. Source Documents ................................................................................. 109 
10.1.9. Study and Site Start and Closure ............................................................ 110 
10.1.10. Publication Policy ................................................................................ 110 
10.1.11. Sponsor’s Qualified Medical Personnel ............................................... 111 
10.2. Appendix 2: Clinical Laboratory Tests .............................................................. 112 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting .................................................................... 114 
10.3.1. Definition of AE ..................................................................................... 114 
10.3.2. Definition of SAE .................................................................................. 115 
10.3.3. Recording and Follow-Up of AE and/or SAE ....................................... 116 
10.3.4. Reporting of SAEs ................................................................................. 119 
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information ............................................................................................................. 120 
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments ...... 123 
10.6. Appendix 6: Hepatitis B Testing Alogrithm and Full Eligibility Criteria .......... 125 
10.7. Appendix 7: Guidelines for Participant Safety Monitoring and 


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Discontinuations ...................................................................................................... 126 
10.7.1. Monitoring ............................................................................................. 126 
10.7.2. Discontinuation ...................................................................................... 127 
10.8. Appendix 8: Prohibited and Permitted Concomitant CYP3A Inducers and 
Substrates ................................................................................................................ 130 
10.8.1. Prohibited Concomitant CYP3A Inducers and Substrates ..................... 130 
10.8.2. Permitted Concomitant CYP3A Substrates ........................................... 131 
10.9. Appendix 9: Alternative Measures During Public Emergencies ........................ 132 
10.9.1. Eligibility ............................................................................................... 132 
10.9.2. Telehealth Visits ..................................................................................... 133 
10.9.3. Alternative Facilities for Safety Assessments ........................................ 134 
10.9.3.1. Laboratory Testing (Usual Safety Assessments) .................. 134 
10.9.3.2. Electrocardiograms ............................................................... 136 
10.9.3.3. Audiological and Neurological Specialist Evaluations ........ 136 
10.9.3.4. Skin Biopsies ........................................................................ 136 
10.9.4. Month 9 Visit Window .......................................................................... 136 
10.9.5. Study Intervention .................................................................................. 137 
10.9.6. Home Health Visits ................................................................................ 138 
10.9.7. Adverse Events and Serious Adverse Events......................................... 139 
10.9.8. Efficacy Assessments ............................................................................. 139 
10.10. Appendix 10: Abbreviations ............................................................................. 140 
10.11. Appendix 11: Protocol Amendment 1 History ................................................ 144 
11. REFERENCES ................................................................................................................ 149 


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LIST OF TABLES 
Table 1. 
PF-06651600 Exposure Margins and No Observed Adverse Effects 
Level ........................................................................................................ 55 
Table 2. 
Protocol Required Safety Laboratory Assessments ................................ 112 
Table 3. 
Laboratory Retesting Criteria ................................................................. 126 
Table 4. 
Windows for Remote Visits, Laboratory Sample Collections, and 
Special Safety Assessments if Required due to Public Emergencies 
Including COVID-19 ............................................................................. 135 


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: A PHASE 2a, RANDOMIZED, DOUBLE-BLIND, PLACEBO- 
CONTROLLED STUDY INVESTIGATING THE SAFETY OF RITLECITINIB 
(PF-06651600) IN ADULT PARTICIPANTS WITH ALOPECIA AREATA 
Short Title: PLACEBO-CONTROLLED SAFETY STUDY OF RITLECITINIB (PF- 
06651600) IN ADULTS WITH ALOPECIA AREATA 
Rationale: 
PF-06651600 inhibits Janus kinase 3 (JAK3) and members of the tyrosine kinase family 
expressed in hepatocellular carcinoma (TEC) and is being developed as an oral treatment for 
patients with alopecia areata (AA). This study includes investigation of the clinical relevance 
of changes observed in non-clinical toxicity studies in dogs treated with PF-06651600. 
Specifically, in a 9-month dog study, axonal dystrophy (axonal swelling due to neurofilament 
accumulation without evidence of axonal degeneration) in the central and peripheral nervous 
systems at ≥20 mg/kg/day (a 12-fold exposure multiple relative to the clinical dose of 
50 mg), and functional auditory deficits on brainstem auditory evoked potentials (BAEP) at 
the highest dose of 40 mg/kg/day (a 29-fold exposure multiple relative to the clinical dose of 
50 mg) were observed. Consequently, this study is specifically designed to evaluate the 
safety, including assessment of BAEPs and intraepidermal nerve fiber (IENF) histology in 
skin punch biopsies, of PF-06651600 in adult participants with AA. 
Objectives, Estimands and Endpoints 
Objectives 
Endpoints 
Primary – Safety 
• To assess I-V interwave latency on 
brainstem auditory evoked potentials 
(BAEPs) in adult participants with 
alopecia areata (AA) treated with 
PF-06651600. 
• Change from baseline in I-V 
interwave latency on BAEP at a 
stimulus intensity of 80 decibels 
(dB) at Month 9. 
Secondary – Safety 
• To assess I-V interwave latency on 
BAEPs in adult participants with 
AA treated with PF-06651600. 
• Change from baseline in I-V 
interwave latency on BAEP at a 
stimulus intensity of 80dB at 
Months 6, 9E, and 15E. 
• To assess axonal dystrophy in 
intraepidermal nerve endings over 
time in adult participants with AA 
treated with PF-06651600. 
• Change from baseline in axonal 
dystrophy in skin punch biopsies at 
Month 9 and Month 15E. 


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Objectives 
Endpoints 
• To assess intraepidermal nerve fiber 
density (IENFD) over time in adult 
participants with AA treated with 
PF-06651600. 
• Change from baseline in IENFD in 
skin punch biopsies at Month 9 and 
Month 15E. 
• To assess wave V amplitude on 
BAEP over time in adult participants 
with AA treated with PF-06651600. 
• Change from baseline in amplitude 
of wave V on BAEP at a stimulus 
intensity of 80dB at Months 6, 9, 9E, 
and 15E. 
• To assess presence of wave V on 
BAEP over time in adult participants 
with AA treated with PF-06651600. 
• Absence of wave V on BAEP at 
stimulus intensities ranging from 
80dB to 40dB at Months 6, 9, 9E, 
and 15E. 
• To evaluate the safety and 
tolerability of PF-06651600 in adult 
participants with AA. 
• Incidence of treatment-emergent 
adverse events (TEAEs), treatment- 
emergent serious adverse events 
(TESAEs), and adverse events 
(AEs) leading to discontinuation;a 
• Incidence of clinically significant 
abnormalities in vital signs and 
ECG; a 
• Incidence of clinically significant 
abnormalities in clinical laboratory 
values. a 
Secondary – Efficacy TP1-TP2 
• To evaluate response to PF- 
06651600 measured by the Severity 
of Alopecia Tool (SALT) in adult 
participants with AA. 
• Change from baseline in overall and 
AA SALTb score at Month 51E and 
other time points collected. 
• To evaluate the response to PF- 
06651600 measured by the Patient’s 
Global Impression of Change 
(PGI-C) tool in adult participants 
with AA. 
• PGI-C score response defined as 
greatly improved or moderately 
improved at Month 9 and other time 
points collected. 
a. 
Refer to Section 9.4.1 for specific safety summary included in each study report. 
b. AA SALT is the amount of scalp hair loss due to AA. 
 
Overall Design: 
This study will investigate PF-06651600 in participants with AA. This is a Phase 2a, 
randomized, double-blind, placebo-controlled safety study designed to evaluate the safety 


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and tolerability of PF-06651600, including the assessments of BAEP and IENF, in adults 18 
to ≤50 years of age with ≥25% scalp hair loss due to AA. 
Disclosure Statement: 
This is a Parallel Treatment study with 2 arms that is Investigator, Sponsor, and Participant 
blinded. 
Number of Participants: 
A total of approximately 60 participants will be randomized in the study. 
Intervention Groups and Duration: 
This study will have approximately 60 adults 18 to 50 years of age, randomized 1:1 to 
receive either PF-06651600 or placebo. 
There will be three treatment periods, and an observation period as follows: 
Treatment Period 1(TP1) and Treatment Period 2 (TP2): 
The total duration of participation in TP1 plus TP2 is approximately 26 months. This 
includes up to a 5-week screening period, a 9-month placebo-controlled treatment phase 
(TP1), a 15-month active therapy extension phase (TP2), and a 4-week follow-up period (if 
not proceeding to TP3) (See Section 1.2). Screening will occur within 35 days prior to Day 1 
of the study to confirm that selection criteria for the study are met. At Month 9, the placebo- 
controlled phase will end, and all participants may enter the active therapy extension phase of 
the study and receive PF-06651600. 
At Month 6, any participant with a baseline overall SALT score ≤75 will have the option to 
enter the active therapy extension phase if the overall SALT score at Month 6 has increased 
from baseline by ≥25 points. 
At the time of their Month 15E visit, participants will have the opportunity to enter TP3, as 
described below. In this case, the Follow-up visit will be completed at the end of their 
participation in TP3. 
 
Treatment Period 3 (TP3): 
• TP3 will be of variable length for individual participants; assuming a participant does 
not require discontinuation per protocol, a participant may continue to receive study 
intervention in TP3 for a maximum of an additional 36 months or until availability of 
commercial product in their country, or until the Sponsor terminates the study in that 
country, whichever occurs first. 
• In TP3, participants will receive 50 mg QD of PF-06651600. The total duration of 
participation in TP3 is approximately 37 months, including up to 36 months of study 
intervention and a Follow-up period of 4 weeks after completion or discontinuation of 
study intervention (See Section 1.2 Schema). 


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Observation Period: 
• If study intervention is permanently discontinued, the participant will be asked to 
remain in the study after the Follow-up visit without study intervention and continue 
to comply with study visit schedules for approximately 2 years after the last dose of 
study intervention or until study end, whichever occurs first; refer to Section 7.1.1.1 
for further details. 
Data Monitoring Committee: Yes 
Statistical Methods 
For the primary safety endpoint, there is no formal hypothesis testing. The analyses will be 
descriptive. Summary statistics for each group with 95% confidence intervals (CIs) will be 
provided. Estimands are not applicable since there is no formal statistical hypothesis testing 
for this study. 


 
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1.2. Schema 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 
 
Page 19 


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1.3. Schedule of Activities 
1.3.1. Screening and Day 1 
The Schedule of Activities (SoA) table provides an overview of the protocol visits and 
procedures. Refer to the Study Assessments and Procedures Section 8 of the protocol for 
detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA 
table, in order to conduct evaluations or assessments required to protect the well-being of the 
participant. 
Some procedures conducted as part of the participant’s routine clinical management (eg, 
chest radiograph [CXR] or other appropriate diagnostic imaging such as computed 
tomography or magnetic resonance imaging [MRI]) and obtained before signing the 
informed consent document (ICD) may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the 
time frame defined in the SoA. 
 
Procedure 
Screen 
ing 
Day 
1 
Notes 
Visit Identifier 
1 
2 
Day 1 (Visit 2) is the last day of screening and the first day of 
the placebo-controlled phase for eligible participants. 
Day 
-35 
to -1 
1 
Visit Window (±Days) 
None 
None 
Enrollment procedures 
Informed consent 
X 
Must be obtained before the participant is enrolled in the study 
per Section 10.1.3. 
Inclusion and exclusion 
criteria 
X 
X 
Pre-dose on Day 1. See Section 5.1 and Section 5.2. 
Demography 
X 
Medical and AA 
disease history 
X 
X 
Pre-dose on Day 1. Refer to the CRF completion guidelines for 
specific information regarding medical history information to 
be collected for each group of participants per 
Section 8.2.1. Medical history includes neurological and 
audiological history per 
Section 8.2.5 and Section 8.2.6. 
Smoking, drug, and 
alcohol history 
X 
See Section 8.2.1. 
Medical procedures 
Full physical 
examination, including 
dermatological full 
body examination. 
X 
X 
Pre-dose on Day 1. See Section 8.2.1 and Section 8.2.9.2. 
Neurological evaluation 
by a neurologist 
X 
The examination will include the Neuropathy Assessment. 
Refer to the Manuals for General Neurological and Neuropathy 
Assessments for more information. See Section 8.2.5. 
Audiological evaluation 
and history by an 
audiologist 
X 
Participants must have a full audiological assessment 
completed during screening prior to Day 1. Audiology and 
BAEP evaluations should be done on the same day, with 


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Procedure 
Screen 
ing 
Day 
1 
Notes 
Visit Identifier 
1 
2 
Day 1 (Visit 2) is the last day of screening and the first day of 
the placebo-controlled phase for eligible participants. 
Day 
-35 
to -1 
1 
Visit Window (±Days) 
None 
None 
audiology assessment first. If they cannot be done on the same 
day, assessments must be within 7 days of each other. Refer to 
the Audiology Study Guide for information on the auditory 
testing. Section 8.2.6. 
Vital signs 
X 
X 
Pre-dose on Day 1. Section 8.2.2. 
12-lead ECG 
X 
Section 8.2.4. 
Height 
X 
Section 8.2.1. 
Weight 
X 
X 
Section 8.2.1. 
Chest radiograph 
X 
CXR or other appropriate diagnostic imaging, such as 
computed tomography or MRI, must be taken at screening if 
not performed within 3 months prior to the screening visit. 
Exclusion Criterion 21 in Section 5.2 and Section 8.2.3. 
BAEP Evaluation 
X 
Audiology and BAEP evaluations should be done on the same 
day, with audiology assessment first. If they cannot be done on 
the same day, assessments must be within 7 days of each other. 
Refer to the Manual for BAEP Evaluation for additional 
information. 
See Section 8.2.7. 
Laboratory 
Hematology and Serum 
Chemistry 
X 
X 
Pre-dose on Day 1. See Section 8.2.10 and Section 10.2 
Fasting Lipid Panel 
X 
See Section 8.2.10 and Section 10.2. 
Urinalysis 
X 
X 
Pre-dose on Day 1. See Section 8.2.9.2.2, Section 8.2.10 and 
Section 10.2 
Serum FSH 
X 
To confirm postmenopausal status in female participants who 
have been amenorrheic for at least 12 consecutive months with 
no alternative pathological or physiological cause. See 
Section 10.2 and Section 10.4. 
Pregnancy test 
(WOCBP only) 
X 
X 
Pre-dose on Day 1. See Section 8.2.13, Section 10.2 and 
Section 10.4. 
HbA1c testing 
X 
See Exclusion Criterion 8 and Section 10.2. 
HIV testing 
X 
See Exclusion Criterion 15 and Section 10.2. 
Hepatitis B and 
Hepatitis C Screening 
X 
See Exclusion Criterion 20, Section 10.2 and Section 10.6. 
HBVDNA (applicable 
countries) 
X 
See Exclusion Criterion 20, Section 8.2.10.3, Section 10.2 and 
Section 10.6. Only for participants negative for HBsAg and 
positive for HBcAb in those regions for which hepatitis B 
prevalence has been reported at a rate of >5.0% or if required 
by local standard of care. 
Skin punch biopsy for 
evaluation of axonal 
dystrophy and IENFD 
X 
Pre-dose. See Section 8.2.8.1. 
Collection of blood 
sample for potential 
viral screen 
X 
Pre-dose. See Section 8.2.10.2, and Section 10.2. 
Tuberculosis testing 
X 
See Exclusion Criterion 21, Section 8.2.10.1, and Section 10.2. 


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Procedure 
Screen 
ing 
Day 
1 
Notes 
Visit Identifier 
1 
2 
Day 1 (Visit 2) is the last day of screening and the first day of 
the placebo-controlled phase for eligible participants. 
Day 
-35 
to -1 
1 
Visit Window (±Days) 
None 
None 
Trial treatment 
IRT registration 
X 
IRT study intervention 
assignment 
X 
Pre-dose. 
Study intervention 
dispensing 
X 
Pre-dose. See Section 6.2. 
Study intervention 
administration 
X 
See Section 6.1. 
Clinical assessments 
SALT 
X 
X 
See Section 8.1.2.1. 
AA eligibility 
assessment 
X 
Scalp hair loss due to AA (AA SALT) to be assessed to verify 
eligibility. See 
Section 8.1.2.1.2. 
C-SSRS 
X 
X 
See Section 8.2.11.1. 
Patient reported outcomes 
PHQ-8 
X 
See Section 8.2.12. 
Other 
Prior and current 
concomitant 
medications and 
treatment(s) monitoring 
X 
X 
See Section 6.5. 
Adverse event 
monitoring 
X 
X 
See Section 8.3 and Section 10.3. 
Contraception check for 
WOCBP 
X 
X 
See Section 5.3.1 and Section 10.4. 
Abbreviations: AA = alopecia areata; BAEP = brainstem auditory evoked potential; CRF=case report form; 
C-SSRS = Columbia Suicide Severity Rating Scale; CXR = Chest radiograph; ECG = electrocardiogram; 
FSH = follicle stimulating hormone; HbA1c= hemoglobin A1c; HBcAb = hepatitis B core antibody; HBsAg 
= hepatitis B surface antigen; HBVDNA = hepatitis B viral deoxyribonucleic acid; HIV = human 
immunodeficiency virus; IENFD = intraepidermal nerve fiber density; IRT = Interactive Response 
Technology; MRI = magnetic resonance imaging; PHQ-8 = Patient Health Questionnaire – 8 items; SALT = 
Severity of Alopecia Tool; WOCBP = women of childbearing potential. 


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1.3.2. Intervention Period 
1.3.2.1. Treatment Periods 1 and 2 (TP1 and TP2): Day 1 to Month 15E 
 
Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Medical Procedures 
Full physical 
examination, 
including 
dermatological 
full body 
examination 
X 
X 
X 
X 
See Section 8.2.1. 
Targeted 
physical 
examination 
X 
X 
X 
X 
X 
See Section 8.2.1. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Neurological 
examination by 
a neurologist 
X 
(see 
Note) 
X 
X 
Neurological examination will include the 
Neuropathy Assessment. Refer to the Manuals for 
General Neurological and Neuropathy Assessments 
for more information. See 
Section 8.2.5. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 
(See Section 4.1). 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.2.2. 
12-lead ECG 
X 
(see 
Note) 
X 
X 
See Section 8.2.4. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Weight 
X 
(see 
Note) 
X 
X 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
Audiological 
Evaluation by 
an audiologist 
X 
X 
X 
X 
At each intervention period, audiology and BAEP 
evaluations should be done on the same day, with 
audiology assessment first. If they cannot be done on 
the same day, assessments must be within 7 days of 
each other. Refer to the Audiology Study Guide for 
information on the auditory testing. See 
Section 8.2.6. 
BAEP 
Evaluation 
X 
X 
X 
X 
At each intervention period, audiology and BAEP 
evaluations should be done on the same day, with 
audiology assessment first. If they cannot be done on 
the same day, assessments must be within 7 days of 
each other. Refer to the Manual for BAEP Evaluation. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
See 
Section 8.2.7. 
Laboratory 
Hematology and 
Serum 
Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.2.10 and Section 10.2. 
Fasting Lipid 
Panel 
X 
(see 
Note) 
X 
X 
See Section 8.2.10 and Section 10.2. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.2.10 and Section 10.2. 
Pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
For WOCBP only. 
Monthly urine pregnancy tests for home testing will 
be performed by the participant between scheduled 
study visits starting after the Month 1 visit through 
the 15E visit. Pregnancy tests for home testing will be 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
provided for testing between visits. Site personnel 
will contact participants between study visits to 
obtain monthly pregnancy test result and ensure this 
contact and the result of the pregnancy test are 
recorded in participant source documentation and 
CRF. See Section 8.2.13, Section 10.2, and 
Section 10.4. 
HBVDNA 
(applicable 
countries) 
X 
X 
(see 
Note) 
X 
X 
X 
X 
X 
X 
Only for participants who were enrolled with a 
positive HBcAb and a negative HBVDNA in those 
regions for which hepatitis B prevalence has been 
reported at a rate of >5.0% or if required by local 
standard of care. Testing at additional time points 
may be performed as per the local standard of care. 
See Section 8.2.10.3, Section 10.2, and Section 10.6. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
Skin punch 
biopsy for 
evaluation of 
axonal 
dystrophy and 
IENFD 
X 
(see 
Note) 
X 
X 
See Section 8.2.8.1. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
Note: At the EOP visit (Month 6 or Month 9/EOP, as 
appropriate), the skin biopsy must be collected before 
the start of Active Therapy Extension Phase. 
Tuberculosis 
testing 
X 
(see 
Note) 
X 
X 
See Section 8.2.10.1, Section 8.2.3, and Section 10.2. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
Trial Treatment 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
IRT study 
intervention 
assignment 
X 
(see 
Note) 
X 
IRT will be contacted at Month 9 for participants 
entering the active therapy extension phase for study 
intervention assignment. 
Note: IRT will be contacted at Month 6 for 
participants entering the active therapy extension 
phase at Month 6 for study intervention assignment. 
Study 
intervention 
dispensing 
X 
X 
X 
X 
X 
X 
X 
X 
At the Month 1 visit and each visit thereafter, the 
participant will return the package containing the 
study intervention which was dispensed at the 
previous visit for accountability. See Section 6.2. 
At the Month 6 visit (only for those eligible 
participants who enter the active therapy extension 
phase at Month 6 [see Section 4.1]) or 9/EOP visit, if 
the neurological or audiological/BAEP assessments 
have not yet been completed, double-blind therapy 
continues to be dispensed until the neurological and 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
audiological/BAEP assessments (including the central 
read confirmation and any repeat assessments if 
deemed necessary by the central reader) are 
completed. Active therapy is dispensed (via on-site 
visit or shipping) only once all the above procedures 
are completed. Refer to the IRT reference manual for 
dispensing additional double-blind therapy. 
Study 
intervention 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 6.1. 
Study 
intervention 
accountability 
and compliance 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 6.2 and Section 6.4. 
Clinical Assessments 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
SALT 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.1.2.1. At Month 6, any participant with 
a baseline overall SALT score ≤75 will have the 
option to enter the active therapy extension phase if 
the overall SALT score at Month 6 has increased 
from baseline by ≥25 points. 
Non-AA SALT 
X 
(see 
Note) 
X 
X 
Only participants with other known etiologies of 
scalp hair loss in addition to AA. See 
Section 8.1.2.1.1. 
Note: Assessment at Month 6 is required only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 (See Section 4.1). 
C-SSRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.2.11.1. 
Patient reported outcomes 
PGI-C 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.1.3.1. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP1: Placebo-controlled 
Phase 
TP2: Active Therapy Extension Phase 
Visit Identifier 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Visit 6 (Month 9/EOP), the last visit of the placebo- 
controlled phase, is also the first visit of the active 
therapy extension phase. 
Visit (Months) 
1 
3 
6 
9 / 
EOP 
3E 
6E 
9E 
12E 
15E 
E=Active Therapy Extension Phase 
Note: Those participants who enter the active therapy 
extension phase at Month 6 (Visit 5) are to complete 
at that visit all Month 6 (Visit 5) assessments and then 
follow the schedule of visits in the active therapy 
extension phase starting with Month 3E, 
Day 
31 
91 
181 
271 
91E 
181E 
271E 
361E 
451E 
Day relative to the start of the study phase (ie, Day 1 
= start of Placebo-controlled Phase; Day 1E = start of 
Active Therapy Extension Phase). 
Visit Window 
(±Days) 
±3 
±7 
±7 
(See 
Note) 
±7 
(See 
Note) 
±7 
±7 
±7 
±7 
±7 
Note: For the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any repeat 
assessments if deemed necessary by the central 
reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Other 
Prior and 
current 
concomitant 
medication(s) 
and treatment(s) 
monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 6.5. 
Adverse event 
monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.3 and Section 10.3. 
Contraception 
check for 
WOCBP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 5.3.1 and Section 10.4. 
Abbreviations: AA = alopecia areata; BAEP = brainstem auditory evoked potential; CRF = case report form; C-SSRS = Columbia Suicide Severity Rating Scale; 
ECG = electrocardiogram; EOP = End of placebo-controlled phase/ beginning of active therapy extension phase; EOT = End of Treatment; HBcAb = hepatitis B core antibody; 
HBVDNA = hepatitis B viral deoxyribonucleic acid; IENFD = intraepidermal nerve fiber density; IRT = Interactive Response Technology; PGI-C = Patient’s global impression 
of change; SALT = Severity of Alopecia Tool; WOCBP = women of childbearing potential. 


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Home Pregnancy Test Schedule (in addition to clinic visits) 
Procedure 
Intervention Period 
Phase: 
TP1: Placebo-controlled Phase 
TP2: Active Therapy Extension Phase 
Month 
2 
4 
5 
7 
8 
1E 
2E 
5E 
7E 
8E 
10E 
11E 
13E 
14E 
Home pregnancy 
test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
1.3.2.2. Treatment Period 3 (TP3) 
 
Procedure 
Intervention Period 
Notes 
Phase: 
TP3: Extension Phase 
Visit Identifier 
12 
13 
14 
15 
16 
17/EOT 
Visit (Months) 
21E 
27E 
33E 
39E 
45E 
51E 
Note: Those participants who enter Extension Phase TP3 at 
Month 15E (Visit 11) are to complete at that visit all Month 15E 
(Visit 11) assessments and then follow the schedule of visits in 
Extension Phase, starting with Month 21E (Visit 12). 
Day 
631E 
811E 
991E 
1171E 
1351E 
1531E 
Day relative to the start of the study phase (Day 1E = start of 
Active Therapy Extension Phase TP2) 
Visit Window 
(±Days) 
±7 
±7 
±7 
±7 
±7 
±7 
Full physical 
examination, 
including 
dermatological full 
body examination 
X 
X 
X 
See Section 8.2.1. 
Targeted physical 
examination 
X 
X 
X 
See Section 8.2.1. 
Vital signs 
X 
X 
X 
X 
X 
X 
See Section 8.2.2. 
Weight 
X 
X 
X 
Audiological 
Evaluation by an 
audiologist 
X 
X 
X 
Refer to the Audiometry Study Guide for information on the 
auditory testing. See 
Section 8.2.6. 
Hematology and 
Serum Chemistry 
X 
X 
X 
X 
X 
X 
For participants who have completed the Month 15E visit, 
creatine kinase will not be tested. See Section 8.2.10 and 
Section 10.2. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP3: Extension Phase 
Visit Identifier 
12 
13 
14 
15 
16 
17/EOT 
Visit (Months) 
21E 
27E 
33E 
39E 
45E 
51E 
Note: Those participants who enter Extension Phase TP3 at 
Month 15E (Visit 11) are to complete at that visit all Month 15E 
(Visit 11) assessments and then follow the schedule of visits in 
Extension Phase, starting with Month 21E (Visit 12). 
Day 
631E 
811E 
991E 
1171E 
1351E 
1531E 
Day relative to the start of the study phase (Day 1E = start of 
Active Therapy Extension Phase TP2) 
Visit Window 
(±Days) 
±7 
±7 
±7 
±7 
±7 
±7 
Urinalysis 
X 
X 
X 
X 
X 
X 
For participants who have completed the Month 15E visit, 
urinalysis will be performed only if considered clinically 
indicated by the investigator. 
See Section 8.2.10 and Section 10.2. 
Pregnancy test 
X 
X 
X 
X 
X 
X 
For WOCBP only. 
∗ Monthly urine pregnancy tests for home testing will be 
performed by the participant between all scheduled study visits 
through to the 51E/EOT visit. Pregnancy tests for home testing 
will be provided for testing between visits. Site personnel will 
contact participants between study visits to obtain monthly 
pregnancy test results and ensure these contacts and the results of 
the pregnancy tests are recorded in participant source 
documentation and CRF.See Section 8.2.13, Section 10.2, and 
Section 10.4. 
HBVDNA (applicable 
countries) 
X 
X 
X(see 
Note) 
X 
X 
X 
Only for participants who were enrolled with a positive HBcAb 
and a negative HBVDNA in those regions for which hepatitis B 
prevalence has been reported at a rate of >5.0% or if required by 
local standard of care. Testing at additional time points may be 
performed as per the local standard of care. See Section 8.2.10.3, 
Section 10.2, and Section 10.6. 
Tuberculosis testing 
X 
X 
X 
See Section 8.2.10.1, Section 8.2.3, and Section 10.2. 
IRT study 
intervention 
assignment 
IRT will be contacted at Month 15E for participants entering 
Extension Phase TP3 for study intervention assignment. 
Study intervention 
dispensing 
X 
X 
X 
X 
X 
X 
The participant will return the package containing the study 
intervention which was dispensed at the previous visit for 
accountability.See Section 6.2. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP3: Extension Phase 
Visit Identifier 
12 
13 
14 
15 
16 
17/EOT 
Visit (Months) 
21E 
27E 
33E 
39E 
45E 
51E 
Note: Those participants who enter Extension Phase TP3 at 
Month 15E (Visit 11) are to complete at that visit all Month 15E 
(Visit 11) assessments and then follow the schedule of visits in 
Extension Phase, starting with Month 21E (Visit 12). 
Day 
631E 
811E 
991E 
1171E 
1351E 
1531E 
Day relative to the start of the study phase (Day 1E = start of 
Active Therapy Extension Phase TP2) 
Visit Window 
(±Days) 
±7 
±7 
±7 
±7 
±7 
±7 
Study intervention 
administration 
X 
X 
X 
X 
X 
See Section 6.1. 
Study intervention 
accountability and 
compliance 
X 
X 
X 
X 
X 
X 
See Section 6.2 and Section 6.4. 
SALT 
X 
X 
X 
X 
X 
X 
See Section 8.1.2.1. 
Non-AA SALT 
X 
Only participants with other known etiologies of scalp hair loss in 
addition to AA. See 
Section 8.1.2.1.1. 
C-SSRS 
X 
X 
X 
X 
X 
X 
See Section 8.2.11.1. 
PGI-C 
X 
X 
X 
X 
X 
X 
See Section 8.1.3.1. 
Prior and current 
concomitant 
medication(s) and 
treatment(s) 
monitoring 
X 
X 
X 
X 
X 
X 
See Section 6.5. 
Adverse event 
monitoring 
X 
X 
X 
X 
X 
X 
See Section 8.3 and Section 10.3. 
Contraception check 
for WOCBP 
X 
X 
X 
X 
X 
X 
See Section 5.3.1 and Section 10.4. 
Abbreviations: AA = alopecia areata; CK = creatine kinase; CRF = case report form; C-SSRS = Columbia Suicide Severity Rating Scale; EOP = End of placebo-controlled phase/ 
beginning of active therapy extension phase; EOT = End of Treatment; HBcAb = hepatitis B core antibody; HBVDNA = hepatitis B viral deoxyribonucleic acid; IENFD = 
intraepidermal nerve fiber density; IRT = Interactive Response Technology; PGI-C = Patient’s global impression of change; SALT = Severity of Alopecia Tool; WOCBP = 
women of childbearing potential. 


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Procedure 
Intervention Period 
Notes 
Phase: 
TP3: Extension Phase 
Visit Identifier 
12 
13 
14 
15 
16 
17/EOT 
Visit (Months) 
21E 
27E 
33E 
39E 
45E 
51E 
Note: Those participants who enter Extension Phase TP3 at 
Month 15E (Visit 11) are to complete at that visit all Month 15E 
(Visit 11) assessments and then follow the schedule of visits in 
Extension Phase, starting with Month 21E (Visit 12). 
Day 
631E 
811E 
991E 
1171E 
1351E 
1531E 
Day relative to the start of the study phase (Day 1E = start of 
Active Therapy Extension Phase TP2) 
Visit Window 
(±Days) 
±7 
±7 
±7 
±7 
±7 
±7 
Note: For participants, who have completed the Month 15E visit, neurological exam by neurologist, BAEP, skin punch biopsy, 12-Lead ECG, fasting lipid panel, CK, urine 
myoglobin,and urinalysis (unless clinically indicated) will not be tested in TP3. 
*Home pregnancy test on all non-scheduled visit months during Observation Period (i.e., 16E-20E, 22E-26E, 28E-32E, 34E-38E, 40E-44E, 46E-50E) 
 
 
1.3.3. Early Termination and Follow-up 
If study intervention is permanently discontinued, the participant will be asked to remain in the study after the Follow-up visit without 
study intervention and continue to comply with study visit schedules for approximately 2 years or until study end, whichever occurs 
first. Refer to Section 4.1 for further details. 


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Procedure 
ET 
28-Day Follow-up 
6-Month 
Follow-up 
Notes 
Visit Identifier 
NA 
18 
19 
Day 
NA 
EOS 
28 days after last dose 
182 days after 
discontinuation 
for neurological 
or auditory 
adverse event 
Visit Window 
(±Days) 
+7 
±7 
±30 
ET visit will be performed on the last day the participant takes 
the study intervention or as soon as possible thereafter. 
Follow-up visit is 28 days after last dose. 
6-Month Follow-up visit occurs 6 months after the last dose of 
study intervention for any participant who discontinues the study 
due to a neurological or auditory adverse event 
(See Section 10.7). 
Medical Procedures 
Full physical 
examination, 
including 
dermatological full 
body examination 
X 
See Section 8.2.1. 
Targeted physical 
examination 
X 
X 
See Section 8.2.1. 
Neurological 
examination by a 
neurologist 
X 
X 
(see Note) 
See Section 10.7.2 for follow-up assessment of participants who 
discontinue due to a neurological adverse event. 
Neurological examination will include the Neuropathy 
Assessment. Refer to the Manuals for General Neurological and 
Neuropathy Assessments for more information. See Section 
8.2.5. 
Neurological examination not collected during ET visit for 
participants who have completed the Month 15E visit, unless 
these assessments are relevant to the reason for discontinuation. 
If neurological examination required, the same neurologist who 
saw the participant for the first 24 months should also do the 
consultation when possible. 
Vital Signs 
X 
X 
X 
See Section 8.2.2. 


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Procedure 
ET 
28-Day Follow-up 
6-Month 
Follow-up 
Notes 
Visit Identifier 
NA 
18 
19 
Day 
NA 
EOS 
28 days after last dose 
182 days after 
discontinuation 
for neurological 
or auditory 
adverse event 
Visit Window 
(±Days) 
+7 
±7 
±30 
ET visit will be performed on the last day the participant takes 
the study intervention or as soon as possible thereafter. 
Follow-up visit is 28 days after last dose. 
6-Month Follow-up visit occurs 6 months after the last dose of 
study intervention for any participant who discontinues the study 
due to a neurological or auditory adverse event 
(See Section 10.7). 
12-lead ECG 
X 
See Section 8.2.4. 
12-lead ECG is not to be collected during ET visit for 
participants who have completed the Month 15E visit. 
Weight 
X 
See Section 8.2.1. 
Audiological 
Evaluation 
X 
X 
(see Note) 
Audiology and, if applicable, BAEP evaluations should be done 
on the same day, with audiology assessment first. If they cannot 
be done on the same day, assessments must be within 7 days of 
each other. Refer to the Audiology Study Guide for information 
on the auditory testing. 
Section 8.2.6. 
See Section 10.7.2 for follow-up assessment of participants who 
discontinue due to an auditory adverse event. 
Note: Assessments as relevant to the reason for discontinuation 


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Procedure 
ET 
28-Day Follow-up 
6-Month 
Follow-up 
Notes 
Visit Identifier 
NA 
18 
19 
Day 
NA 
EOS 
28 days after last dose 
182 days after 
discontinuation 
for neurological 
or auditory 
adverse event 
Visit Window 
(±Days) 
+7 
±7 
±30 
ET visit will be performed on the last day the participant takes 
the study intervention or as soon as possible thereafter. 
Follow-up visit is 28 days after last dose. 
6-Month Follow-up visit occurs 6 months after the last dose of 
study intervention for any participant who discontinues the study 
due to a neurological or auditory adverse event 
(See Section 10.7). 
BAEP Evaluation 
X 
X 
(see Note) 
Audiology and BAEP evaluations should be done on the same 
day, with audiology assessment first. If they cannot be done on 
the same day, assessments must be within 7 days of each other. 
Refer to the Manual for BAEP Evaluation. Section 8.2.7. 
See Section 10.7.2 for follow-up assessment of participants who 
discontinue due to an auditory adverse event. 
Note: Assessments as relevant to the reason for discontinuation. 
BAEP evaluation not collected during ET visit for participants 
who have completed the Month 15E visit, unless these 
assessments are relevant to the reason for discontinuation. 
Laboratory 
Hematology and 
Serum Chemistry 
X 
X 
For participants who have completed the Month 15E visit, 
creatine kinase will not be tested. 
Section 8.2.10 and Section 10.2. 
Fasting Lipid Panel 
X 
Fasting lipid panel is not to be collected during ET visit for 
participants who have completed the Month 15E visit. 
Section 8.2.10 and Section 10.2. 
Urinalysis 
X 
X 
For participants who have completed the Month 15E visit, 
urinalysis will be performed only if considered clinically 
indicated by the investigator during ET and Follow-up visits. 
See Section 8.2.10 and Section 10.2. 


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Procedure 
ET 
28-Day Follow-up 
6-Month 
Follow-up 
Notes 
Visit Identifier 
NA 
18 
19 
Day 
NA 
EOS 
28 days after last dose 
182 days after 
discontinuation 
for neurological 
or auditory 
adverse event 
Visit Window 
(±Days) 
+7 
±7 
±30 
ET visit will be performed on the last day the participant takes 
the study intervention or as soon as possible thereafter. 
Follow-up visit is 28 days after last dose. 
6-Month Follow-up visit occurs 6 months after the last dose of 
study intervention for any participant who discontinues the study 
due to a neurological or auditory adverse event 
(See Section 10.7). 
Pregnancy test 
(WOCBP only) 
X 
X 
See Section 8.2.13, Section 10.2 and Section 10.4. 
HBVDNA 
(applicable countries) 
X 
Only for participants who were enrolled with a positive HBcAb 
and a negative HBVDNA in those regions for which hepatitis B 
prevalence has been reported at a rate of >5.0% or if required by 
local standard of care. See Section 8.2.10.3 and Section 10.6. 
Skin punch biopsy 
for evaluation of 
axonal dystrophy and 
IENFD 
X 
X 
(see Note) 
See Section 8.2.8.1. See Section 10.7.2 for follow-up assessment 
of participants who discontinue due to a neurological adverse 
event. 
Note: Assessments as relevant to the reason for discontinuation. 
Skin punch biopsies will not be collected during ET visit for 
participants who have completed the Month 24 visit. 
Trial treatment 
Study intervention 
accountability and 
compliance 
X 
See Section 6.2 and Section 6.4. 
Clinical assessments 
SALT 
X 
See Section 8.1.2.1. 
Non-AA SALT 
X 
Only participants with other known etiologies of scalp hair loss 
in addition to AA. See 
Section 8.1.2.1.1. 
C-SSRS 
X 
See Section 8.2.11.1. 


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Procedure 
ET 
28-Day Follow-up 
6-Month 
Follow-up 
Notes 
Visit Identifier 
NA 
18 
19 
Day 
NA 
EOS 
28 days after last dose 
182 days after 
discontinuation 
for neurological 
or auditory 
adverse event 
Visit Window 
(±Days) 
+7 
±7 
±30 
ET visit will be performed on the last day the participant takes 
the study intervention or as soon as possible thereafter. 
Follow-up visit is 28 days after last dose. 
6-Month Follow-up visit occurs 6 months after the last dose of 
study intervention for any participant who discontinues the study 
due to a neurological or auditory adverse event 
(See Section 10.7). 
Patient reported outcomes 
PGI-C 
X 
See Section 8.1.3.1. 
Other 
Prior and current 
concomitant 
medication(s) and 
treatment(s) 
monitoring 
X 
X 
X 
See Section 6.5. 
Adverse event 
monitoring 
X 
X 
X 
See Section 8.3 and Section 10.3. 
Contraception check 
for WOCBP 
X 
X 
See Section 5.3.1 and Section 10.4. 
Abbreviations: AA = alopecia areata; BAEP = brainstem auditory evoked potential; ECG = electrocardiogram; EOS=end of study; ET = Early Termination; 
HBcAb = hepatitis B core antibody; HBVDNA = hepatitis B viral deoxyribonucleic acid; IENFD = intraepidermal nerve fiber density; PGI-C = Patient’s 
global impression of change; SALT = Severity of Alopecia Tool; WOCBP = women of childbearing potential. 


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2. INTRODUCTION 
2.1. Study Rationale 
PF-06651600 is being developed as an oral treatment for patients with alopecia areata (AA) 
based on its mechanism of action and the clinical results obtained in Phase 1 and Phase 2 
studies. This study is specifically designed to evaluate the safety of PF-06651600 in adult 
participants with AA. This includes assessments of brainstem auditory evoked potentials 
(BAEPs) and intraepidermal nerve fiber (IENF) histology. The BAEP and IENF assessments 
are being performed to investigate the clinical relevance of changes observed in non-clinical 
toxicity studies in dogs treated with PF-06651600 (see Section 4.2). 
2.2. Background 
AA is a chronic, relapsing, T-cell mediated autoimmune disorder characterized by non- 
scarring hair loss affecting children and adults across all ages, races, and sexes.(1, 2) AA is 
associated with other immune diseases including asthma, allergic rhinitis, atopic dermatitis, 
and autoimmune diseases such as thyroiditis and vitiligo.(2) 
Clinical presentation of AA can be limited to small, circular patches of scalp hair loss (patchy 
hair loss, alopecia focalis), involve complete loss of hair on the scalp (alopecia totalis [AT]), 
or total loss of hair on the scalp and body (alopecia universalis [AU]).(3) Patchy alopecia is 
the most common form of AA which may develop into the more extensive and often 
treatment-resistant forms of AA, especially with earlier age of onset.(4) It is estimated that 
AA affects as many as 6 to 7 million individuals in the United States (US)(2) and 147 million 
worldwide.(5) 
Depression, anxiety, and panic disorders are often observed in patients with AA and the 
coping mechanisms of AA patients mirror those of grief and bereavement.(6, 7) A substantial 
body of evidence demonstrates a widespread impact of AA on the psychological health of 
both adult and pediatric patients with AA, including impairment in self-esteem, increased 
incidence of anxiety and depressive disorders and other psychological conditions,(8-12) 
problems with social relations,(13) decreased health-related quality of life (HRQoL) and 
general quality of life (QoL), as well as the QoL of their families.(5, 14-21) 
No drugs have been approved for the treatment of AA in most countries/regions, including 
the US and the European Union (EU). Review of the treatment guidelines and 
recommendations indicate that a number of off-label therapies are frequently used after 
assessing factors such as the age of the patient, disease extent, and disease duration. There is 
neither a cure for AA nor is there a therapy convincingly demonstrated to induce and sustain 
remission long term.(22-26) 
CD8+ T cells, natural killer (NK) cells, and mast cells are involved in the pathogenesis of 
AA. The possible inflammatory pathways in AA include cytokines from the type 1 helper 
T cell (TH1) axis, including interferon (IFN) alpha (α), IFN gamma (γ), and IFNγ-induced 
protein 10 (IP-10).(27, 28) Mouse models have shown that interleukin (IL)-2 and IL-15 play a 


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role in the initiation of auto-reactive CD8+ cells that attack hair follicles. IL-12 and IL-23 
may also play a role in the pathogenesis of AA.(29) 
The cytokine signaling pathways of IFNγ and IL-15, among others, can be blocked via Janus 
kinase (JAK) inhibition, supporting the rationale of a JAK inhibitor in the treatment of 
AA.(30) Indeed, treatment with the JAK inhibitors tofacitinib and ruxolitinib is reported to 
reverse AA in a mouse model.(31) Clinically, there are case reports and case series reporting 
that these JAK inhibitors demonstrate efficacy in AA.(31-39) 
The tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family of protein 
kinases consists of five members (Bruton’s tyrosine kinase [BTK], bone marrow tyrosine 
kinase on chromosome X [BMX], interleukin (IL)-2 inducible T cell kinase [ITK], TEC and 
tyrosine kinase expressed in T cells [TXK]), primarily expressed in hematopoietic cells.(40, 41) 
T cells express three TEC kinases, ITK, TEC and TXK that are activated downstream of the 
T cell receptor (TCR). BTK plays crucial roles in B cell development and function and is 
activated downstream of the B cell receptor (BCR). Additionally, TEC kinases have 
overlapping roles in mediating activation signals in NK cells, mast cells and other 
hematopoietic cells.(42) Since CD8+ T cells, NK cells, and mast cells have all been implicated 
in the pathophysiology of AA,(28, 31, 43, 44) inhibition of TEC kinases has the potential to 
contribute to efficacy in this disease by modulating the functional activity of these 
pathogenic effector cells. 
PF‑06651600 is a covalent and irreversible inhibitor of Janus kinase 3 (JAK3) with high 
selectivity over the other three JAK isoforms (JAK1, JAK2, and tyrosine kinase 2 [TYK2]). 
PF‑06651600 also inhibits irreversibly the TEC family kinases with selectivity over the 
broader human kinome. Treatment with PF‑06651600 is expected to inhibit the inflammatory 
pathways mediated by IL‑7, IL‑15, and IL‑21, all implicated in AA. Moreover, due to lack of 
activity against the other JAK isoforms, PF‑06651600 is expected to spare immunoregulatory 
cytokines such as IL‑10, IL‑27 and IL‑35, which are critical to the maintenance of 
immunosuppressive functions and immune homeostasis. 
2.2.1. Nonclinical Studies 
Data from nonclinical studies support the planned clinical trials with PF-06651600; these 
studies are described in the Investigator’s Brochure (IB). 
In the first 9-month study of PF-06651600 in dogs, bilateral axonal dystrophy (not axonal 
degeneration) in the olivary nuclei of the brainstem was observed in males and females 
administered ≥20 mg/kg/day. Auditory testing (BAEP) performed on recovery control and 
high dose animals during the last 2 weeks of the 3-month recovery period showed BAEP 
waveform defects. There was partial recovery in the brainstem microscopic lesions at the end 
of the 3-month recovery period. The no observed adverse effect level (NOAEL) was the 
lowest dose tested of 5 mg/kg/day, based on the adverse finding of axonal dystrophy in the 
brainstem and associated waveform defects in males and females administered 
≥20 mg/kg/day. 


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In the second 9-month study in dogs, PF-06651600-related, minimal to moderate axonal 
dystrophy (axonal swelling due to neurofilament accumulation without evidence of axonal 
degeneration) in the brainstem, minimal axonal dystrophy in the sciatic nerve and branches 
of the vagus nerve, and an increased severity (from minimal to mild) of axonal dystrophy in 
the spinal cord were observed at ≥20 mg/kg/day (a 12-fold exposure multiple relative to the 
clinical dose of 50 mg). Minimal to mild axonal dystrophy was also observed in the white 
matter of the rostral vermis of the cerebellum at ≥10 mg/kg/day. Adverse BAEP findings 
were noted in 1 male and 1 female administered 40 mg/kg/day (a 29-fold exposure multiple 
relative to the clinical dose of 50 mg) at 7 and/or 9 months of dosing, and these findings 
completely recovered at the end of the 6-month recovery in the animal that continued into the 
recovery phase. The auditory deficits observed were consistent with a central, not peripheral, 
effect on auditory function. 
The NOAEL was 10 mg/kg/day, based on adverse over-immunosuppression and axonal 
dystrophy in the central and peripheral nervous system at ≥20 mg/kg/day and accompanied 
by auditory deficits (BAEP) at the highest dose of 40 mg/kg/day. The area under the 
concentration-time curve (AUC) exposure margins in this study at the NOAEL at study end 
were approximately 1.5x and 6.5x relative to the predicted exposure at the 200 mg and 50 mg 
clinical QD doses, respectively (Table 1). 
PF-06651600 bioequivalence between tablets and capsules was established in completed 
Phase 1 Study B7981029. 
For a complete description of these studies please refer to the current version of the IB. 
2.2.2. Clinical Experience 
Data from Phase 1 clinical studies, including pharmacokinetics, bioavailability, and food 
effect, support the planned clinical trials with PF-06651600; these studies are described in the 
IB. 
There are completed and ongoing Phase 2 and 3 studies with PF-06651600 (N=1557) in a 
number of disease indications including rheumatoid arthritis (RA), AA, ulcerative colitis, 
vitiligo, and Crohn’s disease. Forty-two (42) participants with rheumatoid arthritis (RA) were 
exposed to PF-06651600 in the Phase 2a Study B7981006. One hundred and fifty (150) 
participants with ulcerative colitis were exposed to PF-06651600 in the Phase 2b Study 
B7981005. Three hundred and sixty-four (364) and 238 participants with vitiligo were 
exposed to PF-06651600 in the dose-ranging period and in the extension period, respectively, 
of Phase 2b study B7981019. Forty-eight (48) participants were exposed to PF-06651600 in 
the Phase 2a AA Study B7931005 in the initial 24-week period, and 715 participants with 
AA were treated with PF-06651600 in the Phase 2b/3 Study B7981015, with results 
presented below. There are ongoing studies in participants with Crohn’s disease and AA 
(Phase 2a Study B7981007 and Phase 3 Study B7981032 AA LTE). 
For additional descriptions and/or results of these studies, please refer to the current version 
of the PF-06651600 IB. 


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2.2.2.1. Phase 2a Study in Alopecia Areata 
Study B7931005 was a Phase 2a study evaluating the safety, tolerability, pharmacokinetics 
(PK), and efficacy of 2 investigational JAK inhibitors, PF-06700841 and PF-06651600, in 
adult participants with AA (restricted to those with ≥50% scalp hair loss without evidence of 
hair regrowth within the previous 6 months; current episode of hair loss ≤7 years). The study 
included 3 periods: an initial 24-week double-blind treatment period, an up to 48-week 
single-blind extension (SBE) period, and a 24-week cross-over open label extension period. 
During the initial 24-week double-blind treatment period, participants received 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; or a matching placebo for 24 weeks. This 
was followed by an SBE period including a withdrawal/re-treatment period for responders 
and a treatment period for non-responders. After the SBE phase eligible participants could 
enter an open-label cross-over period for non-responders. 
PF-06651600 achieved the primary endpoint, SALT change from baseline, at Week 24. PF- 
06651600 was efficacious compared to placebo as measured by proportion of subjects 
achieving ≥30% and ≥90% improvement from baseline in SALT score (SALT30 
and SALT90). 
PF-06651600 showed continued improvements in the proportion of participants achieving 
various percent improvements from baseline in SALT score (SALT30, SALT50, SALT75, 
SALT90, and SALT100) during the initial 24-week treatment period showing significant 
responses compared to placebo group starting from Week 6 for SALT30, SALT50 and 
SALT 75, Week 12 for SALT90, and at Week 24 for SALT100. 
The proportion of subjects achieving at least 1 grade improvement in both eyelash 
assessment (ELA) and eyebrow assessment (EBA) for PF-06651600 continued to 
increase over the initial double-blind treatment period, significantly differentiating from 
placebo as early as Week 4 for ELA and as early as Week 6 for EBA. 
Participants who received placebo in the initial treatment period followed by PF-06651600 in 
the SBE period had a response consistent with the responses of participants who received PF- 
06651600 during the initial treatment period. There was a loss of efficacy based on SALT30 
compared to the response in the initial treatment period, as SALT30 was only achieved by 
57% of subjects receiving PF-06651600 who had previously responded in the initial 
treatment period. Non-responders who continued treatment for another 24 weeks were 
unlikely to respond during the SBE period. 
Blood samples for PK were collected predose at each visit from baseline to Week 24 as well 
as at 0.5 hours post dose on Weeks 8 and 20; 0.5 and 1 hour post dose on Week 12; and 0.5, 
1, 2, and 4 hours post dose on Weeks 4 and 24. The observed mean Cmax,ss and 
mean AUCtau for 200 mg QD in the AA population were 1601 ng/mL and 6353 ng*hr/mL, 
respectively, slightly higher than the Cmax,ss and AUCtau for 200 mg QD observed in the 
healthy population, 1422 ng/mL and 4069 ng*hr/mL, respectively. 


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PF-06651600 had an acceptable safety profile and was well tolerated. No participants in the 
PF-06651600 group experienced an SAE. During the initial treatment period, the number of 
AEs in the placebo group (105) was higher than in the PF-06651600 group (82), although the 
number of subjects reporting AEs was similar in the placebo and PF-06651600 groups (35 
[74.5%] subjects and 30 [66.7%] subjects, respectively). Two participants in the PF- 
06651600 group discontinued from treatment in the initial treatment period due to an AE 
(angioedema and elevated creatine kinase level, both of which resolved), but continued in the 
study. One active non-responder who received PF-06651600 discontinued from the SBE 
period due to a treatment-emergent adverse event (TEAE) of abnormal liver function test; the 
laboratory values did not reach the criteria for Hy’s Law. 
The most common (≥5%) AEs during the initial treatment period in the PF-06651600 group 
were in the Infections and Infestations (upper respiratory tract infections, nasopharyngitis, 
folliculitis), Gastrointestinal Disorders (nausea, diarrhea), and the Skin and Subcutaneous 
Tissue Disorders (acne, atopic dermatitis) categories, and the majority of events were mild. 
No serious infections or cases of herpes zoster or herpes simplex were reported in the PF- 
06651600 group during the initial treatment period; 1 AE of herpes simplex was reported in 
the PF-06651600 group during the SBE period. 
During the initial treatment period, absolute lymphocyte and platelet counts showed a slight 
decrease from baseline in PF-06651600 treatment group. The mean (90% CI) 
percent CFB absolute neutrophil count in the PF-06651600 treatment group at Week 2 and 
Week 24 was 17.30% (23.12%, -11.47%) and -8.44% (15.59%, -1.29%), respectively. In the 
PF-06651600 treatment group, platelet counts remained slightly lower than baseline value 
with mean (90% CI) percent CFB of -17.89% (-21.32%, -14.47%) and -9.61% 
(13.87%, 5.35%) at Week 2 and Week 24, respectively. There was a decrease in absolute 
lymphocyte count in the PF-06651600 treatment group during the COE period but there was 
no consistent trend in lymphocyte or platelet count during the SBE period. 
There were no clinically significant auditory changes in the active treatment groups. A 
mild TEAE of neurosensory deafness was reported in 1 participant in the placebo group 
during the initial 24-week treatment period. There were no clinically significant findings in 
electrocardiograms (ECG) or vital signs, except increased diastolic blood pressure 
>20 mmHg in 1 participant each on placebo and PF-06651600. 
There were no increased safety risks with re-exposure to PF-06651600 or after cross-over to 
treatment with either PF-06651600 or PF-06700841. The final study results, including the 
results of the two extension periods, are described in the current version of the PF-06651600 
IB. 
2.2.2.2. Phase 2b/3 Study in Alopecia Areata 
B7981015 was a Phase 2b/3, randomized, double blind, placebo controlled, dose ranging 
study to investigate PF-06651600 in both adolescent (≥12 to <18 years old) and adult (≥18 
years old) participants with ≥50% scalp hair loss due to AA. The study had a maximum 
duration of approximately 57 weeks. This included an up to 5-week Screening period, a 48- 
week treatment period, and a 4-week follow up period for participants who did not roll over 


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into the open label long-term Study B7981037. The treatment period was comprised of a 
placebo-controlled period that included a 4-week loading phase and a 20-week maintenance 
phase, followed by a 24-week extension phase. 
Eligible participants were randomized to blinded PF-06651600 and matching placebo in a 
2:2:2:2:1:1:1 (200 mg/50 mg, 200 mg/30 mg, 50 mg, 30 mg, 10 mg, placebo-200 mg/50 mg, 
and placebo-50 mg, respectively) manner for a total of 7 treatment sequences. All 
participants began dosing during the loading phase according to their assigned sequence. 
Following the 4-week loading phase, participants continued dosing according to their 
assigned sequence in the 20-week maintenance phase. At the end of the maintenance phase, 
placebo treated participants were advanced in a prespecified, blinded manner to one of 2 
active treatment sequences for the remainder of the treatment period (through Week 48). 
PF-06651600 200/50 mg, 200/30 mg, 50 mg, and 30 mg were significantly superior to 
placebo at Week 24 on clinician-assessed and patient-reported endpoints related to scalp hair 
regrowth (including response based on absolute SALT ≤20, response based on absolute 
SALT ≤10, and PGI-C response). Exposure response modelling based on SALT ≤20 and 
SALT ≤10 response at Week 24 showed a positive relationship between dose and response. 
PF-06651600 200/50 mg, 200/30 mg, 50 mg, and 30 mg were also nominally superior to 
placebo at Week 24 in producing improvement in eyebrows and eyelashes. Continued 
improvement in efficacy endpoints was seen between Week 24 and Week 48. 
The proportion of participants who experienced all-causality TEAEs was similar across 
treatment groups up to Week 24 (placebo-controlled period) and up to Week 48 (overall). 
The most frequently reported TEAEs in any group included nasopharyngitis, headache, and 
upper respiratory tract infection. Up to Week 24, the incidence of nasopharyngitis, 
folliculitis, urticaria, dizziness, and urinary tract infection was higher in participants treated 
with PF-06651600 (particularly 200/50 mg and 200/30 mg) than placebo. Most TEAEs were 
mild to moderate in severity. Fourteen (14) participants experienced 16 SAEs up to Week 48. 
•200/50 mg (4 participants): appendicitis; empyema and sepsis; invasive lobular breast 
carcinoma, spontaneous abortion 
.•200/30 mg (2 participants): appendicitis; chemical poisoning and suicidal behavior 
.•50 mg (2 participants): breast cancer; pulmonary embolism 
.•30 mg (1 participant): diverticulitis 
.•10 mg (2 participants): suicidal behavior; eczema 
.•Placebo-200/50 mg: no SAEs 
.•Placebo-50 mg (3 participants): spontaneous abortion; conversion disorder; heavy 
menstrual bleeding. These treatment-emergent SAEs were all reported during the 
Placebo-Controlled Period. 


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All SAEs were considered by the investigator as unrelated to study drug, except in 3 
participants (sepsis and empyema, breast cancer, eczema). There were no deaths 
reported in the study. 
Treatment with PF-06651600 was associated with changes in hematological parameters, 
some of which were dose dependent. From Week 4 onward, there were slight, transient 
decreases in hemoglobin and small, variable changes in neutrophil and leukocyte levels. 
Small, early decreases in platelets were observed with PF-06651600 treatment; these levels 
remained stable up to Week 48. Dose-dependent early decreases in absolute lymphocyte 
levels, CD3 (T lymphocytes) and T lymphocyte subsets (CD4 and CD8) were observed. Up 
to Week 24, there was a dose-dependent early decrease in CD16/56 (NK cells), particularly 
in groups who had received a 200 mg loading dose of PF-06651600 for 4 weeks. Overall, 
there were no clinically meaningful effects of PF-06651600 on ALT, AST, bilirubin, or 
alkaline phosphatase. The incidence of elevation in hepatic enzymes was low and not dose 
dependent. Up to Week 48, there were no potential Hy’s law cases. 
For a complete description and results of this study, please refer to the current version of the 
PF-06651600 IB. 
2.2.2.3. Phase 2a Study in Rheumatoid Arthritis 
The completed Phase 2a study B7981006 was an 8-week randomized, double-blind, placebo- 
controlled, parallel-group, multi-center study in participants with moderate-to-severe active 
rheumatoid arthritis (RA) with an inadequate response to methotrexate. A total of 
70 participants were randomized to study treatment; 28 participants received placebo and 
42 participants received PF-06651600. 
PF-06651600 was determined to be safe and well tolerated in this study. There were no 
deaths or SAEs. The TEAEs reported in more than 5% of participants with RA receiving PF- 
06651600 were influenza and lymphopenia. There were no clinically relevant changes in 
vital signs, ECG, or audiometric assessments. For more details, including effects on 
laboratory parameters, please refer to the current version of the IB. 
2.3. Benefit/Risk Assessment 
The preliminary clinical data indicate that PF-06651600 has a favorable benefit:risk profile. 
It provided clinical benefit (scalp hair regrowth) in patients with AA and was determined to 
be well tolerated and to have an acceptable safety profile in the clinical studies to date. 
Reductions in platelet counts and lymphocyte counts were observed during treatment with 
200 mg QD but were not considered clinically meaningful and improved after switching to 
50 mg QD. PF-06651600 is an immunomodulator and, like others in this class, can be 
associated with the potential risk of infections (including serious infections), opportunistic 
infections, and viral reactivation. The risk of infection will be monitored in this study. 
In animal studies, PF-06651600 administration was associated with effects on fetal 
development, including skeletal and visceral organ malformations and lower fetal body 
weights. In the fertility and early embryonic development study in rats, PF-06651600-related 


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higher incidence of preimplantation loss was noted in non-dosed females mated with males 
administered PF-06651600, without effects on sperm or other features of male reproduction. 
When PF-06651600 was administered to healthy women together with an oral contraceptive 
containing ethinyl estradiol and levonorgestrel, the level of ethinyl estradiol in the blood was 
decreased; the clinical significance of this decrease is unknown, however the efficacy of 
estrogen-containing contraceptives may be decreased. 
In the Phase 2b/3 pivotal, dose-ranging Study B7981015 in adult and adolescent participants 
with AA, PF-06651600 was evaluated for 48 weeks. PF-06651600 dose regimens of 200/50 
mg (200 mg QD for 4 weeks followed by 50 mg QD through Week 48), 200/30 mg (200 mg 
QD for 4 weeks followed by 30 mg QD through Week 48), 50 mg (50 mg QD for 4 weeks 
and through Week 48), and 30 mg (30 mg QD for 4 weeks and through Week 48) were 
significantly superior to placebo on clinician-assessed and patient-reported endpoints, 
including SALT ≤10, SALT≤20, and PGI-C response. PF-06651600 was safe and well- 
tolerated in participants treated for up to 48 weeks. No deaths were reported. There were no 
dose-dependent trends in overall SAEs, severe TEAEs, or TEAEs leading to discontinuation. 
There were few serious infections and no opportunistic infections. All TEAEs of herpes 
zoster were mild to moderate and occurred in participants treated with PF-06651600. Dose 
regimens with a 200 mg loading dose had a higher incidence of some TEAEs (eg, folliculitis, 
urticaria, dizziness, influenza, upper respiratory tract infection and urinary tract infection) 
compared to their respective maintenance dose (50 mg or 30 mg) and larger decreases in 
some hematological parameters (such as lymphocytes and lymphocyte subsets). There were 
mild and mostly transient changes in hematological parameters, some of which were dose 
dependent. 
These preliminary clinical data indicate that PF-06651600 at doses up to 200 mg QD for 4 
weeks followed by 50 mg QD for 20 weeks, has a favorable benefit: risk profile and provides 
meaningful clinical benefit in a serious disease with no approved treatment options. This 
study will extend the analysis of benefit: risk for up to 5 years. 
It is not known whether PF-06651600 is secreted into human milk. 
Because of the above and the investigational nature of PF-06651600, it should not be 
administered to pregnant women, breastfeeding women, or fertile women of childbearing 
potential who are unwilling or unable to use contraception as defined in the study protocol. 
Men in the study are not required to use birth control because PF-06651600 is not likely to 
transfer to a partner through semen at pharmacologically relevant blood levels. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-06651600 may be found in the IB, which is the single reference safety 
document (SRSD) for this study. 


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2.3.1. Risk Assessment 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Study Intervention PF-06651600 
Reductions in platelet 
counts and lymphocyte 
counts. 
In Study B7931005, reductions in 
platelet counts and lymphocyte 
counts were observed during 
treatment with PF-06651600 200 
mg QD but were not considered 
clinically meaningful and improved 
after switching to 50 mg QD. 
In participants receiving PF-06651600, 
a 200 mg QD dose will be used only 
for 4 weeks after which they will 
receive 50 mg QD. Clinical laboratory 
test results will be monitored and there 
are pre-specified discontinuation 
criteria based on laboratory test results 
(Section 10.7). 
Potential risk of infections. 
PF-06651600 is an 
immunomodulator and, as such, 
can be associated with the potential 
risk of infections (including serious 
infections), opportunistic 
infections, and viral reactivation. 
Participants with infection history will 
be excluded (See Section 5.2), the risk 
of infection will be monitored in the 
study, and there are discontinuation 
criteria for serious infections (Section 
10.7). 
Potential fetal risk. 
In animals, PF-06651600 was 
associated with fetal changes in 
bones and some internal organs, 
and lower fetal body weights. 
WOCBP who are unwilling or unable 
to use contraception as defined in the 
study protocol will be excluded (See 
Section 5.3.1 and Section 10.4). 
WOCBP will routinely have pregnancy 
tests and will follow discontinuation 
requirements if pregnant 
(Section 8.2.13). 
Potential risk of secreting 
into human milk. 
It is not known whether 
PF-06651600 is secreted into 
human milk. 
Breastfeeding women are not eligible 
to participate in the study. PF- 
06651600 should not be administered 
to breastfeeding women and exposure 
during breastfeeding should be reported 
to Pfizer Safety (See Section 8.3.5.2). 


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3. OBJECTIVES, ESTIMANDS AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary - Safety 
• To assess I-V interwave latency on 
brainstem auditory evoked potentials 
(BAEPs) in adult participants with 
alopecia areata (AA) treated with 
PF-06651600. 
• Change from baseline in I-V 
interwave latency on BAEP at a 
stimulus intensity of 80 decibels 
(dB) at Month 9. 
Secondary - Safety 
• To assess I-V interwave latency on 
BAEPs in adult participants with 
AA treated with PF-06651600. 
• Change from baseline in I-V 
interwave latency on BAEP at a 
stimulus intensity of 80dB at 
Months 6, 9E, and 15E. 
• To assess axonal dystrophy in 
intraepidermal nerve endings over 
time in adult participants with AA 
treated with PF-06651600. 
• Change from baseline in axonal 
dystrophy in skin punch biopsies at 
Month 9 and Month 15E. 
• To assess intraepidermal nerve fiber 
density (IENFD) over time in adult 
participants with AA treated with 
PF-06651600. 
• Change from baseline in IENFD in 
skin punch biopsies at Month 9 and 
Month 15E. 
• To assess wave V amplitude on 
BAEP over time in adult participants 
with AA treated with PF-06651600. 
• Change from baseline in amplitude 
of wave V on BAEP at a stimulus 
intensity of 80dB at Months 6, 9, 9E, 
and 15E. 
• To assess presence of wave V on 
BAEP over time in adult participants 
with AA treated with PF-06651600. 
• Absence of wave V on BAEP at 
stimulus intensities ranging from 
80dB to 40dB at Months 6, 9, 9E, 
and 15E. 
• To evaluate the safety and 
tolerability of PF-06651600 in adult 
participants with AA. 
• Incidence of treatment-emergent 
adverse events (TEAEs), treatment- 
emergent serious adverse events 
(TESAEs), and adverse events 
(AEs) leading to discontinuation;a 
• Incidence of clinically significant 
abnormalities in vital signs and 
ECG;a 


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Objectives 
Endpoints 
• Incidence of clinically significant 
abnormalities in clinical laboratory 
values.a 
Secondary- Efficacy TP1-TP2 
• To evaluate response to PF- 
06651600 measured by the Severity 
of Alopecia Tool (SALT) in adult 
participants with AA. 
• Change from baseline in overall and 
AA SALTb score at Month 9 and 
other time points collected. 
• To evaluate the response to PF- 
06651600 measured by the Patient’s 
Global Impression of Change 
(PGI-C) tool in adult participants 
with AA. 
• PGI-C score response defined as 
greatly improved or moderately 
improved at Month 9 and other time 
points collected. 
Tertiary/Exploratory-Efficacy TP3 
• To evaluate long-term 
response to PF-06651600 
measured by the Severity of 
Alopecia Tool (SALT) in 
adult participants with AA. 
• Change from baseline in overall and 
AA SALTb score at Month 51E and 
other time points collected. 
• To evaluate the long-term 
response to PF-06651600 
measured by the Patient’s 
Global Impression of Change 
(PGI-C) tool in adult 
participants with AA. 
• PGI-C score response defined as 
greatly improved or moderately 
improved at Month 51E and other 
time points collected. 
a. 
Refer to Section 9.4.1 for specific safety summary included in each study report. 
b. AA SALT is the amount of scalp hair loss due to AA. 
 
4. STUDY DESIGN 
4.1. Overall Design 
Study B7981037 is a Phase 2a, randomized, double-blind, parallel group, placebo-controlled 
safety study designed to evaluate the safety and tolerability of PF-06651600, including the 
assessment of BAEP and IENF, in adults with ≥25% scalp hair loss due to AA. 
Approximately 60 adults 18 to 50 years of age will be randomized 1:1 to receive either 
PF-06651600 or placebo. If there are issues related to the integrity of some peripheral nerve 
punch biopsy samples, up to an additional 20 participants may be added at the discretion of 
the Sponsor to ensure adequate numbers of participants with interpretable biopsies. 


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Treatment Period 1 (TP1) and Treatment Period 2 (TP2): 
The total duration of participation in the study for TP1 and TP2 will be approximately 
26 months. 
This includes up to a 5-week screening period, a 9-month placebo-controlled treatment 
phase, a 15-month active therapy extension phase, and a 4-week follow-up period [for 
participants not continuing to TP3 or discontinuation of study intervention (see Schema 
Section 1.2)]. Screening will occur within 35 days prior to Day 1 of the study to confirm that 
selection criteria for the study are met. At Month 9, the placebo-controlled phase will end, 
and all participants may enter the active therapy extension phase of the study and receive PF- 
06651600. For any participant discontinued for a neurological or auditory adverse event, the 
participant will be evaluated again at 6 months after discontinuation; the maximum duration 
of participation in the study for such participants could be approximately 32 months if the 
event occurred at the last visit. 
At Month 6, any participant with a baseline overall SALT score ≤75 will have the option to 
enter the active therapy extension phase if their overall SALT score at Month 6 has increased 
from baseline by ≥25 points. Those participants who enter the active therapy extension phase 
at Month 6 are to complete at that visit all the Month 6 (Visit 5) assessments and then follow 
the schedule of visits in the active therapy extension phase starting with Month 3E skipping 
the Month 9 (Visit 6). 
BAEPs will be measured at screening and at Months 6, 9, 9E, and 15E, or early termination 
for all participants. IENF will be assessed at Day 1, Month 9, and Month 15E, or early 
termination. Participants who enter the active therapy extension phase at Month 6 will have a 
skin punch biopsy taken at Month 6 for IENF assessments instead of at Month 9. The skin 
biopsy must be collected before the start of Active Therapy Extension Phase. 
Participants who discontinue the study due to a neurological or auditory AE will have 
assessments performed at the time of discontinuation and repeated at 6 months after the last 
dose of study intervention (see Section 10.7). 
Treatment Period 3 (TP3): 
The total duration for TP3 will be of variable length for individual participants; assuming a 
participant does not require discontinuation per protocol. A participant may continue to 
receive PF-06651600 in TP3 for a maximum of an additional 36 months or until availability 
of commercial product in their country, or until the Sponsor terminates the study in that 
country, whichever occurs first. 
In TP3, participants will receive 50 mg QD PF-06651600. The total duration of participation 
in TP3 is approximately 37 months, including up to 36 months study intervention, and a 
follow up period of 4 weeks after completion or discontinuation of study intervention (see 
Section 1.2 Schema). 


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Observation Period: 
If study intervention is permanently discontinued, the participant will be asked to remain in 
the study after the Follow-up visit without study intervention, and continue to comply with 
study visit schedules for approximately 2 years after the last dose of study intervention or 
until study end, whichever occurs first; refer to Section 7.1.1.1 for further details. 
 
 
4.2. Scientific Rationale for Study Design 
Because the dog toxicity study BAEP finding was considered a central auditory effect, BAEP 
interwave I-V latency will be the primary endpoint for this study, since generally, the 
interwave latencies are used for diagnosis of brainstem effect in humans.(45) High-intensity 
stimulation (eg, 80dB) is used in humans for differential diagnosis of cochlear versus retro- 
cochlear lesions.(45) 
The total duration of the study is approximately 62 months (26 months [TP1 + TP2] + 36- 
month extension [TP3]), though this duration could be longer for any participant who 
discontinues due to a neurological or auditory AE and needs to return for follow-up in 
6 months. This includes a 9-month placebo-controlled phase that will evaluate the effect of 
PF-06651600 during the same time frame in which axonal dystrophy was observed in the 9- 
month dog toxicity study (ie, axonal dystrophy in the dog studies presented at 9 months and a 
functional correlate [BAEP threshold and waveform abnormality] was evident at 7 and 9 
months). Following the placebo-controlled phase, there will be a 15-month active therapy 
extension phase TP2. The extension phase is included to collect longer-term safety 
information. 
In this study, BAEP will be measured at screening, 6 months, 9 months (the end of the 
placebo-controlled phase), Month 9E, and Month 15E or end of treatment for early 
discontinuation and potentially at a 6-Month Follow-Up. The timepoints for BAEP (not 
measured in TP3) were chosen for the placebo-controlled phase based on the timing of 
findings in the dog toxicity study. The additional 2 measurements during active therapy 
extension phase TP2 are intended to provide longer-term assessment. 
Axonal dystrophy and IENFD will be evaluated in peripheral skin biopsies (TP1 and TP2 
only). The technique allows direct assessments of both morphological features (such as 
axonal dystrophy) as well as IENFD in nerve endings.(46-48) IENFD directly evaluates the loss 
of axons (as an index of axonal degeneration) and its assessment in peripheral skin punch 
biopsies is an established technique used in clinical evaluations of patients with peripheral 
neuropathies. For example, an IENFD study evaluating the structural and functional integrity 
of small autonomic nerve fibers in E46KSNCA (a biomarker for an aggressive Lewy body 
brain disease), carriers showed small fiber neurodegeneration in the skin. In another study, 
distal leg IENFD was shown to detect axonal loss in patients with oxaliplatin-induced 
neuropathy.(49) Also, in a study of patients with diabetic small fiber neuropathy, impaired 
glucose tolerance neuropathy and idiopathic small fiber neuropathy, IENFD loss was seen at 


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three sites (proximal thigh, distal thigh, distal leg) whereas there was no significant change in 
IENFD in healthy controls over 2 to 3 years.(50) 
The distal part of lower extremities will be selected for skin punch biopsies because distal 
portions of long axons are typically more susceptible to axonal dystrophy than proximal 
portions. Axonal dystrophy and IENFD will be measured at Day 1, Month 9, Month 15E, or 
end of treatment for early discontinuation (TP1 and TP2 only), and potentially at 6-Month 
Follow-Up, reflecting the timing of findings in the dog toxicity studies and for longer-term 
assessment. 
Inclusion of patients with ≥25% scalp hair loss due to AA, which the investigator has 
additionally determined to be appropriate for systemic therapy, is considered to be justified. 
The threshold of ≥25% scalp hair loss due to AA is also currently being used in the long-term 
safety study B7981032. While there is not a generally accepted definition of mild, moderate 
and severe AA, interviews of dermatologists and patients with an AA history of ≥50% scalp 
hair loss indicated that scalp hair loss >20% represents moderate to severe hair loss.(51) 
4.3. Justification for Dose 
This study will evaluate PF-06651600 administered at a dose of 200 mg QD for 4 weeks 
followed by a dose of 50 mg QD for up to 60 months for participants proceeding to TP3. 
This dose regimen was selected as it is the highest dose regimen being evaluated in the Phase 
3 development program in AA. 
Exposure margins of the proposed clinical doses relative to the nonclinical NOAEL 
exposures are summarized in Table 1. 
 
Table 1. 
PF-06651600 Exposure Margins and No Observed Adverse Effects 
Level 
 
Dose/Route 
Mean AUC in 
Dogs (unbound, 
ng•hr/mL) 
Mean Clinical 
AUC (unbound, 
ng•hr/mL) 
Calculated Safety 
Margin 
Safety Exposure Margins for Human 200 mg QD Dose in AA patients 
Dog 2-month 
toxicology (Study 1) 
NOAEL: 
45 mg/kg oral 
44100 
5310 
8.3 
Dog 9-month 
toxicology (Study 2) 
NOAEL: 
10 mg/kg oral 
7940 
5310 
1.5 
Safety Exposure Margins for Human 50 mg QD Dose in AA patients 
Dog 2-month 
toxicology (Study 1) 
NOAEL: 
45 mg/kg oral 
44100 
1070 
41 
Dog 9-month 
toxicology (Study 2) 
NOAEL: 
10 mg/kg oral 
7940 
1070 
7.4 
Abbreviations: AUC = area under the concentration-time curve; NOAEL = no observed adverse effect 
level; QD = once daily. 


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4.4. End of Study Definition 
A participant is considered to have completed the study: 
• If participant has completed all phases of TP1 & TP2, including follow-up visit and 
does not continue to TP3 due to local commercial availability of PF-06651600 for 
AA; OR 
• If participant has completed all phases of TP3, including Follow-up Visit; OR 
• If participant discontinued from the study during TP3 due to local commercial 
availability of PF 06651600 for AA. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
The primary completion date (PCD) is defined as the date when the last participant completes 
the Month 9 Visit of the Placebo-Controlled Phase. 
 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Type of Participant and Disease Characteristics 
1. Participants must meet the following AA criteria: 
• Have a clinical diagnosis of AA. Other etiologies of hair loss coexistent with AA 
are allowed. 
• ≥25% scalp hair loss due to AA (including AT and AU) measured by SALT at 
screening which, in the opinion of the investigator, is appropriate for systemic 
therapy. 
• Hair loss must be carefully reviewed to verify that ≥25% terminal scalp hair 
loss is due to AA (ie, SALT [AA] score is ≥25). If in cases of concomitant AA 
and other etiologies of alopecia, it cannot be verified that SALT (AA) score is 
≥25, then the participant must be excluded from the study. 


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Hearing and Neurological Assessments at Screening 
2. Participants must have normal hearing and BAEP assessed by the audiology 
professional and confirmed by the central reader. 
3. Participants must have a normal neurological examination by a neurologist and 
absence of peripheral neuropathy by history, symptoms, and the neuropathy 
assessment. Participants with stable unilateral carpal tunnel syndrome or stable 
unilateral ulnar entrapment on neurological examination or history are allowed in the 
study. 
Age 
4. All participants must be 18 to 50 years of age at the time they sign the informed 
consent. 
Sex 
5. Male or Female 
Contraceptive use by men or women should be consistent with local regulations regarding 
the methods of contraception for those participating in clinical studies. 
The study protocol requirements regarding contraception are as follows: 
a. Male participants: 
No contraceptive measures required. 
b. Female participants: 
• A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
• Is not a woman of childbearing potential (WOCBP), See Section 10.4. 
OR 
• Is a WOCBP and using a contraceptive method that is highly effective, with a failure 
rate of <1%, as described in Section 10.4 during the intervention period and for at 
least 28 days after the last dose of study intervention. The investigator should 
evaluate the effectiveness of the contraceptive method in relationship to the first dose 
of study intervention. 
• A WOCBP must have a negative highly sensitive (Section 10.2) pregnancy test (urine 
or serum as required by local regulations) at screening and at the Day 1 visit before 
the first dose of study intervention. 


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• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
participation if the serum pregnancy result is positive. 
• The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Informed Consent 
6. All participants must be capable of giving signed informed consent as described in 
Section 10.1 which includes compliance with the requirements and restrictions listed 
in the informed consent document (ICD) and in this protocol. 
7. All participants must be willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures. 
Prior/Concomitant Therapy 
8. If receiving permitted concomitant medications, participants should 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. Participants must be willing 
to stay on a stable regimen during the duration of the study (see Section 6.5). 
9. All participants 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. 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Other medical or psychiatric condition, including recent (within the past year) or 
active suicidal ideation or behavior, or laboratory abnormality that may increase the 
risk of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study. Any psychiatric condition including recent or active 
suicidal ideation or behavior that meets any of the following criteria: 
a. Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of the Columbia Suicide Severity Rating 
Scale (C-SSRS) (Section 8.2.11). 
b. Suicidal behavior in the past year: a “Yes” answer on any question in the suicidal 
behavior section of the C-SSRS. 
c. For participants who had previous history of suicidal behaviors in the past 
>1 year: (a “Yes” answer to any of the suicidal behavior items of the C-SSRS), a 
risk assessment must be performed and documented by a qualified mental health 


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professional to assess whether it is safe for the participant to participate in the 
trial. 
d. The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 
e. Clinically significant depression as indicated by a Patient Health 
Questionnaire-8 Items (PHQ-8) total score ≥15 (Section 8.2.12). 
NOTE: For any participant who has significant depression or any suicidal behavior, 
the participant will not be assigned to study intervention and should be referred for 
appropriate evaluation and treatment. 
2. Any current hearing loss or current disease that can affect hearing, including 
disorders associated with progressive hearing loss in adults, e.g. Meniere’s disease, 
otosclerosis, superior semicircular canal dehiscence or labyrinthitis. 
3. Occupational or recreational noise exposure sufficient to place the participant at risk 
for noise-induced hearing loss without proper ear protection as determined by the 
audiology professional performing the screening audiological evaluation. 
4. Current or history of clinically significant central or peripheral neurological disease 
regardless of etiology or any other neurologic disease that could impact study results 
in the judgement of the investigator or the examining neurologist. 
5. First degree family history of hereditary neuropathy. 
6. Any history of peripheral neuropathy (PN), including diabetic PN, chemotherapy- 
induced PN, drug-induced PN, genetic PN, idiopathic PN, etc. 
7. Cognitive or behavioral conditions which could prevent the participant from 
cooperating with the investigator or audiology/neurology professionals performing 
the evaluations or procedures. 
8. HbA1c ≥7.5% at screening. 
9. 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 (particularly thyroid 
disease and parathyroid disease, which can be associated with hair loss), pulmonary, 
cardiovascular, psychiatric, immunologic (other than AA), rheumatologic, 
dermatologic 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 study intervention administration, or interfere 
with the interpretation of study results; or in the opinion of the investigator or Pfizer 
(or designee), the participant is inappropriate for entry into this study, or 


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unwilling/unable to comply with study procedures (Section 8) and Lifestyle 
Considerations (Section 5.3). 
10. Any present malignancies or 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. 
11. 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. History of disseminated herpes zoster or disseminated herpes simplex, or recurrent 
(more than one episode of) localized, dermatomal herpes zoster. 
13. 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 criteria regarding Tuberculosis [TB] infection, see 
Exclusion Criterion 21). 
14. Known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency. 
15. History of human immunodeficiency virus (HIV) or positive serology for HIV) at 
screening. 
16. Significant trauma or major surgery within 1 month of the first dose of study 
intervention. 
17. Significant trauma, surgery, or clinical condition at the skin biopsy site(s) which 
could interfere with the collection or interpretation of the punch biopsy specimens. 
18. Considered in imminent need for surgery. Participants with elective surgery 
scheduled can only be enrolled with the approval of the sponsor. 
19. Active acute or chronic infection requiring treatment with oral antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1, or any 
active infection not meeting other exclusion criteria within 1 week prior to Day 1. 
NOTE: participants may be rescreened after the infection resolves. Long-term 
antibiotic treatment for acne is not exclusionary but should be approved by the 
Sponsor. 
20. Infection with hepatitis B or hepatitis C viruses according to protocol-specific testing 
algorithm. 
a. For hepatitis B, participants will undergo testing for hepatitis B surface antigen 
(HBsAg) and hepatitis B core antibody (HBcAb). Participants who are HBsAg 
positive will not be eligible for this study. Participants who are HBsAg negative 
but HBcAb positive will be reflex tested for hepatitis B surface antibody 
(HBsAb). Additional reflex testing for hepatitis B virus deoxyribonucleic acid 


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(HBVDNA) is also required for participants who are HBsAg negative and HBcAb 
positive in countries in which hepatitis B prevalence has been reported at a rate of 
>5.0% or if required by local standard of care. Please refer to Section 8.2.10.3 and 
Section 10.6 for testing algorithm, reflex testing, and full eligibility criteria. 
b. For hepatitis C, all participants will undergo testing for hepatitis C antibody 
(HCVAb) during screening. Participants who are HCVAb positive will be 
reflex-tested for hepatitis C ribonucleic acid (HCV RNA). Participants who are 
HCVAb and HCV RNA positive are not eligible for the study. 
21. Have evidence of untreated or inadequately treated active or latent Mycobacterium 
tuberculosis (TB) infection as evidenced by the following: 
a. A positive QuantiFERON® TB Gold In-Tube test (QFT-G) or positive or 
borderline T-SPOT®.TB (T-Spot test) performed within the 3 months prior to Day 
1 (Visit 2). If the laboratory reports the test as indeterminate, the test should be 
repeated. If the result of the repeat test is indeterminate, a purified protein 
derivative (PPD) test may be substituted for the QFT-G test or T-Spot test only 
with approval from the Pfizer Medical Monitor on a case-by-case basis. 
b. Chest radiograph (CXR) (posterior-anterior and lateral views are recommended; 
however local guidelines should be followed) (Section 8.2.3) or other appropriate 
diagnostic imaging such as computed tomography or magnetic resonance imaging 
(MRI) with changes suggestive of active TB infection within 3 months prior to 
Screening. Chest radiograph should be performed according to local standards of 
care or country specific guidelines. 
c. History of either untreated or inadequately treated latent or active TB infection. 
If a participant has previously received an adequate course of therapy for either 
latent (9 months of isoniazid (INH) in a locale where rates of primary multi-drug 
resistant TB infection are <5% or an acceptable alternative regimen) or active 
(acceptable multi-drug regimen) TB infection, neither a QFT-G test, a T-Spot test, 
nor a PPD test need be obtained. Details of the previous course of therapy 
(eg, medication(s) used, dose, duration of therapy) should be documented in the 
source documentation. 
A chest radiograph (ie, CXR or other appropriate diagnostic imaging such as 
computed tomography or MRI) must be obtained at screening if not done within 
the 3 months prior to screening (see Section 8.2.3). To be considered eligible for 
the study, the chest radiograph must be negative for active TB infection. 
A participant who is currently being treated for active or latent TB infection must 
be excluded from the study. 


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Prohibited Prior/Concomitant Therapy 
22. Receipt of (in the timeframes outlined below), or anticipated treatment with (during 
the course of the study), the following prohibited prior/concomitant medication(s) 
or treatment regimens (and those listed in Section 10.8): 
a. At any time: 
• Previous use of PF-06651600 in any disease indication. 
• Previous use of any non-B-cell selective lymphocyte-depleting agent (eg, 
alefacept, alemtuzumab). 
b. Within 6 months of first dose of study intervention or 5 half-lives (if known), or 
until lymphocyte count returns to normal, whichever is longer: any 
B-cell-depleting agents including, but not limited to, rituximab. 
c. Within 12 weeks of first dose of study intervention or 5 half-lives (if known), 
whichever is longer: 
• Any systemic JAK inhibitor for use in any disease indication. 
• Other immunomodulatory biologic agents. 
Note: Discontinuation of any JAK inhibitor due to a treatment-related safety event is 
exclusionary. Topical use of any JAK inhibitor during the course of the study is 
prohibited. 
d. Within 8 weeks of first dose of study intervention or within 5 half-lives (if 
known), whichever is longer: 
• Other systemic treatments that could be immunosuppressive including: 
• Cyclosporine A, azathioprine, methotrexate (MTX), 
mycophenolate mofetil (MMF), everolimus, ibrutinib. 
• Systemic (oral or injectable) corticosteroids. 
• Topical or intralesional corticosteroids in formulations/ 
doses/frequencies that, in the investigator’s judgement, could lead 
to substantial systemic exposures (except as described in 
Section 8.2.9.2.2). 
e. Vaccinated with a live attenuated vaccine (or exposed to a person vaccinated 
with a live attenuated vaccine) within the 6 weeks prior to the first dose of study 
intervention or is expected to be vaccinated or have household exposure to these 
vaccines during treatment or during the 6 weeks following discontinuation of 
study intervention. 


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f. Within 4 weeks of first dose of study intervention or 5 half-lives (if known), 
whichever is longer: prohibited moderate to potent CYP3A inducers as listed in 
Section 10.8. 
g. Within 1 week of first dose of study intervention or 5 half-lives (if known), 
whichever is longer: 
• Herbal medications with unknown properties. 
• Prohibited CYP3A substrates as described in Section 10.8. 
h. Medications that may be associated with peripheral neuropathy or hearing loss: 
• Chemotherapeutic agents or immunotherapy within 2 years before 
screening. 
• Aminoglycosides or 2nd line injectable anti-TB drugs within 6 months 
before screening. 
• Metronidazole or INH within 4 weeks before baseline. 
• Loop diuretics within 2 weeks before screening. 
• Quinine or quinidine within 1 week before screening. 
• Any radiation therapy to the lumbosacral plexus. 
• Current use of salicylates (other than low dose aspirin for prevention of 
cardiovascular / cerebrovascular disease). 
Prior/Concurrent Clinical Study Experience 
23. Participation in studies involving investigational products (eg, drugs or vaccines) 
within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to study 
entry and/or during study participation 
Diagnostic Assessments 
24. Abnormal findings on the screening chest radiographs (eg, chest x-ray) including, but 
not limited to, presence of active TB, infection, cardiomyopathy, or malignancy. 
NOTE: Chest radiograph examination may be performed up to 3 months prior to 
Screening visit. Documentation of the reading by a qualified radiologist or 
pulmonologist must be available in the source documentation. 


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25. ANY of the following conditions at screening: 
a. Screening 12-lead ECG that demonstrates: 
• Clinically significant abnormalities requiring treatment (eg, acute myocardial 
infarction, serious tachy- or brady-arrhythmias) or indicating serious 
underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson-White 
syndrome); 
• Confirmed QT corrected using Fridericia’s correction factor (QTcF) 
prolongation (>450 ms). 
b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of 
Torsades de Pointes. 
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 
appropriate: 
a. Absolute neutrophil count <1.2 × 109/L (<1200/mm3); 
b. Hemoglobin <11.0 g/dL or hematocrit <33%; 
c. Platelet count <150 × 109/L (<150,000/mm3); 
d. Absolute lymphocyte count of <0.8 × 109/L (<800/mm3); 
e. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 based on the 
Cockcroft-Gault formula adjusted for the body surface area; 
f. Enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
values >2 × upper limit of normal (ULN); 
g. Total bilirubin >1.5 × ULN; participants with Gilbert’s syndrome would be 
eligible for this study provided the direct bilirubin is ≤ULN; 
h. In the opinion of the investigator or Pfizer (or designee), have any clinically 
significant laboratory abnormality that could affect interpretation of study data or 
the participant’s participation in the study. 


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Other Exclusions 
27. Investigator site staff members or Pfizer employees directly involved in the conduct 
of the study, site staff members otherwise supervised by the investigator, and their 
respective family members. 
28. Have history of alcohol or substance abuse. 
29. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1. 
5.3. Lifestyle Considerations 
5.3.1. Contraception 
Participants who are WOCBP must agree to use one highly effective method of contraception 
(as specified in Section 10.4), as applicable. 
The investigator or his/her designee, in consultation with the participant, will confirm that the 
participant has selected an appropriate method of contraception for the individual participant 
from the permitted list of contraception methods (See Section 10.4), and will confirm that the 
participant has been instructed in its consistent and correct use. At time points indicated in 
the SoA (Section 1.3), the investigator or designee will inform the participant of the need to 
use highly effective contraception consistently and correctly and document the conversation 
and the participant’s affirmation in the participant’s chart (participants need to affirm their 
consistent and correct use of at least 1 of the selected methods of contraception). In addition, 
the investigator or designee will instruct the participant to call immediately if the selected 
contraception method is discontinued and document the requirement to use an alternate 
protocol-specified method, including if the participant will no longer use abstinence as the 
selected contraception method or if pregnancy is known or suspected in the participant or 
partner. The contraception check for WOCBP will be performed during each study visit and 
monthly between study visits at the time of the phone contact to check the at-home 
pregnancy test results (see Section 8.2.13). 
5.3.2. Meals and Dietary Restrictions 
On study visit days when lipid panel will be collected (see the SoA [Section 1.3]), 
participants must comply with fasting requirements for at least 8 hours prior to the visit. 
Water and permitted non-study medications are allowed (see Section 6.5.1). 
Participants must agree not to drink tonic water during the study. 
5.3.3. Caffeine and Tobacco 
Participants will abstain from using tobacco products or ingesting caffeine- or 
xanthine- containing products (eg, coffee, tea, cola drinks, and chocolate) for at least 
30 minutes before pulse rate and blood pressure measurements. 
5.3.4. Elective Surgery 
During the study, no elective surgery should occur without first consulting with the sponsor. 
Preferably, elective surgery should occur before the study or be delayed until participation in 


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the study is completed. Participants who require elective surgery should temporarily 
discontinue study intervention for one week prior to the surgical procedure and remain off 
study intervention after the surgical procedure until sutures/staples are removed. If absorbing 
sutures or chemical closure methods are utilized, study intervention can be resumed when the 
operative site is sufficiently healed, and risk of infection is minimal. Per Section 6.4, if the 
participant interrupts study intervention for >14 consecutive days, this must be discussed 
with the sponsor for possible withdrawal from the study. Refer to Section 6.5.4 for additional 
guidance regarding surgeries. 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
Screening laboratory tests with abnormal results may be repeated 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 participant may enter the 
study upon discussion with, and agreement by, the sponsor. 
Participants who do not meet the criteria for participation in this study (screen failure) may 
be rescreened (with a new screening number) following an agreement with the sponsor. 
6. STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol. 
6.1. Study Intervention(s) Administered 
In both the placebo-controlled phase (TP1) and active therapy extension phase (TP2), each 
participant will receive a total of 4 tablets QD during the initial 4-week period and a total of 1 
tablet QD during the remainder of that study phase. To maintain blinding, participants who 
received PF-06651600 during the placebo-controlled phase will receive 1 tablet QD of PF- 
06651600 and 3 tablets of placebo QD for a total of 4 tablets QD during the initial 4-week 
period of the active therapy extension phase. 


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Placebo-Controlled Phase (TP1) by Dose Period 
Arm Name 
PF-06651600 
Placebo 
Visits 2 – 3 
Visits 3 - 6 
Visits 2 – 3 
Visits 3 - 6 
PF-06651600 
200 mg QD (4- 
week dose) 
PF-06651600 50 
mg QD 
Placebo 
(4-week dose) 
Placebo 
Intervention 
Number 
PF-06651600 
PF-06651600 
Not applicable 
Not applicable 
Intervention 
Name 
Ritlecitinib 
Ritlecitinib 
Placebo 
Placebo 
Type 
Small molecule 
Small molecule 
Other 
Other 
Dosage Form 
Tablet 
Tablet 
Tablets 
Tablets 
Dose Strength 
50 mg 
50 mg 
0 mg 
0 mg 
Dosage 
50 mg – 4 tablets 
50 mg – 1 tablet 
0 mg -4 tablets 
0 mg -1 tablet 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Sourcing 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Packaging and 
Labeling 
Study Intervention 
will be provided in 
blister cards. Each 
blister card will be 
labeled as required 
per country 
requirement. 
Study Intervention 
will be provided in 
blister cards. Each 
blister card will be 
labeled as required 
per country 
requirement. 
Study Intervention 
will be provided in 
blister cards. Each 
blister card will be 
labeled as required 
per country 
requirement. 
Study Intervention 
will be provided in 
blister cards. Each 
blister card will be 
labeled as required 
per country 
requirement. 
 
 
Active Therapy Extension Phase (TP2) & Extension Phase (TP3) 
Initial 4-Weeks Dose (4 Tablets) 
50 mg QD Dose 
(1 Tablet/Capsule) 
(All Participants) 
Received Placebo in 
Placebo-Controlled Phase 
Received PF-06651600 in Placebo- 
Controlled Phase 
ARM Name 
PF-06651600 
200 mg QD 
PF-06551600 50 mg QD/Placebo 
PF-06551600 50 mg 
QD 
Intervention 
Number 
PF-06651600 
PF-06651600 
Not applicable 
PF-06651600 
Intervention 
Name 
Ritlecitinib 
Ritlecitinib 
Placebo 
Ritlecitinib 
Type 
Small molecule 
Small molecule 
Other 
Small molecule 
Dosage Form 
Tablet 
Tablet 
Tablet 
Tablet/Capsule 
Dose Strength 
50 mg 
50 mg 
0 mg 
50 mg 
Dosage 
50 mg – 4 tablets 
50 mg – 1 tablet 
0 mg - 3 
tablets 
50 mg – 1 tablet or 
capsule (TP3 only) 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Sourcing 
Provided centrally by the 
Sponsor 
Provided centrally 
by the Sponsor 
Provided 
centrally by 
the Sponsor 
Provided centrally 
by the Sponsor 
Packaging and 
Labeling 
Study Intervention will be 
provided in blister cards. 
Each blister card will be 
Study Intervention 
will be provided in 
blister cards. Each 
Study 
Intervention 
will be 
Study Intervention 
will be provided in 
blister cards or 


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Active Therapy Extension Phase (TP2) & Extension Phase (TP3) 
Initial 4-Weeks Dose (4 Tablets) 
50 mg QD Dose 
(1 Tablet/Capsule) 
(All Participants) 
Received Placebo in 
Placebo-Controlled Phase 
Received PF-06651600 in Placebo- 
Controlled Phase 
labeled as required per 
country requirement. 
blister card will be 
labeled as required 
per country 
requirement. 
provided in 
blister cards. 
Each blister 
card will be 
labeled as 
required per 
country 
requirement. 
bottles (TP3 only). 
Each blister 
card/bottle will be 
labeled as required 
per country 
requirement. 
Abbreviation: QD = once daily 
 
Participants will swallow the study intervention whole and will not manipulate or chew the 
study intervention prior to swallowing. 
6.2. Preparation/Handling/Storage/Accountability 
• The study intervention will be dispensed using an Interactive Response Technology 
(IRT) management system at each visit as specified in the SoA (Section 1.3). At the 
Month 1 visit, the participant will return the package containing the study 
intervention which was dispensed at the Day 1 visit for accountability. 
• A qualified staff member will dispense the study intervention via unique container 
numbers on the blister cards or bottles (TP3 only) provided. The participant should be 
instructed to maintain the product in the blister cards or bottles provided throughout 
the course of dosing and return the blister cards or bottles to the site at the next study 
visit. Site staff will instruct participants on the proper storage requirements for study 
intervention that is taken home. 
• The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. At a minimum, daily 
minimum and maximum temperatures for all site storage locations must be 
documented and available upon request. Data for nonworking days must indicate the 
minimum and maximum temperatures since previously documented for all site 
storage locations upon return to business. 
Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 


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actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP Manual. 
Study interventions should be stored in their original containers. 
Site staff will instruct participants on the proper storage requirements for take-home 
study intervention. 
The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records). such as the 
Investigational Product Accountability Log or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record. All study intervention that is taken home by the participant, both used 
and unused, must be returned to the investigator by the participant. Returned study 
intervention must not be redispensed to the participants. 
Further guidance and information for the final disposition of unused study 
interventions are provided in the IP Manual. All destruction must be adequately 
documented. 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. 
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP Manual. 
6.2.1. Preparation and Dispensing 
A qualified staff member will dispense the study intervention using the IRT system via 
unique container numbers in the blister cards, or bottles (TP3 only) provided, in quantities 
appropriate according to the SoA (Section 1.3). A second staff member will verify the 
dispensing. The participant should be instructed to maintain the product in the blister cards, 
or bottles (TP3 only) provided throughout the course of dosing and return the blister cards or 
bottles (TP3 only) to the site at the next study visit. 
At the EOP visit (Month 6 or Month 9/EOP, as appropriate), additional double-blind therapy 
may be dispensed if the neurological and/or audiological/BAEP assessments (including the 
central read confirmation and any repeat assessments if deemed necessary by the central 
reader) are not yet completed. Additional double-blind therapy would be dispensed as a 32- 
day supply, but dosing may not extend past the end of the +21 day EOP visit window. Once 
neurological and audiological/BAEP EOP assessments are complete, active-therapy may be 
dispensed either on site or by shipping to the study participant. 


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6.3. Measures to Minimize Bias: Randomization and Blinding 
 
Study using 
IVRS/IWRS 
All participants will be centrally assigned to randomized study intervention using an 
Interactive Voice/Web Response System (IVRS/IWRS). Before the study is 
initiated, the telephone number and call-in directions for the IVRS and/or the log in 
information & directions for the IWRS will be provided to each site. 
Study intervention will be dispensed at the study visits summarized in SoA 
(Section 1.3). 
Returned study intervention should not be re-dispensed to the participants. 
Blind Break 
(IVRS/IWRS) 
The IVRS/IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding 
of a participant’s treatment assignment is warranted. Participant safety must always 
be the first consideration in making such a determination. If the investigator decides 
that unblinding is warranted, the investigator should make every effort to contact the 
sponsor prior to unblinding a participant’s treatment assignment unless this could 
delay emergency treatment of the participant. If a participant’s treatment assignment 
is unblinded, the sponsor must be notified within 24 hours after breaking the blind. 
The date and reason that the blind was broken must be recorded in the source 
documentation and case report form, as applicable. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system. 
6.3.1. Blinding 
TP1 will be conducted in a double-blind manner. Participants, investigators, site and sponsor 
staff (except for the sponsor staff involved in the assignment or distribution of study 
intervention) will be fully blinded to the treatment assignments. 
After the PCD (Section 4.4) TP2 will be conducted in a single-blind manner. Participants, 
investigators and site staff will remain blinded, but the sponsor staff will be un-blinded to the 
initial treatment assignments, in order to conduct the analysis for the PCD-CSR 
(Section 9.4.1). Although participants, investigators, site and sponsor staff will all be aware 
that active therapy will be provided to all participants in TP2 (and that after the first 4 weeks 
of TP2 all participants will be receiving the same dose of active treatment), study 
intervention packaging will remain blinded during this period. 
After all participants have completed TP2, the study will be fully unblinded to the initial 
treatment assignments. 
6.4. Study Intervention Compliance 
Participant compliance with study intervention will be assessed at each visit during the 
Intervention Period. Compliance with the dosing of study intervention will be verified by 
delegated site personnel through a combination of counting returned tablets, or capsules (TP3 
only) and discussion with the participant, which will be documented in the source 
documents. Deviation(s) from the prescribed dosage regimen should be recorded in the 


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electronic Case Report Form (eCRF). When study intervention is administered at the clinic, it 
will be administered by the appropriately designated staff at the investigator site. 
Participants should take the tablets, or capsules (TP3 only), orally according to the dosing 
instructions provided with the study intervention. Participants will be encouraged to take the 
study intervention in the morning whenever possible. Participants should take the study 
intervention at approximately the same time every day. However, for study visit days, 
participants 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 <8 hours, the missed dose should not 
be administered. If a dose is missed and the interval to the next dose is ≥8 hours, the missed 
dose should be administered. 
The study intervention may be temporarily withheld for a maximum of 14 consecutive days 
at the discretion of the investigator. Participants interrupting study intervention for 
>14 consecutive days for any reason must be discussed with the sponsor for possible 
withdrawal from the study. For participants who are considering elective surgery refer to 
Section 5.3.4 regarding information on temporary withholding of study intervention for 
elective surgery. 
If compliance is <80%, the investigator or designee is to counsel the participant and ensure 
steps are taken to improve compliance. If the participant is over-compliant (>120%) with 
study intervention (intentional or accidental), the investigator or designee is to counsel the 
participant and ensure correct understanding of the study intervention dosing regimen. The 
investigator should contact the Pfizer Study Clinician promptly with any over-compliance 
that may potentially impact the safe use of study intervention or that may result in a SAE. 
6.5. Concomitant Therapy 
Medications/treatments that are taken in the screening period (after informed consent is 
obtained and before the first dose of study intervention) as well as any 
medications/treatments taken for the treatment of AA at any time prior to the screening visit 
will be documented as prior medications/treatments. Medications/treatments taken after the 
first dose of study intervention has been administered will be documented as concomitant 
medications/treatments. 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant is receiving at the time of enrollment or 
receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 


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6.5.1. Permitted Concomitant Medications 
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). With the exception of medications prohibited for use in 
Section 5.2, CYP3A inhibitors are permitted to be used during the study. Sensitive and 
moderate sensitive CYP3A substrates permitted to be used during the study are listed in 
Section 10.8. 
A participant 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 on the case report form (CRF). Acetaminophen/paracetamol is allowed if dosed 
no more than 3.0 g/day for no more than 5 consecutive days. Participants are not allowed any 
other investigational drugs or treatments during the study. 
Participants 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. 
Participants 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 
participant’s record and CRF. 
Unless a prohibited medication or treatment, participants 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. 
6.5.2. Prohibited Concomitant Medications 
Participants will abstain from all prohibited medications as described in Section 5.2 and 
Section 10.8. Medically necessary medications should not be discontinued without prior 
evaluation of acceptable alternatives, including consultation with prescribing health 
professional. 
Participants should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications. 
All medications and treatments that could affect AA must be discontinued. During the 
study, if it is discovered that a subject has been taking a medication or treatment that could 
affect AA, the investigator should contact the Sponsor for each case to determine whether the 
subject must be discontinued. 
Participants 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. 


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6.5.3. Vaccinations 
Vaccination with a live attenuated vaccine is prohibited within the 6 weeks prior to the first 
dose of study intervention, during the study, and for 6 weeks following discontinuation of 
study drug. Vaccines (including COVID-19 vaccines) that are not live attenuated are 
permitted. 
Similarly, current routine household contact with individuals who have been vaccinated with 
live attenuated vaccine must be avoided during study treatment and for 6 weeks following 
completion of study treatment. Following vaccination with live attenuated vaccine, the virus 
may be shed in bodily fluids, including stool, and there is a potential risk that the virus may 
be transmitted. 
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, vaccinia (smallpox) 
vaccine, and Zostavax (zoster vaccine live). 
6.5.4. Surgery 
During the study, no elective surgery should occur without first consulting with the Pfizer 
Medical Monitor or designee. Preferably, elective surgery should occur before the study or 
be delayed until participation in the study is completed. Refer to Section 5.3.4 for guidelines 
regarding temporary withholding of study intervention prior to and after elective surgery. 
The Pfizer Medical Monitor or designee should be notified if a participant requires surgery 
(including dental surgery) during the study to determine whether the participant should 
discontinue from the study and/or discontinue study intervention prior to the surgical 
procedure. The Pfizer Medical Monitor or designee should be notified as soon as possible if a 
participant undergoes a surgical procedure without first informing the study staff. 
6.6. Dose Modification 
Dose modification of the study intervention is not permitted in this study. For information on 
temporary withholding of study intervention (see Section 6.4). 
6.7. Intervention after the End of the Study 
There is no intervention required by the protocol following the end of the study. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
7.1.1. Permanent discontinuation 
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (ie, definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: treatment-related SAEs, serious infections, and other 
events as described in Section 10.7.2. 


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Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for the assessments at the Early Termination (ET) and Follow-up visits (per the 
SoA [Section 1.3]). See the SoA (Section 1.3) for data to be collected at the time of 
discontinuation of study intervention and follow-up and for any further evaluations that need 
to be completed. 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
Refer to Section 10.7 for discontinuation criteria. 
7.1.1.1. Observation Period 
Participants will be asked to remain in the study after the Follow-up visit without study 
intervention. The Period during which participants are in the study after having permanently 
discontinued study intervention is referred to as the Observation Period. During this period 
participants will continue to comply with study visit schedules for approximately 2 years or 
until study end, whichever occurs first. At visits during the Observation Period, only the 
SALT, PGI-C, and concomitant medications/treatments will be collected at the visits 
specified in the applicable SoAs in Section 1.3.2; AE and SAE reporting will follow the 
guidelines in Section 8.3. 
Participants will complete the final visit in the Observation Period approximately 2 years 
after the last dose of study intervention or at study end whichever occurs first as follows: 
• at the protocol-scheduled visit 24 months after the last dose of study intervention, OR 
• at the next scheduled visit after the 24-month time point (if no scheduled visit falls 
at the 24-month time point), OR 
• at study end. 
For example, if the last dose of study intervention occurs around the time of Month 22E then 
the final visit in the Observation Period would be conducted at Month 51E (ie, the next 
closest scheduled visit occurring 24 months after Month 22). 
7.1.2. Temporary Discontinuation 
See Section 5.3.4 and Section 6.4. 
7.2. Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following: 
• Refused further follow-up; 


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• Lost to follow-up; 
• Death; 
• Study terminated by sponsor; 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA (Section 1.3) for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal. 
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
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. 
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved. 
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law. 
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 


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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA (Section 1.3). 
Protocol waivers or exemptions are not allowed. 
• 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study 
intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• 
Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICD may be utilized for screening 
or baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA (Section 1.3). 
• 
Participants will have up to 35 days of a screening period prior to the first dose of 
study intervention to confirm that they meet the participant selection criteria for the 
study. 
• 
The investigator (or appropriate delegate at the investigator site) must obtain a 
signed and dated ICD before performing any study-specific procedures. The ICD is 
signed and dated by each participant in accordance with the procedures described in 
Section 10.1.3. 
• 
Due to audiological and neurologic evaluations and possible need for tuberculin 
testing and chest radiograph, screening procedures may be performed over more 
than 1 visit within the 35 days prior to the Day 1 visit. 


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• 
To assure consistency and reduce variability, visits should occur at approximately 
the same time of day throughout the study. Participants should be encouraged to 
attend visits in the morning and prior to the participant’s dosing of study 
intervention as participants will receive their dose at the clinic during their study 
visit. 
• 
Urine pregnancy test must be performed at each visit (and must be negative) prior to 
dosing with the study intervention for female participants of childbearing potential 
through follow-up (see Section 10.4 and Section 8.2.13). 
• 
The patient-reported outcome assessment should be completed before the other 
evaluations or treatments at all of the visits (when patient reported outcome 
assessments are to be administered) when possible. Vital signs and ECGs should be 
performed before any laboratory blood collection. All other evaluations (unless 
noted otherwise) do not need to be performed in any specific order. 
• 
Participants are required to fast for at least 8 hours prior to all visits that include 
fasting lipid profile panel testing. During the fasting period, participants should 
refrain from all food and liquids (water and medications other than study 
intervention are permitted). 
• 
Every effort should be made to ensure that protocol-required tests and procedures 
are completed as described. However, it is anticipated that from time to time there 
may be circumstances outside the control of the investigator that may make it 
unfeasible to perform the test. In these cases, the investigator must take all steps 
necessary to ensure the safety and well-being of the participant. When a 
protocol-required test cannot be performed, the investigator will document the 
reason for the missed test and any corrective and preventive actions that he or she 
has taken to ensure that required processes are adhered to as soon as possible. The 
study team must be informed of these incidents in a timely manner. 
• 
For samples being collected and shipped, detailed collection, processing, storage, 
and shipment instructions and contact information will be provided to the 
investigator site prior to initiation of the study. 
• 
The total amount of blood collected from each participant over the duration of TP1 
plus TP2, including all assessments at the screening and follow-up visits (for 
participants not proceeding to TP3), will be approximately 200 mL. The maximum 
amount of blood collected from each participant over the duration of TP3, including 
all assessments at the follow-up visits, will be approximately 118 mL. The 
maximum amount of blood collected from each participant over the duration of the 
5-year study, including all assessments at the screening and follow-up visits, will be 
approximately 318 mL Repeat or unscheduled samples may be taken for safety 
reasons or for technical issues with the samples provided the total volume taken 
during the study does not exceed 550 mL during any period of 60 consecutive days. 


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• 
Refer to Section 10.7 for guidelines on participant safety monitoring and 
discontinuation. 
8.1. Efficacy Assessments 
8.1.1. Rater Qualifications 
Diagnosis of AA must be performed by a qualified dermatologist (board certified or 
equivalent) who has experience with AA. An experienced and qualified physician or 
healthcare professional may be permitted to perform the clinical evaluations of alopecia (ie, 
SALT). For all assessments, the rater must be formally delegated to perform this assessment 
by the PI and receive training (with proper documentation) on the protocol and applicable 
assessment scales prior to performing these evaluations. 
To assure consistency and reduce variability, the same rater should assess dermatological 
clinical evaluations for a given procedure and for an individual participant throughout the 
study (eg, one rater performs all SALT evaluations throughout the study). A back-up 
experienced and qualified, protocol-trained rater will only be allowed in special situations 
when the designated rater is unable to perform the evaluation. Use of the back-up rater will 
be documented. 
8.1.2. Clinical Assessments 
8.1.2.1. Severity of Alopecia Tool (SALT) 
SALT is a quantitative assessment of AA severity based on scalp terminal hair loss.(52) Scalp 
hair loss due to AA (AA SALT score) is measured at screening. The overall SALT score, 
which does not distinguish the reason for hair loss, will be collected at visits shown in the 
SoA (Section 1.3). 
Score parameters utilize 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, respectively. 
Hair prosthetics (eg, wigs, hair extensions) must be removed for clinical assessments of AA 
at all study visits. 
8.1.2.1.1. Non-AA SALT Score 
In addition to the overall amount of scalp terminal hair loss, scalp hair loss due to etiologies 
other than AA will be assessed using the SALT tool. This will only be collected for 
participants known to have scalp hair loss due to other etiologies in addition to AA. The non- 
AA SALT score will be collected at visits shown in the SoA (Section 1.3). 
8.1.2.1.2. Alopecia Areata Eligibility Assessment 
In addition to the overall amount of scalp terminal hair loss (overall SALT), scalp hair loss 
due to AA (AA SALT) will be assessed at the screening visit to verify eligibility of 
participants. 


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8.1.3. Patient Reported Outcomes 
8.1.3.1. Patient’s Global Impression of Change (PGI-C) 
The PGI-C asks the participant to evaluate the improvement or worsening of their AA as 
compared to the start of the study using a single-item, “Since the start of the study, my 
alopecia areata has: …”. The participants will select one of seven responses ranging from 
“greatly improved” to “greatly worsened”. 
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. Unscheduled visits, physical exams, or other study 
assessments may also be conducted at any time during the study to assess perceived safety 
issues. 
Safety monitoring and discontinuation criteria are provided in Section 10.7. 
For the purposes of safety monitoring and discontinuation, baseline values will be defined as 
follows: 
• 
Baseline values will be defined as the last non-missing values collected before dosing on 
Day 1 for all participants. 
8.2.1. Medical History, Physical Examinations, Height and Weight 
• 
Complete AA disease history includes collection of details of AA at screening: AA 
history, AA diagnosis, number of years of current episode of hair loss, pattern of 
scalp hair loss, body hair loss, the use of topical treatments, systemic treatments and 
other treatments for AA. 
Note: Initiation of the current episode should be the last occurrence when the patient 
had substantial scalp hair (regardless of whether that hair growth occurred 
spontaneously or was the result of interventional treatment) prior to scalp hair loss. 
• 
Medical history, including, but not limited to, comorbid conditions, history of drug, 
alcohol, tobacco use, dermatologic, auditory, and neurologic history, and infection 
history will be collected at screening and/or Day 1 (as applicable per the SoA 
[Section 1.3]) Refer to the CRF completion guidelines for specific information 
regarding medical history information to be collected for each group of participants. 
• 
Smoking status and average weekly alcohol consumption (units/week) will also be 
collected for all participants. 
• 
Height and weight will be measured without the participant wearing shoes or 
outerwear. Height (in or cm) and weight (lb or kg) will be measured and recorded in 
the source document at various time points according to the SoA (Section 1.3). 


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• 
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; abdomen; extremities; 
neurologic and auditory function; back; and lymph nodes. In addition, 
dermatological full body exam must be performed by the investigator, sub- 
investigator, or a qualified health professional per local guidelines. Dermatological 
examinations should also 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, neurologic and auditory function, and 
examination of body systems where there are symptom complaints by the 
participant. 
• 
When dermatologic adverse events are identified on physical exam, additional 
procedures may be required. Please refer to Section 8.2.9.2 for additional details. 
8.2.2. Vital Signs 
• 
Oral, tympanic, or axillary temperature, pulse rate, respiratory rate, and blood 
pressure will be assessed. It is preferred that body temperature be collected using the 
tympanic or oral methods; however, the axillary method is also permitted. The same 
method should be used consistently throughout the study. Vital signs should be 
performed before laboratory blood collection and ECG. 
• 
Blood pressure (BP) and pulse measurements will be assessed 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) with a completely automated device. Manual 
techniques will be used only if an automated device is not available. 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 participant 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 
BP cuff should be used to measure BP each time. 
• 
Pulse rate should be measured at approximately the same time as BP for a minimum 
of 30 seconds. 
• 
BP and pulse measurements should be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (eg, television, cell phones). 


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• 
Participants should refrain from smoking or ingesting caffeine during the 
30 minutes preceding the measurements. 
8.2.3. Chest Radiography 
CXR (posterior-anterior and lateral views are recommended; however local guidelines should 
be followed) or other appropriate diagnostic image (ie, computed tomography or MRI) must 
be taken at screening or within 3 months prior to screening visit for all participants. The chest 
radiograph must be read by a qualified radiologist or pulmonologist prior to the Day 1 visit 
for confirmation of eligibility per Section 5.2. Documentation of the reading by the qualified 
radiologist or pulmonologist must available in the source documentation. 
8.2.4. Electrocardiograms 
• 
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, 
QT, and QTcF intervals (or using an ECG machine which does not automatically 
calculate QTcF intervals, with the site’s qualified medical personnel performing the 
calculation with the QTcF calculator provided by the sponsor). Refer to Section 10.7 
for QTcF withdrawal criteria and any additional QTcF readings that may be 
necessary. 
• 
ECG should be performed before laboratory blood collection. 
• 
All scheduled ECGs should be performed after the participant has rested quietly for 
at least 10 minutes in a supine position and prior to any blood collection. 
• 
A paper or digital copy of the ECG should be filed in the participant’s chart and 
must be available to the sponsor upon request. 
• 
To ensure safety of the participants, qualified medical personnel will review all 
ECGs and make comparisons to the baseline measurements as defined in 
Section 8.2. 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. 
• 
ECG values of potential clinical concern are listed in Section 10.7. 
8.2.5. Neurological Examination 
Neurological examination must be performed by a qualified (board certified or equivalent) 
neurologist and will include a general neurological evaluation and a neuropathy assessment. 
The neuropathy assessment will assess for symptoms and signs of neuropathy. Refer to the 
Manuals for General Neurological and Neuropathy Assessments for additional details. 
The neurologist may recommend additional evaluations and / or additional visits. They may 
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Additionally, at any time, participants with clinically meaningful changes from baseline in 
neurologic signs or symptoms should be documented in the CRF, and the monitor and 
sponsor study clinician should be notified. 
The same neurologist should perform examinations on individual participants throughout the 
study, including during TP3 if a neurological evaluation by a neurologist is clinically 
indicated by the investigator. 
See Section 10.7 for follow-up assessment of participants who discontinue due to a 
neurological AE. 
8.2.6. Audiological Evaluations 
All participants will have an audiological evaluation at times specified in the SoA 
(Section 1.3). When possible, the participant should have the evaluation performed by the 
same audiology professional, at the same evaluation center using the same equipment during 
the study. 
In countries where licensed and certified audiologists are available, they are the 
recommended specialists for study-related audiometric testing and its clinical interpretation. 
In those countries in which an audiologist is not a licensed and certified specialty to interpret 
and manage audiometric test results, clinical interpretation should be performed by an 
appropriate specialist licensed and certified to interpret and manage audiometric test results 
(eg, otolaryngologist), while the actual audiometric testing procedure can be performed by a 
trained technician or equivalent who is able to perform all required tests. 
Participants must have a full audiological assessment completed during screening prior to 
Day 1. Audiology and BAEP evaluations should be done on the same day, with audiology 
assessment first. If they cannot be done on the same day, assessments must be within 7 days 
of each other. This evaluation includes audiological history, otoscopic examination, pure tone 
audiometry (air and bone conduction), speech audiometry, and immittance audiometry. All 
screening audiological evaluation results must be available prior to Day 1 to assess eligibility 
for all participants. 
At subsequent visits, the audiological assessments will be repeated including updated 
audiological history, otoscopic examination, pure tone audiometry, speech audiometry, and 
immittance audiometry for all participants; based upon results, additional audiological 
assessments may be required. 
For participants who terminate early from the study, the audiological evaluation should be 
performed. 
If there is a clinically meaningful, treatment-emergent decline in auditory function from the 
screening measurements, the participant must be promptly evaluated by an audiology 
professional to assess for possible causes. Evaluation results should then be discussed with 
the sponsor to determine if the participant should be discontinued from the study. 
Discontinued participants must be followed up off-treatment with appropriate testing at 


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regular intervals, until hearing recovers or is determined to be clinically stable. See 
Section 10.7 for follow-up assessment of participants who discontinue due to an auditory 
event. 
The central reader will review the audiology results for each applicable visit. 
Refer to the most current version of the Audiology Study Guide for details on audiological 
evaluation. 
8.2.7. Brainstem Auditory Evoked Potential Evaluations 
All participants will have a BAEP evaluation, as specified in the Manual for BAEP 
Evaluation, at the times specified in the SoA (Section 1.3). When possible, the participant 
should have the evaluations performed at the same evaluation center, by the same audiology 
professional using the same equipment, during the study. Audiology and BAEP evaluations 
should be done on the same day, with audiology assessment first. If they cannot be done on 
the same day, assessments must be within 7 days of each other. 
A central reader will be used for BAEP to confirm that locally read BAEP waves were 
labelled appropriately and at their peak so that latency and amplitude data are accurate. 
Central reading will also ensure consistency in BAEP interpretation. The BAEP recording 
may be repeated (including additional recordings with modified parameters) or the original 
recording may be reassessed based on feedback from the central reader. Only results 
confirmed by the central reader as accurately interpreted will be used for analysis. 
For participants who terminate early from the study, the BAEP evaluation should be 
performed. 
For follow-up assessment of participants who discontinue due to an auditory adverse event 
see Section 10.7. 
Refer to the most current version of the Manual for BAEP Evaluation for details on BAEP 
evaluation. 
8.2.8. Skin Punch Biopsy, Evaluation of IENFD and Axonal Dystrophy 
8.2.8.1. Skin Punch Biopsy 
All participants will have skin punch biopsies performed at times specified in the SoA 
(Section 1.3). The participant should have the biopsies performed at the same center during 
the study. 
Refer to the most current version of the Central Laboratory Manual for details on the skin 
punch biopsy procedure. 
See Section 10.7 for follow-up assessment of participants who discontinue due to a 
neurological adverse event. 


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8.2.8.2. Histology for Axonal Dystrophy and IENFD 
This will be performed by a central reader. 
8.2.9. Special Safety Assessment 
8.2.9.1. Suspected Opportunistic Infections 
In the event of a suspected opportunistic infection, every effort should be made to identify 
the pathogen utilizing laboratory or other methods appropriate to the clinical situation. 
8.2.9.2. Dermatological Events 
All participants will have a dermatological full body exam as noted in the SoA (Section 1.3). 
Guidelines for the assessment of herpetiform rash and drug-related rash are noted in 
Section 8.2.9.2.1 and Section 8.2.9.2.2, respectively. 
8.2.9.2.1. Herpetiform Rash 
For any occurrence of a suspected herpetiform rash (eg, herpes zoster or herpes simplex) or 
eczema herpeticum, specimens for viral DNA analysis will be obtained: a swab of the 
affected area will be collected for confirmation. Details for this collection will be provided in 
the laboratory manual. 
8.2.9.2.2. 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 participants reporting an unexplained skin rash should undergo a formal comprehensive 
dermatologic evaluation. In addition, the participant will be asked to rate the severity of 
pruritus within the last 24 hours on a scale from 0 (No itching) to 10 (Worst possible itching). 
A 4 mm punch biopsy will be taken unless there is a clear, non-drug related etiology (eg, 
infection, including herpes virus, 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 participant refuses 
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. 
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. 
Photographs of the rash will be taken when possible. Detailed procedures to assure 
photographic quality and consistency will be provided separately in a photography 
instruction manual. 


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Within 30 days of receipt, the principal investigator (PI) should forward all de-identified 
biopsy results, culture results, photographs, and any additional relevant test results to the 
sponsor for review. Refer to the Canfield Photography User Manual for details. 
8.2.10. Clinical Safety Laboratory Assessments 
• 
See Section 10.2 for the list of clinical laboratory tests to be performed and to the 
SoA (Section 1.3) for the timing and frequency. 
• 
Participants must abstain from all food and drink (except water and non-study 
medications) for a minimum of 8 hours prior to fasting lipid profile panel collection 
according to the SoA (Section 1.3). All other labs do not require fasting. 
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE section 
of the CRF. The laboratory reports must be filed with the source documents. 
Clinically significant abnormal laboratory findings are those which are not 
associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days of the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
o If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor 
notified. 
o All protocol-required laboratory assessments, as defined in Section 10.2 must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
Unscheduled clinical laboratory measurements may be obtained at any time 
during the study to assess any perceived safety issues. 
o If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s local laboratory require a change in participant 
management or are considered clinically significant by the investigator (eg, SAE 
or AE or dose modification), then the results must be recorded in the CRF. 
• See Section 10.5 for suggested actions and follow-up assessments in the event of 
potential drug-induced liver injury. 
8.2.10.1. Tuberculosis Testing 
QuantiFERON-TB Gold In-Tube (QFT-G) test is the preferred testing method; however, 
the T-SPOT.TB (T-Spot) test is also permitted when QFT-G is not available. 
The QFT-G test is an in vitro diagnostic test using a peptide cocktail simulating early 
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(CFP-10), and TB 7.7 proteins to stimulate cells in heparinized whole blood. Detection of 
interferon-gamma by Enzyme-Linked Immunosorbent Assay (ELISA) is used to identify in 
vitro responses to these peptide antigens that are associated with M. tuberculosis infection. 
The T-Spot test is also an in vitro diagnostic test; however, it differs in that it uses a peptide 
cocktail simulating ESAT-6 and CFP-10 proteins to stimulate peripheral blood mononuclear 
cells. Both the QFT-G test and the T-Spot test are indirect tests for M. tuberculosis infection 
(including disease) and are intended for use in conjunction with risk assessment, radiography, 
and other medical and diagnostic evaluations. 
A blood sample will be collected for either the QFT-G or the T-Spot testing. The site must 
determine which test will be performed as sample collection and processing guidelines differ. 
QFT-G testing will be performed at the central laboratory and T-Spot testing will be 
performed at the site’s local laboratory. Following QFT-G sample processing, the sample 
will be shipped to the central laboratory for testing. The procedure for processing and 
preparing the sample for shipment is described fully in the laboratory manual, which will be 
provided to investigators. 
In addition to TB testing as specified in this clinical protocol, a CXR will be performed as 
described in Section 8.2.3. 
8.2.10.1.1. Purified Protein Derivative (PPD) Test 
If the QFT-G test or T-Spot test cannot be performed, or if the results from the reference 
laboratory are indeterminate, then participants may be screened using the PPD Tuberculin 
Test (Mantoux method), with the approval of the Pfizer Medical Monitor. 
Participants must have the PPD test administered and evaluated by a health care professional 
48 to 72 hours later in order to be eligible for the study, unless performed and documented 
within the last 12 weeks. The test should be performed and interpreted as negative if 
induration is <5 mm. 
8.2.10.1.2. Screening Tuberculosis Testing 
During the screening period, it must be determined and documented that participants do not 
have evidence of untreated or inadequately treated active or latent infection with TB per 
Exclusion criteria 21 in Section 5.2. The results of TB screening conducted within 3 months 
prior to Day 1 visit or during the screening period must be documented in study records prior 
to Day 1 (Visit 2). 
8.2.10.1.3. Subsequent Tuberculosis Testing 
Subsequent (post-screening) TB testing will be conducted at the time points indicated in the 
SoA (Section 1.3) for all participants as described below. 
For participants with a negative QFT-G (or T-Spot or PPD) result during prior testing and no 
history of previous treatment for active or latent TB, the following testing will be conducted: 


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• QFT-G test or T-Spot test per Section 8.2.10.1. If the laboratory reports the test as 
indeterminate, the test should be repeated. If the result of the repeat test is 
indeterminate, a purified protein derivative (PPD) test may be substituted for the 
QFT-G test or T-Spot test only with approval from the Pfizer Medical Monitor on a 
case-by-case basis. 
• Participants with a positive result must have a chest radiograph or other appropriate 
diagnostic image (ie, computed tomography or MRI) performed. The chest 
radiograph must be read by a qualified radiologist or pulmonologist. 
• Participants with a positive result must have study intervention temporarily withheld 
until the decision to restart treatment has been discussed and agreed with the sponsor, 
prior to restarting treatment. For this to happen, the participant must be evaluated, and 
the test result must be reviewed by a specialist (eg, pulmonologist or infectious 
disease specialist) to determine if the participant has active or latent TB. Participants 
with active or latent TB must be discontinued. If it is determined by a specialist (eg, 
pulmonologist or infectious disease specialist) that the participant does not have 
active or latent TB, the decision to restart treatment must be approved by Pfizer. 
• Participants with a negative laboratory result may continue in the study and do not 
require a chest radiograph. 
For participants with a history of adequate previous treatment for active or latent TB, the 
following testing will be conducted: 
• Neither a QFT-G test, T-Spot test, nor a PPD test need be obtained. 
• CXR or other appropriate diagnostic image (ie, computed tomography or MRI) must 
be performed. The chest radiograph must be read by a qualified radiologist or 
pulmonologist. 
• Participants identified as having active TB must be discontinued from the study and 
referred to a specialist (eg, pulmonologist or infectious disease specialist) for 
evaluation. 
• Participants with a CXR or other appropriate diagnostic image (ie, computed 
tomography or MRI) negative for active TB may continue in the study. 
8.2.10.2. Day 1 Viral Screen 
A serum sample will be collected at Day 1 and submitted to the central lab for all 
participants. The sample will be stored and analyzed at a later date only at the sponsor’s 
request. In certain cases of suspected viral infection (eg, disseminated herpes zoster or 
varicella), the sponsor may request to analyze the sample to determine if the participant had 
exposure to that virus. Additional sample collection instructions and details regarding sample 
destruction will be provided in the lab manual. The retained samples will be destroyed upon 
participant completion of this study. 


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8.2.10.3. Hepatitis B Virus DNA (HBVDNA) Testing 
For participants in countries in which hepatitis B prevalence has been reported at a rate of 
>5.0%(53) or if required by local standard of care, HBVDNA testing will be performed as 
reflex testing for any participant who is positive for HBcAb at screening. In addition, 
HBVDNA testing will be performed according to the SoA (Section 1.3) for subjects who 
were enrolled with a positive HBcAb and a negative HBsAg in those regions for which 
hepatitis B prevalence has been reported at a rate of >5.0% or if required by local standard of 
care. Testing at additional time points may be performed as per the local standard of care. 
Please refer to Section 10.6 for the testing algorithm, reflex testing, and eligibility criteria. 
8.2.11. Suicidal Ideation and Behavior Risk Monitoring 
8.2.11.1. Columbia Suicide Severity Rating Scale (C-SSRS) 
There are 2 versions of the C-SSRS to be utilized in this study - “C-SSRS for screening and 
Day 1 visits” and “C-SSRS for any visits after Day 1”(54). The version used is dictated by the 
actual study visit and the participant population (See the SoA [Section 1.3]). 
At the screening or Day 1 visits, if the participant has had suicidal ideation associated with 
actual intent and a method or plan in the past year (“yes” answers on items 4, 5), the 
participant will not be included in the study. For participants, suicidal behavior in the past 
year (“Yes” answer on any question in the suicidal behavior section of the C-SSRS), is 
exclusionary. For participants who have had previous history of suicidal behaviors in the past 
>1 year, (a “Yes” answer to any of the suicidal behavior items of the C-SSRS), a risk 
assessment must be performed and documented by a qualified mental health professional to 
assess whether it is safe for the participant to participate in the trial. 
Any participants who are not eligible due to suicidal ideation or behavior should be referred 
for appropriate evaluation and treatment. 
For all participants with suicidal ideation associated with actual intent and a method or plan 
in the past year: At any visits after Day 1, if there are “yes” answers on items 4, 5, or on any 
question in the suicidal behavior section of the C-SSRS, the participant will be discontinued 
from the study and referred to a mental health professional for appropriate evaluation and 
treatment or immediately referred to the Emergency Room at the investigator’s judgement. 
8.2.12. Patient Health Questionnaire – 8 Items (PHQ-8) 
The Patient Health Questionnaire – 8 items (PHQ-8) is a patient reported questionnaire that 
consists of 8 items to assess participant depression level.(55) Individuals with clinically 
significant depression as noted by a PHQ-8 total score ≥15 at screening must not be enrolled 
in the study. 
8.2.13. Pregnancy Testing 
Pregnancy tests may be urine or serum tests but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA 
(Section 1.3). Following a negative pregnancy test result at screening, appropriate 


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contraception must be commenced, and a second negative pregnancy test result will be 
required at the baseline visit prior to the participant’s receiving the study intervention. 
In addition to pregnancy tests performed at the site, site personnel will instruct applicable 
participants to complete monthly urine pregnancy tests between study visits starting after the 
Month 1 visit through the Month 51E/EOT visit. The pregnancy testing between visits may 
occur outside of the study site. Urine pregnancy kits will be provided to participants at each 
study visit (starting at Month 1) and site personnel will instruct participants on when and how 
to administer the pregnancy test and how to interpret the result. The participants will be given 
enough kits to cover the monthly testing between visits (for example, at least 2 kits should be 
given at the Month 3 visit). Site personnel will be required to document the discussion, 
including confirmation of participant willingness to perform administered urine pregnancy 
test, and understanding of how to perform the test as well as how to interpret the test result. 
In addition, site personnel will contact participants between study visits to obtain monthly 
pregnancy test result and ensure this contact and the result of the pregnancy test are recorded 
in participant source documentation and the CRF. 
Pregnancy tests will also be done whenever 1 menstrual cycle is missed during the active 
treatment period (or when potential pregnancy is otherwise suspected) and at the end of the 
study. Pregnancy tests may also be repeated if requested by institutional review boards 
(IRBs)/ethics committees (ECs) or if required by local regulations. If a urine test cannot be 
confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such 
cases, the participant must be excluded if the serum pregnancy result is positive. In the case 
of a positive confirmed pregnancy, the participant will be withdrawn from administration of 
study intervention but may remain in the study for follow-up. 
8.2.14. Rater Qualifications 
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study. The minimum qualifications a rater must meet for each study rating 
assessment will be outlined in the Rater Assessment Manual provided to each participating 
site. The level of experience with the target population (or equivalent), specific scale 
experience (or equivalent), and certification required (if applicable) will be listed and used to 
determine whether a rater is approved for a given assessment. Proposed raters who do not 
meet specific criteria but who may be qualified based on unique circumstances may be 
individually reviewed by the sponsor study clinical team to determine whether or not a 
waiver may be issued. The rater must become certified to perform selected study assessments 
before he or she can participate in the conduct of the study. For specifically defined 
assessments, rater training and standardization exercises may be conducted, and written and 
signed documentation will be provided by the site for each rater’s certification. In return, 
each site will be provided written and signed documentation outlining each rater’s 
certification for specific study assessments. Recertification may be required at periodic 
intervals during the study. The raters who administer specific study assessments will be 
documented in a centralized location and all site staff who administer ratings will be verified 
in the site study documentation during the conduct of the study. 


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8.3. Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.3. 
AE will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1 and Section 10.7). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner. 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days, except as indicated below, after the last administration of the 
study intervention. 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including Visit 
19. 
Follow up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment. 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 


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Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the CT SAE Report Form. 
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Section 10.3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF 
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
The investigator is to record on the CRF all directly observed, and all spontaneously reported 
AEs and SAEs reported by the participant. 
8.3.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3. Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Section 10.3. 


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8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics 
Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/IEC, if appropriate according to local requirements. 
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure 
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness. 
8.3.5.1. Exposure During Pregnancy 
An EDP occurs if: 
• A female participant is found to be pregnant while receiving or after discontinuing 
study intervention. 
• A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception. 
• A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy: 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact. 
• A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then exposes his female 
partner prior to or around the time of conception. 


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The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
• If EDP occurs in a participant or a participant’s partner, 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. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after 
the last dose. 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file. 
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). 
Abnormal pregnancy outcomes are considered SAEs. 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, including 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 study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 


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the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.3.5.2. Exposure During Breastfeeding 
An exposure during breastfeeding occurs if: 
• A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention. 
• A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact. 
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so 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. 
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, the 
SAE is reported together with the exposure during breastfeeding. 
8.3.5.3. Occupational Exposure 
An occupational exposure occurs when, a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE. Such persons may 
include healthcare providers, family members, and other roles that are involved in the trial 
participant’s care. 
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE. The information 
must be reported using the CT SAE Report Form. Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file. 
8.3.6. Cardiovascular and Death Events 
Deaths and AEs related to cardiovascular events will be adjudicated (Section 9.6) 


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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.3.8. Adverse Events of Special Interest 
Refer to Section 8.2.9 for definitions of adverse events of special interest (AESIs). 
All AESIs must be reported as an AE or SAE following the procedures described in 
Section 8.3.1 through Section 8.3.4. An AESI is to be recorded as an AE or SAE on the CRF. 
In addition, an AESI that is also an SAE must be reported using the CT SAE Report Form. 
8.3.8.1. Lack of Efficacy 
Lack of efficacy is reportable to Pfizer Safety only if associated with an SAE. 
8.3.9. Medical Device Deficiencies 
Not applicable. 
8.3.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. 
Exposures to the study intervention 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 
 
Medication errors include: 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participant. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
In the event of a medication dosing error, the sponsor should be notified within 24 hours. 


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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. 
8.4. Treatment of Overdose 
For this study, any dose of PF-06651600 greater than 800 mg within a 24-hour time period 
will be considered an overdose. 
There is no specific antidote or specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should: 
1. Contact the Medical Monitor within 24 hours. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-06651600 (whichever 
is longer). 
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 
4. Overdose is reportable to Safety only when associated with a SAE. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7. Genetics 
8.7.1. Specified Genetics 
Genetics (specified analyses) are not evaluated in this study. 
8.7.2. Banked Biospecimens for Genetics 
Banked biospecimens for genetics are not included in this study. 
8.8. Biomarkers 
Biomarkers are not evaluated in this study. 
8.8.1. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study. 


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8.8.2. Specified Protein Research 
Specified protein research is not included in this study. 
8.8.3. Specified Metabolomic Research 
Specified metabolomic research is not included in this study. 
8.8.4. Banked Biospecimens for Biomarkers 
Banked biospecimens for biomarkers are not included in this study. 
8.9. Immunogenicity Assessments 
Immunogenicity assessments are not applicable in this study. 
8.10. Health Economics 
Not applicable: Health economic/medical resource utilization parameters are not evaluated in 
this study. 
. 


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9. STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment. 
9.1. Estimands and Statistical Hypotheses 
For the primary safety endpoint, there is no formal hypothesis testing. The analyses will 
focus on estimation. Summary statistics for each group with 95% confidence intervals will be 
provided. 
Estimands 
Not applicable since there is no formal statistical hypothesis testing for this study. 
9.2. Sample Size Determination 
Approximately 60 adults 18 to 50 years of age will be randomized in a 1:1 allocation ratio to 
either the PF-06651600 200 mg QD/50 mg QD dose group or the placebo group. 
For the primary safety endpoint, change from baseline in I-V interwave latency on BAEP at 
Month 9, the published standard deviations for I-V interwave latency on BAEP range from 
0.1 to 0.3 ms. Assuming the standard deviation of 0.2 ms, and assuming standard deviation of 
change from baseline is similar as the standard deviation of actual score, the half-width of 
95% confidence interval for the group will be 0.07 ms for 30 participants per group. 
9.3. Analysis Sets 
For purposes of analysis, the following populations are defined: 
 
Population 
Description 
Efficacy 
All randomized participants taking at least 1 dose of study intervention. 
Data will be summarized according to the intervention they were 
assigned. 
Safety 
All participants taking at least 1 dose of study intervention. Participants 
will be analyzed according to the intervention they actually received. 
 
9.4. Statistical Analyses 
The statistical analysis plan will be developed and finalized before database lock and will 
describe the participant populations to be included in the analyses, and procedures for 
accounting for missing, unused, and spurious data. This section is a summary of the planned 
statistical analyses of the primary, the secondary, and the exploratory endpoints. 


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9.4.1. Timing of the Analyses 
There will be 3 Clinical Study Reports (CSRs) for this study: one PCD-CSR, and two 
supplemental CSRs. 
 
The PCD-CSR will include the primary analysis for this study, which will be conducted 
following the PCD at Month 9 (TP1) (Section 4.4), and after the Month 9 data are cleaned 
and locked for all participants. The following data will be included: 
• Efficacy data through Month 9 (TP1) 
• All safety data collected through the PCD data cut-off date 
 
The supplemental CSR 1 will be prepared after the last participant completes the 4-week 
follow-up visit, or the Month 15E visit (TP2) if the last participant is enrolling in TP3. This 
CSR will include: 
• Efficacy through Month 15E (TP1+TP2) 
• All safety data collected through the cut-off date for this CSR. 
 
The supplemental CSR 2 will be focused on safety and efficacy data from TP3 and will be 
prepared after the last participant completes the last visit or discontinues from the study. 
 
 
9.4.2. Efficacy Analyses 
Efficacy data will be summarized by the treatment assignment based on efficacy population. 
The baseline is defined as the last measurement before the first dose in the placebo-controlled 
phase. 
The secondary endpoints for SALT include both the overall SALT and AA SALT scores. 
The overall SALT score includes hair loss regardless of etiology (ie, scalp hair loss due to 
both non-AA and AA). The non-AA SALT score only takes into account scalp hair loss other 
than that due to AA and is required to be assessed only at: 
• Month 9 (end of TP1) (or Month 6 for those participants, who enter the active therapy 
extension phase at Month 6), 
• Month 15E (end of TP2) or Early Termination visit (as appropriate), and 
• Month 51E (end of TP3) or Early Termination visit (as appropriate). 
The AA SALT score at each visit will be calculated using non-AA SALT scores as follows: 
• the non-AA SALT score collected at Month 9 (or Month 6) or the Early Termination 
visit (as appropriate) will be used for visits in TP1. 


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• the non-AA SALT score collected at Month 15E or the Early Termination visit (as 
appropriate) will be used for visits in TP2, and 
• the non-AA SALT score collected at Month 51E or the Early Termination visit (as 
appropriate) will be used for visits in TP3. 
• The formula for deriving the AA SALT score is given by: AA SALT score = overall 
SALT score – non-AA SALT score. 
 
PCD CSR (Month 9; TP1) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
For PGI-C response, for the placebo-controlled phase, number and 
percentage with 95% confidence interval (based on Clopper-Pearson 
method) by treatment group, and treatment difference with 95% confidence 
interval (based on Chan and Zhang’s exact method(56)) will be presented. 
Participants who discontinue from the study for any reason or who switch 
to active therapy extension phase before Month 9 will be considered as non- 
responders. 
• 
In the placebo-controlled phase, change from baseline in overall and AA 
SALT score will be analyzed using linear mixed-effects model with 
baseline, treatment group, visit and treatment group by visit interaction as 
fixed effects, and participant as a random effect with unstructured 
covariance matrix assumption. The estimated mean, mean difference, with 
95% confidence interval based on the model will be presented at each time 
point. 
Exploratory 
• There are no exploratory efficacy endpoints included in this CSR 
 
 
Supplementary CSR 1 (Month 15E; TP2) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
For PGI-C response in the active therapy extension phase, number, and 
percentage with 95% confidence interval (based on Clopper–Pearson 
method) by initial treatment group will be presented based on observed 
data. 
• 
For overall and AA SALT score in the active therapy extension phase, 
descriptive statistics will be presented by initial treatment group. Observed 
data will be used. 
Exploratory 
• 
There are no exploratory efficacy endpoints included in this CSR. 
 
 
Supplementary CSR 2 (Month 51E; TP3) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
There are no secondary efficacy endpoints included in this CSR. 


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Supplementary CSR 2 (Month 51E; TP3) 
Endpoint 
Statistical Analysis Methods 
Exploratory 
• 
For PGI-C response in TP3, number, and percentage with 95% confidence 
interval (based on Clopper–Pearson method) by initial treatment group will 
be presented based on observed data. 
• 
For overall and AA SALT score in TP3, descriptive statistics will be 
presented by initial treatment group. Observed data will be used. 
 
9.4.3. Safety Analyses 
The safety analyses will be summarized by initial treatment group in the safety population 
based on observed data. The baseline is defined as the last measurement before the first dose 
in the placebo-controlled phase. 
All standard safety summary such as the incidence of safety events will be summarized by 
the initial treatment group for the placebo-control phase, the active therapy extension phase 
and TP3 extension phase. For initial active group, the overall summary for the whole study 
duration will also be provided. 
 
PCD CSR (Month 9; TP1) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
The primary endpoint is change from baseline in I-V 
interwave latency on BAEP at Month 9. It will be 
analyzed using linear mixed-effects model with baseline, 
treatment group, visit (Months 6 and 9) and treatment 
group by visit interaction as fixed effects, and subject as a 
random effect with unstructured covariance matrix 
assumption. For participants who switch to the active 
therapy extension phase at Month 6, only their data 
through Month 6 will be included in the analysis of the 
placebo-controlled period. The estimated means, with 
their standard errors and 95% confidence intervals based 
on the model will be presented. 
Secondary 
• 
Change from baseline in I-V interwave latency on BAEP 
during the placebo-controlled phase will be analyzed 
using linear mixed-effects model with baseline, treatment 
group, visit (Months 6 and 9) and treatment group by 
visit interaction as fixed effects, and participant as a 
random effect with unstructured covariance matrix 
assumption. The estimated means, with their standard 
errors and 95% confidence intervals based on the model 
will be presented. For data in the active therapy extension 
phase, descriptive statistics will be presented. 
• 
For change from baseline in IENFD at Month 9 and 
Month 15E and change from baseline in axonal 
dystrophy in skin punch biopsies at Month 9 and Month 
15E: descriptive statistics will be presented. 
• 
Change and percent change from baseline in amplitude of 
wave V: the same method linear mixed-effect model as 


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PCD CSR (Month 9; TP1) 
Endpoint 
Statistical Analysis Methods 
the I-V interwave latency will be used for Month 6 and 
Month 9 data. For data in the active therapy extension 
phase, descriptive statistics will be presented. 
• 
Absence of wave V on BAEP will be summarized 
descriptively using number and percentage of participants 
by treatment group at each intensity level. 
• 
The incidence rates of safety events, significant clinical 
abnormalities, vital signs and ECG will be summarized 
descriptively using number and percentage. 
 
Supplementary CSR 1 (Month 15E; TP2) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary safety endpoints included in the 
supplemental CSR 1. 
Secondary 
• 
For change from baseline in I-V interwave latency on 
BAEP: descriptive statistics will be presented. 
• 
For change from baseline in IENFD at Month 9 and 
Month 15E and change from baseline in axonal 
dystrophy in skin punch biopsies at Month 9 and Month 
15E: descriptive statistics will be presented. 
• 
Change and percent change from baseline in amplitude of 
wave V: descriptive statistics will be presented. 
• 
Absence of wave V on BAEP will be summarized 
descriptively using number and percentage of participants 
by treatment group at each intensity level. 
• 
The incidence rates of safety events, significant clinical 
abnormalities, vital signs and ECG will be summarized 
descriptively using number and percentage. 
 
Supplementary CSR 2 (Month 51E; TP3) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary safety endpoints included in the 
supplemental CSR 2. 
Secondary 
• 
The incidence rates of safety events, significant clinical 
abnormalities and vital signs in TP3 will be summarized 
descriptively using number and percentage. 
 
9.5. Interim Analyses 
There is no formal interim analysis planned in this study. However, if required, interim 
analyses may be performed for study monitoring for internal decision making, due to 
regulatory requests, or to support regulatory submissions. As no statistical hypotheses will be 
tested in this study, there are no issues of protecting the Type I error rate. 


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9.6. Data Monitoring Committee or Other Independent Oversight Committee 
This study will use a data monitoring committee (DMC). The DMC is independent of the 
study team and includes only external members. The DMC charter describes the role of the 
DMC in more detail. 
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by DMC to alter the conduct of 
the study will be forwarded to the appropriate Pfizer personnel for final decision. Pfizer will 
forward such decisions, which may include summaries of aggregate analyses of safety data, 
to regulatory authorities, as appropriate. 
Independent safety adjudication committees will be used for opportunistic infections, 
cardiovascular events, neurological /audiological events, and malignancy events. 


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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
 
10.1.1. Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the 
following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o Applicable ICH Good Clinical Practice (GCP) Guidelines 
o Applicable laws and regulations, including applicable privacy laws 
• 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted 
to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC 
before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary 
to eliminate an immediate hazard to study participants. 
• 
The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
• 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an 
applicable regulatory authority in any area of the world, or if the investigator is 
aware of any new information that might influence the evaluation of the benefits 
and risks of the study intervention, 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 participants against any 
immediate hazard, and of any serious breaches of this protocol or of ICH GCP that 
the investigator becomes aware of. 


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10.1.2. Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study. The participant should be 
given sufficient time and opportunity to ask questions and to decide whether or not 
to participate in the trial. 
• 
Participants must be informed that their participation is voluntary. Participants will 
be required to sign a statement of informed consent that meets the requirements of 
21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or 
study center. 
• 
The investigator must ensure that each study participant is fully informed about the 
nature and objectives of the study, the sharing of data related to the study and 
possible risks associated with participation, including the risks associated with the 
processing of the participant’s personal data. 
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant. 
• 
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 
The investigator further must ensure that each study participant is fully informed 
about his or her right to access and correct his or her personal data and to withdraw 
consent for the processing of his or her personal data. 
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICD. 
• 
Participants must be re-consented to the most current version of the ICD(s) during 
their participation in the study. 
• 
A copy of the ICD(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICD. 


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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of remaining mandatory samples for optional exploratory 
research. The investigator or authorized designee will explain to each participant the 
objectives of the exploratory research. Participants will be told that they are free to refuse to 
participate and may withdraw their consent at any time and for any reason during the storage 
period. A separate signature will be required to document a participant's agreement to allow 
any remaining specimens to be used for exploratory research. Participants who decline to 
participate in this optional research will not provide this separate signature. 
10.1.4. Data Protection 
• 
All parties will comply with all applicable laws, including laws regarding the 
implementation of organizational and technical measures to ensure protection of 
participant data. 
• 
Participants’ personal data will be stored at the study site in encrypted electronic 
and/or paper form and will be password protected or secured in a locked room to 
ensure that only authorized study staff have access. The study site will implement 
appropriate technical and organizational measures to ensure that the personal data 
can be recovered in the event of disaster. In the event of a potential personal data 
breach, the study site shall be responsible for determining whether a personal data 
breach has in fact occurred and, if so, providing breach notifications as required by 
law. 
• 
To protect the rights and freedoms of natural persons with regard to the processing 
of personal data, participants will be assigned a single, participant-specific 
numerical code. Any participant records or datasets that are transferred to the 
sponsor will contain the numerical code; participant names will not be transferred. 
All other identifiable data transferred to the sponsor will be identified by this single, 
participant-specific code. The study site will maintain a confidential list of 
participants who participated in the study, linking each participant’s numerical code 
to his or her actual identity. In case of data transfer, the sponsor will protect the 
confidentiality of participants’ personal data consistent with the Clinical Study 
Agreement and applicable privacy laws. 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
See Section 9.6. 
10.1.5.2. Adjudication/Review Committee Submission 
There will be 4 adjudication committees: one for opportunistic infections, one for 
cardiovascular events, one for neurological/audiological safety, and one for malignancy. The 
identification of events requiring submission to an adjudication/review committee will be 
made by the study site and communicated to Pfizer or designee. In addition, events requiring 


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review, including opportunistic infections, cardiovascular, neurological/audiological or 
malignancy events may also be identified by the Pfizer Study Team or designee during the 
review of participant data listings or by site monitors during routine monitoring of 
participant’s study records. The Pfizer Study Team or designee will notify the study site of 
any events should they identify. 
The Pfizer Study Team or designee will provide a listing of specific documents needed to 
support event adjudication by the Adjudication/Review Committees. Obtaining and 
submitting the documentation will be the responsibility of the study site. Event 
documentation will vary with the event requiring adjudication and may include (but not be 
limited to): hospital discharge summaries, operative reports, clinic notes, ECGs, diagnostic 
tests, pathology reports, autopsy reports, imaging reports (eg, MRI) and death certificate 
information, as applicable. 
10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs). 
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 results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in participants) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law. 
EudraCT 
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements. 
www.pfizer.com 
Pfizer posts public disclosure synopses (Clinical Study Report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the 
corresponding study results are posted to www.clinicaltrials.gov. 


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Documents within marketing authorization packages/submissions 
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website. Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods. Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data. 
Policy 0070 applies to new marketing authorization applications submitted via the 
centralized procedure since 01 January 2015 and applications for line extensions and for new 
indications submitted via the centralized procedure since 01 July 2015. 
Data Sharing 
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted. 
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
10.1.7. Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (eg, laboratory 
data). The investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the CRF. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• 
The investigator must ensure that the CRFs are securely stored at the study site in 
encrypted electronic and/or paper form and are password protected or secured in a 
locked room to prevent access by unauthorized third parties. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
This verification may also occur after study completion. It is important that the 
investigator(s) and their relevant personnel are available during the monitoring visits 
and possible audits or inspections and that sufficient time is devoted to the process. 
• 
Monitoring details describing strategy (eg, risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk- 
Based Monitoring), methods, responsibilities and requirements, including handling 


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of noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan and contracts. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
• 
Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• 
Records and documents, including signed ICDs, pertaining to the conduct of this 
study must be retained by the investigator for 15 years after study completion unless 
local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of 
the sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. The investigator must ensure that the records 
continue to be stored securely for so long as they are maintained. 
• 
When participant data are to be deleted, the investigator will ensure that all copies 
of such data are promptly and irrevocably deleted from all systems. 
• 
The investigator(s) will notify sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will 
cooperate with sponsor or its agents to prepare the investigator site for the 
inspection and will allow sponsor or its agent, whenever feasible, to be present 
during the inspection. The investigator site and investigator will promptly resolve 
any discrepancies that are identified between the study data and the participant's 
medical records. The investigator will promptly provide copies of the inspection 
findings to sponsor or its agent. Before response submission to the regulatory 
authorities, the investigator will provide sponsor or its agents with an opportunity to 
review and comment on responses to any such findings. 
10.1.8. Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must 
be explained. The investigator may need to request previous medical records or 
transfer records, depending on the study. Also, current medical records must be 
available. 


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• 
Definition of what constitutes source data can be found in the Clinical Monitoring 
Plan. 
• 
Description of the use of computerized system is documented in the Study 
Monitoring Plan. 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time upon notification to CRO if 
requested to do so by the responsible IRB/IEC or if such termination is required to protect the 
health of Study Participants. 
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol the contract will control as to termination rights. 
10.1.10. Publication Policy 
• 
The results of this study may be published or presented at scientific meetings by the 
Investigator after publication of the overall study results or one year after end of the 
study (or study termination), whichever comes first. 
• 
The investigator agrees to refer to the primary publication in any subsequent 
publications such as secondary manuscripts and submit all manuscripts or abstracts 


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to the sponsor 30 days before submission. This allows the sponsor to protect 
proprietary information and to provide comments and the Investigator will, on 
request, remove any previously undisclosed confidential information before 
disclosure, except for any study- or Pfizer intervention-related information 
necessary to the appropriate scientific presentation or understanding of the study 
results. 
• 
For all publications relating to the study, the Investigator will comply with 
recognized ethical standards concerning publications and authorship, including 
those established by the International Committee of Medical Journal Editors. 
• 
The sponsor will comply with the requirements for publication of the overall study 
results covering all Investigator sites. In accordance with standard editorial and 
ethical practice, the sponsor will support publication of multicenter studies only in 
their entirety and not as individual site data. In this case, a coordinating investigator 
will be designated by mutual agreement. 
• 
Authorship of publications for the overall study results will be determined by 
mutual agreement and in line with International Committee of Medical Journal 
Editors authorship requirements. 
• 
If publication is addressed in the clinical study agreement, the publication policy set 
out in this section will not apply. 
10.1.11. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card. The contact card 
contains, at a minimum, protocol and study intervention identifiers, participant 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 
participant’s participation in the study. The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study. For sites other than 
a Pfizer Clinical Research Unit (CRU), the contact number is not intended for use by the 
participant directly, and if a participant calls that number, he or she will be directed back to 
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10.2. Appendix 2: Clinical Laboratory Tests 
• The following safety laboratory tests will be performed at times defined in the SoA 
(Section 1.3) section of this protocol. Additional laboratory results may be reported 
on these samples as a result of the method of analysis or the type of analyzer used 
by the clinical laboratory, or as derived from calculated values. These additional 
tests would not require additional collection of blood. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess 
any perceived safety issues or as per local regulations. 
• 
The tests detailed in Table 2 will be performed by the central laboratory. (See 
laboratory manual.) 
• 
Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory 
results are used to make either a study intervention decision or response evaluation, 
the results must be entered into the CRF. 
• 
Pregnancy Testing 
o Refer to Section 5.1 Inclusion Criteria and Section 8.2.13 Pregnancy Testing for 
screening pregnancy criteria. For details of timing of recommended pregnancy 
testing see the SoA (Section 1.3). 
 
Table 2. 
Protocol Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
%Reticulocytes 
MCV 
MCH 
Platelet count 
WBC count 
Neutrophils 
Eosinophils 
Monocytes 
Basophils 
Lymphocytes 1 
BUN and creatinine 
Glucose 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (bicarbonate) 
AST, ALT 
Total bilirubin 
Direct and Indirect bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
Creatine Kinase2 
Follow-up testing for 
potential DILI cases3 
pH 
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte esterase 
Urobilinogen 
Urine bilirubin 
Microscopy4 
Urine culture5 
At screening only: 
• FSH6 
• Pregnancy test 
(β-hCG)7 
• Hepatitis C antibody 
• HIV8 
• HbA1C 
• HbsAg 
• HbcAb 
• HbsAb9 
• HBVDNA10 
• HCVAb 
• HCVRNA11 
• QFT-G test or T-Spot 
test12 
• Viral Screen13 
• Skin biopsies/swabs14 
• Fasting Lipid profile15 


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Table 2. 
Protocol Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
NOTES: 
1. Participants with absolute lymphocyte counts <500/mm3 (0.5 × 109/L) will be reflex tested for FACS 
TBNK until the absolute lymphocyte count resolves or stabilizes at a level acceptable to the 
investigator and the sponsor. 
2. In addition to re-testing creatine kinase 3× ULN, urine myoglobin will be performed as reflex testing 
for any participant with a creatine kinase >10 × ULN. For participants who have completed the Month 
15E Visit, creatine kinase and urine myoglobin will not be tested. 
3. In cases of suspected potential drug-induced-liver-injury (DILI), follow-up testing should be 
performed according to requirements in Section 10.5. 
4. Only if urine dipstick is positive for blood, nitrites, leukocyte esterase, and/or protein. 
5. Urine culture will be performed if urinalysis is positive for nitrite and/or leukocyte esterase or if 
clinically indicated. For participants who have completed the Month 15E, urine samples and urinalysis 
will be performed only if considered clinically indicated by the investigator. 
6. For confirmation of postmenopausal status only in females who are not using hormonal contraception 
or hormonal replacement therapy (HRT). 
7. Pregnancy tests (urine) for women of childbearing potential. In the event that urine pregnancy tests are 
not permitted at an institution, serum pregnancy tests must be utilized. Local urine testing will be standard 
for the protocol unless serum testing is required by local regulation or IRB/EC. 
8. HIV testing per local regulations. Participants who are positive for HIV antibodies will be screen 
failed. 
9. HBsAb will be performed as reflex testing for any participant who is HBsAg negative but HBcAb 
positive Please refer to Section 10.6 for testing algorithm, reflex testing, and full eligibility criteria. 
10. Additional reflex testing for hepatitis B virus deoxyribonucleic acid testing (HBVDNA) is also 
required for participants who are HBsAg negative and HBcAb positive in countries in which hepatitis 
B prevalence has been reported at a rate of >5.0% or if required by local standard of care. Please refer 
to Section 8.2.10.3 and Section 10.6 for testing algorithm, reflex testing, and full eligibility criteria. 
11. HCVRNA will be performed as reflex testing for any participant who is HCVAb positive. 
12. The QFT G test is preferred; however, the T Spot test is also permitted as described in 
Section 8.2.10.1. A PPD test can be substituted for the QFT G test or T Spot test only under specific 
circumstances described in Exclusion criterion 21 in Section 5.2 and Section 8.2.10.1. 
13. A serum sample will be collected at Day 1 and submitted to the central lab. The sample will be stored 
and analyzed at a later date only at the sponsor’s request. In certain cases of suspected viral infection 
(eg, disseminated herpes zoster or varicella), the sponsor may request to analyze the sample to 
determine if the participant had exposure to that virus. 
14. When required in cases of skin rash adverse events. See applicable sections for herpetiform rash 
(Section 8.2.9.2.1) and potential drug related rash (Section 8.2.9.2.2). 
15. Lipid profile panel will include total cholesterol, low density lipoprotein (LDL), high density 
lipoprotein (HDL), and triglycerides. A minimum of 8-hour fasting is required for lipid profile 
evaluation. Lipid profile panel will not be tested after the Month 15E Visit. 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unblind the study will not be reported to investigative 
sites or other blinded personnel until the study has been unblinded. 


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1. Definition of AE 
 
AE Definition 
• An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Any abnormal 
laboratory test results that meet any of the conditions below must be recorded as an 
AE: 
• Is associated with accompanying symptoms. 
• Requires additional diagnostic testing or medical/surgical intervention. 
• 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. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self- 
harming intent. Such overdoses should be reported regardless of sequelae. 


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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.3.2. Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease). 
 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. 
Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 


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influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
• 
Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious. The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product. The terms “suspected transmission” and “transmission” are 
considered synonymous. These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel. Such cases are also 
considered for reporting as product defects, if appropriate. 
10.3.3. Recording and Follow-Up of AE and/or SAE 
 
AE and SAE Recording/Reporting 
The table below summarizes the requirements for recording adverse events on the CRF 
and for reporting serious adverse events on the Clinical Trial (CT) Serious Adverse Event 
(SAE) Report Form to Pfizer Safety. These requirements are delineated for 3 types of 
events: (1) SAEs; (2) non-serious adverse events (AEs); and (3) exposure to the study 
intervention under study during pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information 


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Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure 
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding. 
Occupational exposure is 
not recorded. 
All (And EDP 
supplemental form for 
EDP) 
Note: Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• The investigator will then record all relevant AE/SAE information in the CRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the AE/SAE CRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort, and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 


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• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with a SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
• If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor" and "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. 
 
Follow-up of AEs and SAEs 


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• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• If a participant dies during participation in the study or during a recognized follow- 
up period, the investigator will provide Pfizer Safety with a copy of any 
post-mortem findings including histopathology. 
• New or updated information will be recorded in the originally completed CRF. 
• The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information. 
10.3.4. Reporting of SAEs 
 
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone. 
 
SAE Reporting to Pfizer Safety via Paper CRF 
• Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to Pfizer Safety. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 


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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in athletes) and a menstrual cycle cannot be confirmed 
before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry. 
Note: Documentation for any of the above conditions can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using 
hormonal contraception or hormonal replacement therapy (HRT). This test 
is not to be performed for WOCBP (refer to Schedule of Activities Section 
1.3) 
• 
Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT at least 14 days prior to FSH testing to allow confirmation of 
postmenopausal status before study enrollment. 
• 
To confirm post-menopausal status, females taking hormonal contraception or 
HRT must discontinue these for at least 2 weeks prior to performing FSH testing 


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and must remain abstinent during this period until post-menopausal status is 
confirmed. 
Contraception Guidance: 
No contraception methods are required for male participants in the study. 
The following applies to female participants who are considered WOCBP. 
Permitted Highly Effective Contraceptive Methods 
1. Oral, injectable, or implantable progestogen-only hormone contraception associated 
with inhibition of ovulation. 
2. Intrauterine device (IUD). 
3. Intrauterine hormone-releasing system (IUS). 
4. Bilateral tubal occlusion or bilateral tubal ligation. 
5. Oral, intravaginal, transdermal, or injectable combined (estrogen- and progestogen- 
containing) hormonal contraception associated with inhibition of ovulation used in 
combination with a barrier method. 
1. Acceptable barrier methods include: 
• Male or female condom with or without spermicide; 
• Cervical cap, diaphragm, or sponge with spermicide. 
Male condom and female condoms should not be used together (due to risk of failure 
with friction). 
6. Vasectomized partner. 
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP, and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be 
used. The spermatogenesis cycle is approximately 90 days. 
7. Sexual abstinence. 
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 


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Additionally, contraceptive use should be consistent with local regulations regarding the use 
of contraceptive methods for those participating in clinical trials. 


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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI). Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (×ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.” 
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2× ULN) by several days 
or weeks. The increase in TBili typically occurs while AST/ALT is/are still elevated above 
3× ULN (ie, AST/ALT and TBili values will be elevated within the same 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 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values: 
• Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3× ULN AND a TBili value 
>2× ULN with no evidence of hemolysis and an alkaline phosphatase value <2× ULN 
or not available; 
• For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline: 
o 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). 
o Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1× ULN or if the value reaches >3× ULN 
(whichever is smaller). 


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s Law, additional laboratory tests should include albumin, creatine kinase (CK), direct 
and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time 
(PT)/international normalized ratio (INR), total bile acids, and alkaline phosphatase. 
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology. A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected. Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) and collection of serum sample for acetaminophen drug and/or protein 
adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 


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10.6. Appendix 6: Hepatitis B Testing Alogrithm and Full Eligibility Criteria 
For participants in countries in which hepatitis B prevalence has been reported at a 
rate of >5.0%a or if required by local standard of care, participants will be tested as 
follows: 
1. At screening, HsBsAg and HBcAB will be tested: 
a. If both tests are negative, the participant is eligible for study inclusion. 
b. If HBsAg is positive, the participant must be excluded from participation in the study. 
c. If HBsAg is negative and HBcAb is positive, HBsAb and HBVDNA reflex testing is 
required: 
i. If HBsAb is negative, the participant must be excluded from participation in the 
study; 
ii. If HBVDNA is detected, the participant must be excluded from participation in 
the study; 
iii. If HBsAb is positive and HBVDNA is undetectable, the participant is eligible for 
study inclusion. If the subject is included in the study, for subsequent visits 
HBVDNA testing must be performed according to the SoA (Section 1.3). 
For participants in all other countries, participants will be tested as follows: 
2. At screening, HBsAg and HBcAb will be tested: 
a. If both tests are negative, the participant is eligible for study inclusion. 
b. If HBsAg is positive, the participant must be excluded from participation in the study. 
c. If HBsAg is negative and HBcAb is positive, HBsAb reflex testing is required: 
i. If HBsAb is negative, the participant must be excluded from participation in the 
study; 
ii. If HBsAb is positive, the participant is eligible for study inclusion. If the 
participant is included in the study, for subsequent visits no hepatitis B testing is 
required. 
 
 
 
 
 
a Razavi-Shearer D, Gamkrelidze I, Nguyen MH, et al. Global prevalence, treatment, and prevention of 
hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol 2018; 3(6);383-403. 


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10.7. Appendix 7: Guidelines for Participant Safety Monitoring and Discontinuations 
These guidelines for participant safety monitoring and discontinuation are to be applied to all 
participants in Study B7981037. Additional individual participant 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 
participant may be withdrawn at any time at the discretion of the investigator. 
For the purposes of safety monitoring and discontinuation, baseline values will be defined as 
follows: 
• 
Baseline values will be defined as the most recent pre-dose values before dosing on 
Day 1 for all participants. 
10.7.1. Monitoring 
All potential treatment-related events of rash will be followed up until resolution or 
agreement with Pfizer. 
The following laboratory abnormalities require re-testing until resolution or agreement 
with Pfizer: 
 
Table 3. 
Laboratory Retesting Criteria 
 
Laboratory Variable 
Laboratory Value 
Re-testing Timeframea 
Hematology 
Absolute Neutrophil Count 
<1000/mm3 (<1.0 × 109/L) 
Within 1 week 
Hemoglobin 
<10.0 g/dL (<6.21 mmol/L or <100 g/L) 
Within 1 week 
Platelet count 
<100,000/mm3 (<100 × 109/L) 
Within 1 week 
Absolute Lymphocyte Countb 
<600/mm3 (<0.6 × 109/L) 
Within 1 week 
Serum Chemistry 
Creatine kinasec 
>3 × ULN 
Within 1 week 
Aspartate aminotransferase 
See Section 10.5 for potential cases of 
drug‑induced liver injury. 
Within 48 hours 
Alanine aminotransferase 
See Section 10.5 for potential cases of 
drug‑induced liver injury. 
Within 48 hours 
Total bilirubin 
See Section 10.5 for potential cases of 
drug‑induced liver injury. 
Within 48 hours 
a. 
Based on awareness of the abnormal result. 
b. Participants with absolute lymphocyte count <500/mm3 (0.5 × 109/L) will be reflex-tested for 
FACS-TBNK until the absolute lymphocyte count resolves or stabilizes at a level acceptable to the 
investigator and sponsor. 
c. 
In addition to re-testing creatine kinase >3× ULN, urine myoglobin will be performed as reflex testing 
for any participant with creatine kinase >10× ULN for visits on or before Month 15E. For participants who 
have completed the Month 15E Visit, creatine kinase and urine myoglobin will not be tested. 


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In case of positive urine pregnancy test, the participant will have study intervention 
interrupted and a serum sample collected on the same day (or as soon as possible) and 
submitted to the central laboratory for pregnancy testing. 
10.7.2. Discontinuation 
Treatment will be discontinued, and the participant withdrawn from this study 
following completion of the Early Termination visit and the Follow-up Visit (whenever 
possible) for: 
Adverse Events: 
• Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment or meeting other 
criteria that require the infection to be classified as serious adverse event; 
• Treatment-related SAEs; 
• Clinically meaningful, treatment-emergent declines in hearing or clinically 
meaningful, treatment-emergent changes in audiological assessments from baseline 
(refer to Audiometry Study Guide for details) are to be discussed with the sponsor for 
possible withdrawal from study; 
• Other serious or severe AEs, at the discretion of the investigator or sponsor. 
ECG Findings (up to Month 15E Visit): 
• Confirmed QTcF >500 ms; 
• Confirmed increase from baseline in QTcF of >60 ms. 
Study Intervention Interruptions: 
• Participants interrupting study intervention for more than 14 consecutive days are 
to be discussed with the sponsor for possible withdrawal from the study. 
Laboratory Abnormalities: 
All the following laboratory abnormalities require discontinuation if they are confirmed by 
re-test. Refer to the re-testing timeframes for laboratory abnormalities in Section 10.7.1: 
• Absolute Neutrophil Count <750/mm3 (<0.75 × 109/L). 
• Hemoglobin <9.0 g/dL (<5.59 mmol/L or <90 g/L) or a decrease of >30% from 
baseline (either criterion or both). 
• Platelet count <75,000/mm3 (<75.0 × 109/L). 


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• Absolute Lymphocyte Count <500/mm3 (<0.5 × 109/L). 
NOTE: Participants with absolute lymphocyte count <500/mm3 (0.5 × 109/L) will 
be reflex tested for FACS-TBNK until the absolute lymphocyte count resolves or 
stabilizes at a level acceptable to the investigator and sponsor. 
• Creatine kinase >10× ULN (for visits on or before Month 15E). 
NOTE: In addition to re-testing creatine kinase >3× ULN, urine myoglobin will 
be performed as reflex testing for any participant with creatine kinase >10 × ULN 
for visits on or before Month 15E. For participants who have completed the 
Month 15E visit, creatine kinase and urine myoglobin will not be tested. 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that meet 
ANY of the following: 
• >3× ULN with at least one total bilirubin value >2× ULN; 
• >3× ULN accompanied by signs or symptoms consistent with hepatic injury 
(eg, new onset elevated PT/INR); 
• Two sequential AST or ALT elevations >5× ULN, regardless of total bilirubin 
or accompanying signs or symptoms. 
NOTE: In each case, there is a need for additional investigations, such as review 
of ethanol, recreational drug, and dietary supplement consumption; testing for 
acute hepatitis A, B or C infection and biliary tract imaging should be promptly 
discussed with the sponsor or designee. 
Pregnancy: 
Female participants confirmed as pregnant during the study (see Section 8.3.5). 
Prohibited Medications: 
• Participants who are treated with any prohibited medication during the course of the 
study may require discontinuation. Participants who are administered a prohibited 
medication should be discussed with the sponsor for possible withdrawal from the 
study. 
Suicidal Ideation: 
• Participants with suicidal ideation associated with actual intent and a method or plan 
in the past year: a “yes” answer on items 4, 5, or on any question in the suicidal 
behavior section of the C-SSRS must be discontinued. The participant must be 


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referred to a mental health professional for appropriate evaluation and treatment or 
immediately referred to the Emergency Room at the investigator’s judgement. 
Discontinuation/End of Treatment Monitoring: 
• Any participant meeting discontinuation criteria must enter into the Follow-up Period 
with their first follow-up visit occurring 1 week after their last dose whenever 
possible, until the event has returned to normal or baseline levels or is deemed 
clinically stable. The procedures scheduled for Early Termination Visit will be 
performed on the last day the participant takes the study intervention or as soon as 
possible thereafter. The only exception to this is when a participant specifically 
withdraws consent for any further contact with him or her or persons previously 
authorized by the participant to provide this information. Additional follow-up visits 
may occur as needed until any clinically relevant abnormalities or adverse events 
have resolved, returned to a baseline state, or are deemed clinically stable. 
• Any participant that is discontinued from study intervention due to an auditory 
adverse event must have BAEP and auditory assessments performed at the time of 
discontinuation and repeated at 6 months after the last dose of study intervention. 
Refer to the Manual for BAEP Evaluations and the Audiology Study Guide for 
additional information. 
• Any participant that is discontinued from study intervention due to a neurological 
adverse event must have skin biopsy and neurological evaluations, including the 
Neuropathy Assessment, performed at the time of discontinuation, and repeated at 
6 months after the last dose of study intervention. Refer to the Manuals for General 
Neurological and Neuropathy Assessments for additional information. 


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10.8. Appendix 8: Prohibited and Permitted Concomitant CYP3A Inducers and 
Substrates 
Please note that this list addresses only CYP3A inducers and sensitive and moderate 
sensitive CYP3A substrates. Other prohibited medications for this trial are listed in 
Section 5.2. Refer to Section 6.5.1 for additional information regarding permitted 
medications for this trial, including CYP3A inhibitors. 
This is not an all-inclusive list. Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that are moderate to potent CYP3A 
inducers. If a medication is a sensitive or moderate sensitive CYP3A substrate and is not 
listed here, consultation with the Sponsor is required. 
10.8.1. Prohibited Concomitant CYP3A Inducers and Substrates 
 
Sensitive CYP3A Substratesa 
Moderate Sensitive CYP3A 
Substratesb 
Moderate to Potent CYP3A 
Inducersc 
Dasatinib 
Aprepitant 
Avasimibed 
Dronedarone 
Eliglustat 
Bosentan 
Ebastine 
Pimozide 
Barbiturates 
Lomitapide 
Rilpivirine 
Carbamazepined 
Nisoldipine 
Efavirenz 
Sirolimus 
Etravirine 
Tacrolimus 
Mitotaned 
Tolvaptan 
Modafinil 
Nafcillin 
Phenobarbitald 
Phenytoind 
Rifabutind 
Rifampin d 
St. John’s Wortd 
Talviraline 
a. 
Sensitive CYP3A substrates are drugs that demonstrate an increase in concentration-time curve (AUC) 
of ≥5-fold with strong index inhibitors of a given metabolic pathway in clinical drug-drug interaction (DDI) 
studies. 
b. Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold. In a 
situation where appropriate medical care of a participant requires the use of a prohibited CYP3A inducer: 
Moderate to potent inducers of CYP3A are not permitted in the study EXCEPT in emergency situations. 
Note: Mitotane is not permitted for any duration due to its long half-life; however, if necessary mitotane may 
be used in an emergency, however the participant will then be discontinued from the study. Topical 
(including skin or mucous membranes) application of antimicrobial and antifungal medications is permitted. 
c. 
All prohibited drugs that are CYP3A inducers require at least a 28 day or 5 half-lives (whichever is 
longer) washout prior to the first dose of study intervention. 
d. Notated as potent inducers. 


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10.8.2. Permitted Concomitant CYP3A Substrates 
 
Sensitive CYP3A Substratesa 
Moderate Sensitive CYP3A 
Substratesb 
Alfentanil 
Midazolam 
Alprazolam 
Avanafil 
Naloxegol 
Atorvastatin 
Buspirone 
Quetiapine 
Colchicine 
Darifenacin 
Sildenafil 
Rivaroxaban 
Eletriptan 
Simvastatin 
Tadalafil 
Eplerenone 
Ticagrelor 
Felodipine 
Triazolam 
Lovastatin 
Vardenafil 
Lurasidone 
a. 
Sensitive CYP3A substrates are drugs that demonstrate an increase in concentration-time curve (AUC) 
of ≥5-fold with strong index inhibitors of a given metabolic pathway in clinical drug-drug interaction (DDI) 
studies. 
b. Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold. 


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10.9. Appendix 9: Alternative Measures During Public Emergencies 
The alternative study measures described in this section are to be followed during public 
emergencies, including the coronavirus disease-2019 (COVID-19) pandemic. This appendix 
applies for the duration of the COVID-19 pandemic globally and will become effective for 
other public emergencies only upon written notification from Pfizer. NOTE: Any deviations 
from the SoA (Section 1.3) or the protocol (eg, missed or partially completed procedures or 
assessments) must be reported to the Sponsor in a timely manner and will be reported by the 
Sponsor as a protocol deviation. 
Procedures which are missed due to disruptions related to a public emergency, including the 
COVID-19 pandemic, are required to be performed at the next available opportunity, even if 
outside of a protocol-specified visit window. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
In this appendix, safety assessment terms include 1) special safety assessments (audiological 
evaluations, including BAEP, by the audiologist, neurological evaluation by the neurologist, 
and the skin biopsy) and 2) usual safety assessments (all other safety evaluations). 
10.9.1. Eligibility 
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing is not 
mandated for this study, local clinical practice standards for testing should be followed. A 
participant should be excluded if he/she has a positive test result for SARS-CoV2 infection, 
is known to have asymptomatic infection, or is suspected of having SARS-CoV2. 
Participants with active infections are excluded from study participation per Exclusion 
Criterion 19. When the infection resolves, the potential participant may be considered for re- 
screening. In addition, the following criteria apply: 
• The participant must be able to perform all Screening and Day 1 procedures per the 
SoA (Section 1.3) at the study site (CXR, skin biopsy, SALT) and/or designated 
ancillary facility (eg, audiological evaluations and neurological evaluations) to 
determine whether the participant meets eligibility criteria for the study. This includes 
collection and resulting of laboratory assessments through the central laboratory 
vendor. 
• The participant must meet eligibility criteria for the study and have had the initial 
Day 1 skin biopsy performed. 
• At the time of Randomization it must be confirmed that the participant will be able to 
have the Month 1 and Month 3 safety laboratory tests collected/performed at the 
study site or an alternative clinical laboratory facility (including the participant’s 
home, as available) according to the windows in Section 10.9.3. 
If a participant does not meet the criteria described above, they cannot be enrolled in the 
study. 


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10.9.2. Telehealth Visits 
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the SoA (Section 1.3) or 
unplanned visits. Telehealth visits may be used to continue to assess participant safety and 
collect data points. Telehealth includes the exchange of healthcare information and services 
via telecommunication technologies (eg, audio, video, video-conferencing software) 
remotely, allowing the participant and the investigator to communicate on aspects of clinical 
care, including medical advice, reminders, education, and safety monitoring. The following 
assessments must be performed during a telehealth visit: 
• Review dosing logs and record investigational product, including doses taken and any 
interruptions in intake of investigational product (ie, missed doses) since the last 
contact, and calculate compliance. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.3. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
• For WOCBP: Review and record contraceptive method and results 
of pregnancy testing. Confirm that the participant is adhering to the contraception 
method(s) required in the protocol. Refer to Appendix 4 and Section 10.9.3.1 of this 
appendix regarding pregnancy tests and to Section 5.3.1 of this protocol regarding 
contraception checks. 
• Body temperature and collection method (eg, oral, tympanic, axillary), pulse rate, and 
respiratory rate (measured by study participant/caregiver). 
• Collection of interim audiological history (using Part 1 in the Audiometry Guide 
Worksheet for Post Day 1 visits) at visits requiring audiological evaluation with entry 
of clinically significant changes onto the AE section of the eCRF, as appropriate. 
• Collection of interim neurological history (using General Neurology and Neuropathy 
Assessment Completion Guidelines) must be obtained, with entry of clinically 
significant changes onto the AE section of the eCRF, as appropriate. 
• Administration of the C-SSRS performed by a qualified rater. As per 
Section 8.2.11.1, if there are “yes” answers on items 4 or 5 of the suicidal ideation 
section or on any question in the suicidal behavior section of the C-SSRS, the 
participant will be discontinued from the study and referred to a mental health 
professional for appropriate evaluation and treatment. 
NOTE: If the investigator determines that additional evaluation is warranted based on the 
information collected during the remote visit described above, follow-up is required to be 
performed, with results submitted to and reviewed by the investigator prior to shipping 
investigational product to the participant. 
Study participants must be reminded to promptly notify site staff about any change in their 
health status. 


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The SALT and the PGI-C are not assessed if the visit is not onsite. 
10.9.3. Alternative Facilities for Safety Assessments 
10.9.3.1. Laboratory Testing (Usual Safety Assessments) 
With the exceptions noted in Section 10.9.1 for Screening and Day 1, if a study participant is 
unable to visit the site for protocol-specified safety laboratory evaluations, testing may 
be conducted at a local laboratory if permitted by local regulations. The local laboratory may 
be a standalone institution or within a hospital. Collection of blood and urine samples may 
also be performed at the participant’s home per Section 10.9.5. 
The following safety laboratory evaluations may be performed at a local laboratory or in the 
participant’s home: 
• Hematology; 
• Serum chemistry; 
• Lipid panel (for visits on or before Month 15E); 
• Urinalysis (for visits after Month 15E urinalysis will be performed only if considered 
clinically indicated by the investigator); 
• Pregnancy testing (for WOCBP); 
• Tuberculosis testing; 
• Refer to the SoA (Section 1.3) for visits at which these tests are required and to 
Section 10.2 for additional details regarding these tests. 
If it is not possible for the participant to have the above tests completed within the visit 
window specified in the SoA (Section 1.3), an extended window may be allowed to collect 
samples for these laboratory tests, provided that the investigator has performed the remote 
visit as described above, assessed each case, and determined that it would not increase risk to 
a participant. The extended windows for laboratory sample collection for each study visit are 
noted in Table 4. These windows apply only to laboratory samples collected during 
interruptions due to public emergencies, including the COVID-19 pandemic, based upon 
written notification from Pfizer. If the laboratory samples are not collected within the 
specified extended window for the visit, the participant must temporarily withhold 
investigational product until the required laboratory samples can be collected. 
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/ 
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible and must be received and reviewed by the investigator within 14 days 
after they are collected in order to determine eligibility to continue dosing. In addition, 
laboratory test results from the previous visit must be available and reviewed by the 
investigator prior to shipping investigational product at the current visit. The local laboratory 
reports should be filed in the participant’s source documents/medical records. Relevant data 
from the local laboratory report should be recorded on the CRF. 
Special attention should be paid to ensure that laboratory results are checked against the 
Guidelines for Participant Safety Monitoring and Discontinuations in Section 10.7 and that 
required follow-up is performed as applicable. 


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If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 IU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. Urine pregnancy test results may be collected based on information provided 
by the participant (or their legally authorized representative, if appropriate) during the remote 
visit. The urine pregnancy test result must be available prior to dispensing or shipping 
investigational product to a participant. The pregnancy test outcome should be 
documented in the participant’s source documents/medical records and relevant data 
recorded on the CRF. It should be confirmed that the participant is adhering to the 
contraception method(s) required in the protocol. 
 
Table 4. 
Windows for Remote Visits, Laboratory Sample Collections, and Special 
Safety Assessments if Required due to Public Emergencies Including 
COVID-19 
 
Visit 
Identifier 
Visit Month 
(Day in Study) 
Remote Visit 
Window 
(Day in Study)a 
Lab Collection 
Window 
(Day in Study)b 
Special Safety 
Assessment Window 
(Day in Study)c 
3 
Month 1 
(Day 31) 
±3 days 
(Day 28-34) 
-7/ +14 days 
(Day 24-45) 
NA 
4 
Month 3 
(Day 91) 
±7 days 
(Day 84-98) 
-14/ +30 days 
(Day 77-121) 
NA 
5 
Month 6 
(Day 181) 
±7 days 
(Day 174-188) 
-14/ +30 days 
(Day 167-211) 
-14/+30 days 
(Day 167-211) 
6 
Month 9 
(Day 271) 
±7 days 
(Day 264-278) 
-14/ +14 days 
(Day 257-285) 
-14/ +60 days 
(Day 257-331)c 
7 
Month 3E 
(Day 91E) 
±7 days 
(Day 84E-98E) 
-14/ +30 days 
(Day 77E-121E) 
NA 
8 
Month 6E 
(Day 181E) 
±7 days 
(Day 174E-188E) 
-14/ +30 days 
(Day 167E-211E) 
NA 
9 
Month 9E 
(Day 271E) 
±7 days 
(Day 264E-278E) 
-14/ +30 days 
(Day 257E-301E) 
-14/ +30 days 
(Day 257E-301E) 
10 
Month 12E 
(Day 361E) 
±7 days 
(Day 354E-368E) 
-14/ +30 days 
(Day 347E-391E) 
NA 
11 
Month 15E 
(Day 451E) 
±7 days 
(Day 444E-458E) 
-14/ +30 days 
(Day 437E-481E) 
-14/ +30 days 
(Day 437E-481E) 
12 
Month 21E 
(Day 631E) 
±7 days 
(Day 624E-638E) 
-14/ +30 days 
(Day 617E-661E) 
NA 
13 
Month 27E 
(Day 811E) 
±7 days 
(Day 804E-818E) 
-14/ +30 days 
(Day 797E-841E) 
-14/ +30 days 
(Day 797E-841E) 
14 
Month 33E 
(Day 991E) 
±7 days 
(Day 984E-998E) 
-14/ +30 days 
(Day 977E-1021E) 
NA 
15 
Month 39E 
(Day 1171E) 
±7 days 
(Day 1164E-1178E) 
-14/ +30 days 
(Day 1157E-1201E) 
-14/ +30 days 
(Day 1157E-1201E) 
16 
Month 45E 
(Day 1351E) 
±7 days 
(Day 1344E-1358E) 
-14/ +30 days 
(Day 1337E-1381E) 
NA 
17 
Month 51E 
(Day 1531E) 
±7 days 
(Day 1524E-1538E) 
-14/ +30 days 
(Day 1517E-1561E) 
-14/ +30 days 
(Day 1517E-1561E) 
a. 
These are the same as the windows in the protocol SoA (Section 1.3). 
b. Laboratory results must be received and reviewed by the investigator within 14 days after they are 
collected to determine eligibility to continue dosing. In addition, laboratory test results from the previous 


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Table 4. 
Windows for Remote Visits, Laboratory Sample Collections, and Special 
Safety Assessments if Required due to Public Emergencies Including 
COVID-19 
 
Visit 
Identifier 
Visit Month 
(Day in Study) 
Remote Visit 
Window 
(Day in Study)a 
Lab Collection 
Window 
(Day in Study)b 
Special Safety 
Assessment Window 
(Day in Study)c 
visit must be available and reviewed by the investigator prior to shipping investigational product at the 
current visit. 
c. 
The visit window for the on-site visit (Special Safety Assessments) for Month 9 is -7/+60 days and 
(Section 10.9.4). During TP3, the only special safety assessment is the audiological assessment. 
10.9.3.2. Electrocardiograms 
If the participant is unable to visit the study site for an ECG after the Screening visit, the 
participant may visit an alternative facility, or alternatively in the participant’s home, if 
available, to have the ECG performed according to the guidelines in Section 8.2.4. Qualified 
study site personnel must order, receive, and review results. For participants in TP3, ECG 
will not be recorded. 
10.9.3.3. Audiological and Neurological Specialist Evaluations 
At visits after Screening which require audiological or neurological evaluation, if the 
participant is unable to visit the designated ancillary center for audiological or neurological 
evaluation, the audiological history (Part 1 in the Audiometry Guide Worksheet for Post Day 
1 visits) and neurological history (General Neurology and Neuropathy Assessment 
Completion Guidelines) must be collected at the study site; during the remote visit per 
Section 10.9.2; or during the home health visit per Section 10.9.6. Clinically significant 
changes should be recorded as AEs in CRF. The audiological evaluations, including the 
BAEP, and the neurological evaluations must be performed per Section 8.2.6 at the next 
available opportunity, even if outside of the protocol-specified visit window. Only the 
audiological evaluation is collected during TP3. 
10.9.3.4. Skin Biopsies 
At visits after Day 1 which require a skin biopsy, if the participant is unable to visit the study 
site, then the skin biopsy must be performed at the next available opportunity, even if outside 
of a protocol-specified visit window. Not collected during TP3. 
10.9.4. Month 9 Visit Window 
The visit window for the special safety assessments at Month 9 in the setting of a public 
health emergency is expanded to -7 / +60 days. The usual safety assessments are to be 
completed as above. The full month 9 visit including the special safety assessments 
(audiological evaluations, neurological evaluation, and the skin biopsy) have until +60 days 
to be completed onsite or at the designated ancillary center. If required Special Safety 
Assessments (Section 10.9) cannot be performed at Month 9, the participant will not be 
allowed into the active therapy extension phase and must follow Early Termination 
procedures (Section 7.1). 


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Double-blind investigational product is dispensed until all the specialized safety assessments 
have been completed. The site staff should contact the IMPALA Help Desk for assistance. 
Active therapy investigational product is dispensed only after all the special safety 
assessments have been completed and is the start of the extension portion of the study. 
10.9.5. Study Intervention 
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered. 
Study intervention may be shipped by courier to study participants if permitted by local 
regulations and in accordance with storage and transportation requirements for the study 
intervention. Pfizer does not permit the shipment of study intervention by mail. The tracking 
record of shipments and the chain of custody of study intervention must be kept in the 
participant’s source documents/medical records. 
If a third-party courier engaged by Pfizer or Pfizer’s contract research organization (CRO) is 
used for shipping the study intervention, written consent must be documented in the 
informed consent document prior to shipping study intervention. If a third-party courier 
engaged by Pfizer or Pfizer’s CRO is not used for shipping the study intervention, consent 
must be verbally obtained (or per local guidelines/regulations) and documented in site’s 
source documents prior to shipping study intervention. 
Prior to shipping study intervention to a participant, 1) consent must be obtained and 
documented as described above, 2) all required safety information listed in Section 10.9.2. 
must have been collected and reviewed by the investigator, 3) the required laboratory tests 
from the previous visit must have been reviewed by the investigator, and 4) any additional 
evaluation (if requested based on investigator judgment) must have been performed, with 
results submitted to and reviewed by the investigator. 
Study intervention cannot be shipped to the participant and must be temporarily discontinued 
if 1) the laboratory tests from the previous visit have not been reviewed by the investigator 
OR 2) after reviewing the required information (including that from a remote visit), the 
investigator cannot make an assessment of whether it is safe for the participant to continue 
study intervention. Refer to Section 6.4 regarding temporary withholding of study 
intervention. 
The study site may deliver the study intervention to participants using an acceptable delivery 
method only if this is consistent with local laws and regulations and the site is able to ship the 
study intervention according to the guidelines provided by the Sponsor in a separate 
document. 
The amount of study intervention to be shipped should correspond to the amount dispensed 
per the Impala Quick Reference Guide at the specific study visit which is being conducted 


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remotely. Dispensing and/or shipment of additional study intervention to extend the visit 
window is not permitted. 
Participants should continue taking the current supply of study intervention until the new 
supply is received (unless temporary withholding of study intervention is required). 
Dosing logs should be shipped with the study intervention. 
Study sites should follow up with the participant once the study intervention is received by 
the participant to review when to start using the new blister cards or the new bottles (TP3 
only), the dosing instructions, and completion of the dosing logs. 
Participants should be instructed not to re-use or dispose of any blister cards, or bottles (TP3 
only) dispensed at a previous visit. 
All blister cards, or bottles (TP3 only) and dosing logs must be returned to the study site at 
the next on-site visit. 
10.9.6. Home Health Visits 
If available, a home health care service may be utilized to facilitate scheduled visits per the 
SoA (Section 1.3) if operationally feasible and will be conducted according to local 
regulations. Home health visits include a healthcare provider conducting an in-person study 
visit at the participant’s location, rather than an in-person study visit at the site. 
If a third-party engaged by Pfizer or Pfizer’s CRO is used for home health visits, written 
consent must be documented in the ICD prior to conducting the first home health visit. If a 
third-party engaged by Pfizer or Pfizer’s CRO is not used for home health visits, consent 
must be verbally obtained and documented in site’s source documents (or per local 
guidelines/regulations) prior to conducting the first home health visit. 
The C-SSRS, SALT, and PGI-C cannot be assessed at a home visit. 
The following may be performed during a home health visit: 
• Review dosing logs and record study intervention, including doses taken and any 
interruptions in intake of study intervention (ie, missed doses) since the last contact, 
and calculate compliance. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.3. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
• For WOCBP: Review and record contraceptive method and results 
of pregnancy testing. Confirm that the participant is adhering to the contraception 
method(s) required in the protocol (Section 10.4). Refer to Section 8.2.13 of the 
protocol and Section 10.9.3.1 regarding pregnancy tests. 


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• Collection of updated audiological history (Part 1 in the Audiometry Guide 
Worksheet for Post Day 1 visits) at visits requiring audiological evaluation. with 
entry of clinically significant changes onto the AE section of the eCRF, as 
appropriate. 
• Collection of interim neurological history (using General Neurology and Neuropathy 
Assessment Completion Guidelines) must be obtained, with entry of clinically 
significant changes onto the AE section of the eCRF, as appropriate. 
• Body temperature and collection method (eg, oral, tympanic, axillary), pulse rate, and 
respiratory rate (measured by study participant/caregiver). 
• ECG per Section 8.2.4 (only up to Month 15E). 
• Hematology. 
• Serum chemistry (CK only up to Month 15E ). 
• Lipid panel (for visits on or before Month 15E). 
• Urinalysis. (for visits after Month 15E, urinalysis will be performed only if 
considered clinically indicated by the investigator) 
• Pregnancy testing (for WOCBP). 
• Physical examination. 
10.9.7. Adverse Events and Serious Adverse Events 
If a participant has a confirmed or suspected COVID-19 infection during the study, this 
should be reported as an adverse event (AE) or serious adverse events (SAE) and appropriate 
medical intervention provided. For non-serious COVID-19 infections, temporary 
discontinuation of the investigational product may be medically appropriate until the 
participant has recovered from the COVID-19 infection. If this is a serious infection (ie, 
requires parenteral antimicrobial therapy or hospitalization for treatment or meeting other 
criteria that require the infection to be classified as a serious adverse event), the participant 
must be permanently discontinued from investigational product per Section 10.7.2 of the 
protocol. 
10.9.8. Efficacy Assessments 
The SALT and PGI-C (Section 8.1.2 and Section 8.1.3) are only to be collected during on- 
site visits. 


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10.10. Appendix 10: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
AA 
alopecia areata 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AT 
alopecia totalis 
AU 
alopecia universalis 
AUC 
area under the concentration-time curve 
BAEP 
brainstem auditory evoked potential 
BCR 
B cell receptor 
BMX 
bone marrow tyrosine kinase on chromosome X 
BP 
blood pressure 
BTK 
Bruton’s tyrosine kinase 
CFB 
change from baseline 
CFP-10 
culture filtrate protein 10 kiloDalton 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
Cmax 
maximum plasma concentration 
COE 
cross-over extension 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease-2019 
CRF 
case report form 
CRO 
Contract Research Organization 
CRU 
Clinical Research Unit 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CT 
clinical trial 
CXR 
chest radiograph 
CYP 
cytochrome P450 
dB 
decibels 
DDI 
drug-drug interaction 
DILI 
drug-induced liver injury 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
DNCB 
1-chloro-2,4-dinitrobenzene 
DPCP 
diphenylcyclopropenone 
E 
Active therapy extension phase 
EBA 
eyebrow assessment 


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Abbreviation 
Term 
EBV 
Epstein-Barr virus 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
E-DMC 
external data monitoring committee 
EDP 
exposure during pregnancy 
eGFR 
estimated glomerular filtration rate 
ELA 
eyelash assessment 
ELISA 
enzyme-linked immunosorbent assay 
EMA 
European Medicines Agency 
EOP 
end of placebo-controlled phase/beginning of active therapy 
extension phase 
EOS 
end of study 
EOT 
end of treatment 
ESAT-6 
early secreted antigenic target of 6 kiloDalton 
ET 
early termination 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FACS-TBNK 
fluorescence-activated cell sorting for T-cells, B-cells, and natural 
killer cells 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HBVDNA 
hepatitis B virus deoxyribonucleic acid 
HCVAb 
hepatitis C antibody 
HCV RNA 
hepatitis C virus ribonucleic acid 
HEENT 
head, eyes, ears, nose, and throat 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRQoL 
health-related quality of life 
HRT 
hormone replacement therapy 
IB 
Investigator’s Brochure 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ID 
identification 
IEC 
Independent Ethics Committee 
IENF 
intraepidermal nerve fiber 
IENFD 
intraepidermal nerve fiber density 
IFN 
interferon 


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Abbreviation 
Term 
Ig 
immunoglobulin 
IL 
interleukin 
IMPALA 
name of Pfizer’s interactive voice response system 
IND 
investigational new drug application 
INH 
isoniazid 
INR 
international normalized ratio 
IP-10 
interferon gamma-induced protein 10 
IRB 
institutional review board 
IRT 
interactive response technology 
ITK 
interleukin 2 inducible T cell kinase 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
IVRS 
interactive voice response system 
IWRS 
interactive web response system 
JAK 
Janus kinase 
LFT 
liver function test 
LTE 
long term extension 
MMF 
mycophenolate mofetil 
MMR 
measles, mumps, rubella 
MRI 
magnetic resonance imaging 
mRNA 
messenger ribonucleic acid 
MTX 
methotrexate 
NA 
not applicable 
NK 
natural killer 
NOAEL 
no observed adverse effect level 
NRS 
numerical rating scale 
PCD 
primary completion date 
PGI-C 
Patient’s Global Impression of Change 
PHQ-8 
Patient Health Questionnaire – 8 items 
PI 
principal investigator 
PK 
pharmacokinetics 
PN 
peripheral neuropathy 
PPD 
purified protein derivative 
PT 
prothrombin time 
PUVA 
Psoralen Ultraviolet A 
QD 
once daily 
QFT-G 
QuantiFERON-TB Gold In–tube test 
QoL 
quality of life 
QT interval 
time from the beginning of the QRS complex to the end of the 
T wave 
QTcF 
QT corrected using Fridericia’s correction factor 
RA 
rheumatoid arthritis 
RNA 
ribonucleic acid 


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Abbreviation 
Term 
SADBE 
squaric acid dibutylester 
SAE 
serious adverse event 
SALT 
Severity of Alopecia Tool 
SARS-CoV-2 
severe acute respiratory syndrome-coronavirus 2 
SBE 
single-blind extension 
SoA 
Schedule of Activities 
SOP 
standard operating procedure 
SRSD 
single reference safety document 
STAT 
signal transducer and activator of transcription 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TBili 
total bilirubin 
TCR 
T cell receptor 
TdP 
Torsades de pointes 
TEAE 
treatment-emergent adverse event 
TEC 
tyrosine kinase expressed in hepatocellular carcinoma 
TESAE 
treatment emergent serious adverse event 
TH1 
type 1 helper 
TP 
Treatment Period 
T-Spot test 
T-SPOT.TB 
TXK 
tyrosine kinase expressed in T cells 
TYK2 
tyrosine kinase 2 
US 
United States 
ULN 
upper limit of normal 
UVB 
Ultraviolet B 
WOCBP 
woman of childbearing potential 


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10.11. Appendix 11: Protocol Amendment 1 History 
 
Document History 
Document 
Version Date 
Summary and Rationale for Changes 
Amendment 1 
23 April 2021 
• 
In the Schedule of Activities for Screening and Day 
1, “Audiological evaluation and history by an 
audiologist” the name of the Audiology Study Guide 
was updated. 
Rationale: it was updated to its finalized name. 
• 
In the Schedule of Activities for the Intervention 
Period, the header note in the table (Row 4/Column 
11) was updated per the PACL 25 Jun 2020. 
Rationale: updated per the PACL and for clarity. 
• 
In the Schedule of Activities for the Intervention 
Period, “Audiological Evaluation by an audiologist” 
the name of the Audiology Study Guide was updated 
to its finalized name. 
Rationale: it was updated to its finalized name. 
• 
In the Schedule of Activities for the Intervention 
Period, “Pregnancy test” Notes were updated to 
enable pregnancy tests for outside testing to be 
provided by the site. 
Rationale: Enables testing for pregnancy between 
visits with a test at appropriate level of accuracy. 
• 
In the Schedule of Activities for the Intervention 
Period / Month 6 and Month 9/EOP, added a note 
that for the EOP visit only (Month 6 or Month 
9/EOP, as appropriate), the window for 
audiological/BAEP central read (including any 
repeat assessments if deemed necessary by the 
central reader) is -7/+21 days. All other assessments, 
including the primary audiological/BAEP 
assessments, must be completed within ±7 days. 
Rationale: Allows for audiological/BAEP central 
read and any repeats. 
• 
In the Schedule of Activities for the Intervention 
Period / Skin punch biopsy for evaluation of axonal 
dystrophy and IENFD, a note was added that at the 
EOP visit (Month 6 or Month 9, as appropriate), the 
skin biopsy must be collected before Active Therapy 
administration. 
Rationale: Ensures that secondary safety 
evaluations are completed prior to the start of 
active therapy extension phase. 
• 
In the Schedule of Activities for the Intervention 
Period, Study Intervention Dispensing Notes were 
updated to clarify that at the Month 6 visit (only for 
those eligible participants who enter the active 
therapy extension phase at Month 6 [see Section 
4.1.]) or 9/EOP visit, if the neurological or 
audiological/BAEP assessments have not yet been 
completed, double-blind therapy continues to be 
dispensed until the neurological and 
audiological/BAEP assessments (including the 


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Version Date 
Summary and Rationale for Changes 
central read confirmation and any repeat assessments 
if deemed necessary by the central reader) are 
completed. Active therapy is dispensed (via on-site 
visit or shipping) only once all the above procedures 
are completed. Refer to the IRT reference manual for 
dispensing additional double-blind therapy. 
Rationale: Ensures that primary and secondary 
safety evaluations are completed prior to the start 
of active therapy extension phase. 
• 
In the Schedule of Activities for the Intervention 
Period, “Home pregnancy test” section added. 
Rationale: Present in protocol but absent from 
SoA. 
• 
In the Schedule of Activities for Early Termination 
and Follow-up, header note (Row 2/Column 3) 
footnote added that there is no Visit 12 
Rationale: Footnote added to affirm that it is 
absent. 
• 
In the Schedule of Activities for Early Termination 
and Follow-up, “Audiological Evaluation”, the name 
of the Audiology Study Guide was updated to its 
finalized name. 
Rationale: it was updated to its finalized name. 
• 
In Section 4.1 Study Design, Overall Design, the 
ability to add participants due to issues related to 
peripheral nerve punch biopsy integrity, if needed 
was added. 
Rationale: Approximately 60 participants are to 
have interpretable peripheral nerve punch 
biopsies. 
• 
In Section 4.1, statement added “The skin biopsy 
must be collected before the start of Active Therapy 
Extension Phase.” 
Rationale: Ensures that secondary safety 
evaluations are completed prior to the start of 
active therapy extension phase. 
• 
In Section 5.1 Inclusion criterion 2, clarified that the 
central reader must confirm that the participant has 
normal hearing prior to randomization. 
Rationale: Clarified based on questions from site 
staff. 
• 
In Section 5.2. Exclusion Criteria, Medical 
Conditions, 1, actions in response to C-SSRS 
responses were clarified 
Rationale: Clarified based on questions in similar 
studies. 
• 
In Section 5.2. Exclusion Criteria, Medical 
Conditions, 21b, added recommended CXR views. 
Rationale: Added to align with description in 
Section 8.2.3. 
• 
In Section 5.2. Exclusion Criteria, Prohibited 
Prior/Concomitant Therapy, 22e, clarified wording 


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Document 
Version Date 
Summary and Rationale for Changes 
Rationale: Clarified in response to questions from 
Investigators. 
• 
Section 5.2. Exclusion Criteria, Prohibited 
Prior/Concomitant Therapy, 22, on QT prolonging 
drugs removed. 
Rationale: An analysis of applicable nonclinical 
and clinical data indicates that the risk for PF- 
06651600 to cause clinically meaningful QT 
prolongation in humans is low. Prohibition of 
these medications is no longer required. 
• 
Section 5.2 Exclusion Criteria, 23, Updated to 
clearly exclude participation in investigational 
vaccine trials. 
Rationale: Update explicitly excludes concurrent 
participation in studies of investigational 
vaccines. 
• 
Section 6.2.1. Preparation and Dispensing was 
updated to add that at the EOP visit (Month 6 or 
Month 9/EOP, as appropriate), additional double- 
blind therapy may be dispensed if the neurological 
and/or audiological/BAEP assessments (including 
the central read confirmation and any repeat 
assessments if deemed necessary by the central 
reader) are not yet completed. Additional double- 
blind therapy would be dispensed as a 32-day 
supply, but dosing may not extend past the end of the 
+21 day EOP visit window. Once neurological and 
audiological/BAEP EOP assessments are complete, 
active therapy may be dispensed either on site or by 
shipping to the study participant. 
Rationale: Allows continued double-blind dosing 
until safety assessments are completed, within a 
defined window (+21 days). 
• 
Section 6.5.3. Vaccinations, was updated given the 
widespread use of vaccines against COVID-19 
Rationale: This change was made to provide 
affirmatory clarity regarding COVID-19 
vaccination before, during, and after the study. 
• 
Section 8.2.6. Audiological Evaluations, clarification 
that the central reader reviews the audiological 
results. 
Rationale: To provide clarity for study sites. 
• 
Section 8.2.6. Audiological Evaluations, the name of 
the Audiology Study Guide was updated. 
Rationale: it was updated to its finalized name. 
• 
Section 8.2.7. Brainstem Auditory Evoked Potential 
Evaluations removed “local” from the definition of 
which results are used for analysis. 
Rationale: Clarifies that only results which have 
undergone central read are used for analysis. 
• 
Section 8.2.9.2.2 Canfield Rash Manual updated to 
Canfield Photography User Manual. 


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Version Date 
Summary and Rationale for Changes 
Rationale: name as written was incorrect. 
• 
Section 8.2.10.1.3. Subsequent Tuberculosis Testing, 
was updated regarding actions to be taken in the 
event of a positive result in an ongoing participant. 
Rationale: Updated to include evaluation by local 
specialists. 
• 
In Section 8.2.11.1. Columbia Suicide Severity 
Rating Scale (C-SSRS), actions in response to C- 
SSRS responses were clarified in alignment with 
exclusion criterion 1. 
Rationale: Updated for greater clarity. 
• 
Section 8.2.14. The name of the ‘Rater 
Qualifications Manual’ was updated to ‘Rater 
Assessment Manual’ 
Rationale: It was updated to its finalized name. 
• 
Section 8.3.6. Cardiovascular and Death Events, was 
updated to reflect the adjudication process 
Rationale: Reference to the adjudication was 
added. 
• 
Section 8.3.8. Adverse Events of Special Interest, 
was updated to add a reference to the section with 
the definition and the reporting process. 
Rationale: This was updated for clarity. 
• 
Section 8.10. Health Economics, was deleted 
Rationale: This section was deleted as per PACL 
25 Jun 2020. 
• 
Section 10.4. Appendix 4: Contraceptive Guidance 
and Collection of Pregnancy Information, was 
updated to remove the word ‘adolescents’. 
Rationale: There are no adolescents in this study. 
• 
Section 10.6. Appendix 6. Reference for Global 
Prevalence of Hepatitis B virus infection changed to 
footnote from in-line text. 
Rationale: for consistency of style. 
• 
Section 10.7.1. Monitoring, a footnote was added to 
the table in reference to the timeframe for re-testing 
Rationale: This was updated to reflect that the 
timeframe depends on the timing of the 
awareness of the abnormal result. 
• 
Section 10.7.2. Monitoring, Laboratory 
Abnormalities a second sentence was added 
regarding the timeframes for retesting 
Rationale: This was updated to reflect that the 
timeframe depends on the timing of the 
awareness of the abnormal result. 
• 
Section 10.7.2. Monitoring, Discontinuation/End of 
Treatment Monitoring, bullet 2, the name of the 
Audiology Study Guide was updated. 
Rationale: it was updated to its finalized name. 
• 
Section 10.9. Appendix 9: Alternative Measures 
During Public Emergencies, was added to permit the 
study to continue during a health emergency. 


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Document History 
Document 
Version Date 
Summary and Rationale for Changes 
Rationale: Added to permit the study to continue 
while maintaining treatment continuity and safety 
oversight. 
• 
Throughout document: administrative 
changes. 
Rationale: Added for clarity, internal 
consistency, and grammatical 
correctness. 
Original 
protocol 
08 May 2020 
N/A 


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11. REFERENCES 
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Gilhar, A, Etzioni, A, Paus, R. Alopecia areata. N Engl J Med. 2012;366(16):1515- 
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NAAF website. NAAF website at https://www.naaf.org/alopecia-areata/alopecia- 
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Hunt, N, McHale, S. The psychological impact of alopecia. BMJ. 
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McGarvey, EL, Baum, LD, Pinkerton, RC, et al. Psychological sequelae and alopecia 
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Colon, EA, Popkin, MK, Callies, AL, et al. Lifetime prevalence of psychiatric 
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Ruiz-Doblado, S, Carrizosa, A, Garcia-Hernandez, MJ. Alopecia areata: psychiatric 
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Chen, W, Mempel, M, Traidl-Hofmann, C, et al. Gender aspects in skin diseases. J 
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Villasante Fricke, AC, Miteva, M. Epidemiology and burden of alopecia areata: a 
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Liakopoulou, M, Alifieraki, T, Katideniou, A, et al. Children with alopecia areata: 
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Dubois, M, Baumstarck-Barrau, K, Gaudy-Marqueste, C, et al. Quality of life in 
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Masmoudi, J, Sellami, R, Ouali, U, et al. Quality of life in alopecia areata: a sample 
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de Hollanda, TR, Sodre, CT, Brasil, MA, et al. Quality of life in alopecia areata: a 
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Baghestani, S, Zare, S, Seddigh, SH. Severity of Depression and Anxiety in Patients 
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Jankovic, S, Peric, J, Maksimovic, N, et al. Quality of life in patients with alopecia 
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Rencz, F, Gulacsi, L, Pentek, M, et al. Alopecia areata and health-related quality of 
life: a systematic review and meta-analysis. Br J Dermatol. 2016;175(3):561-71. 


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21. 
Zhang, M, Zhang, N. Quality of life assessment in patients with alopecia areata and 
androgenetic alopecia in the People's Republic of China. Patient Prefer Adherence. 
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Hordinsky, MK. Current Treatments for Alopecia Areata. J Investig Dermatol Symp 
Proc. 2015;17(2):44-6. 
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Hordinsky, M, Donati, A. Alopecia areata: an evidence-based treatment update. Am J 
Clin Dermatol. 2014;15(3):231-46. 
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Alkhalifah, A, Alsantali, A, Wang, E, et al. Alopecia areata update: part II. 
Treatment. J Am Acad Dermatol. 2010;62(2):191-202, quiz 3-4. 
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Messenger, AG, McKillop, J, Farrant, P, et al. British Association of Dermatologists' 
guidelines for the management of alopecia areata 2012. Br J Dermatol. 2012;166(5):916-26. 
26. 
Delamere, FM, Sladden, MM, Dobbins, HM, et al. Interventions for alopecia areata. 
Cochrane Database Syst Rev. 2008(2):CD004413. 
27. 
Gilhar, A. Collapse of immune privilege in alopecia areata: coincidental or 
substantial? J Invest Dermatol. 2010;130(11):2535-7. 
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Bertolini, M, Zilio, F, Rossi, A, et al. Abnormal interactions between perifollicular 
mast cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata. PLoS 
One. 2014;9(5):e94260. 
29. 
Guttman-Yassky, E, Ungar, B, Noda, S, et al. Extensive alopecia areata is reversed by 
IL-12/IL-23p40 cytokine antagonism. J Allergy Clin Immunol. 2016;137(1):301-4. 
30. 
Fuentes-Duculan, J, Gulati, N, Bonifacio, KM, et al. Biomarkers of alopecia areata 
disease activity and response to corticosteroid treatment. Exp Dermatol. 2016;25(4):282-6. 
31. 
Xing, L, Dai, Z, Jabbari, A, et al. Alopecia areata is driven by cytotoxic T 
lymphocytes and is reversed by JAK inhibition. Nat Med. 2014;20(9):1043-9. 
32. 
Kennedy Crispin, M, Ko, JM, Craiglow, BG, et al. Safety and efficacy of the JAK 
inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. 
33. 
Craiglow, BG, King, BA. Killing two birds with one stone: oral tofacitinib reverses 
alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol. 2014;134(12):2988- 
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34. 
Jabbari, A, Dai, Z, Xing, L, et al. Reversal of Alopecia Areata Following Treatment 
With the JAK1/2 Inhibitor Baricitinib. EBioMedicine. 2015;2(4):351-5. 
35. 
Harris, JE, Rashighi, M, Nguyen, N, et al. Rapid skin repigmentation on oral 
ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad 
Dermatol. 2016;74(2):370-1. 
36. 
Mackay-Wiggan, J, Jabbari, A, Nguyen, N, et al. Oral ruxolitinib induces hair 
regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 
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King, BA, editor Treating alopecia areeata, vitiligo, and atopic dermatitis: JAK 
inhibitors, something new for dermatology. Am Acad Dermatol Scientific Meeting; 19 Feb 
2018. 
38. 
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39. 
Liu, LY, Craiglow, BG, Dai, F, et al. Tofacitinib for the treatment of severe alopecia 
areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017;76(1):22-8. 
40. 
Berg, LJ, Finkelstein, LD, Lucas, JA, et al. Tec family kinases in T lymphocyte 
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Schwartzberg, PL, Finkelstein, LD, Readinger, JA. TEC-family kinases: regulators of 
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symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an 
evidence-based review). Report of the American Academy of Neurology, American 
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47. 
Lauria, G, Bakkers, M, Schmitz, C, et al. Intraepidermal nerve fiber density at the 
distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15(3):202-7. 
48. 
Valentine, WM. Toxic Peripheral Neuropathies: Agents and Mechanisms. Toxicol 
Pathol. 2019:192623319854326. 
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oxaliplatin-induced neuropathy. Neurology. 2011;77(10):980-6. 
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Khoshnoodi, MA, Truelove, S, Burakgazi, A, et al. Longitudinal Assessment of Small 
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Wyrwich, KWKH, Knight S. et al. The Role of Patients in the Development of the 
Alopecia Areata Investigator Global Assessment (AA-IGA), a Clinican-Reported Measure 
Evaluating Clinically Meaningful Success in Clinical Trials. Alopecia Areata Research 
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52. 
Olsen, EA. Investigative guidelines for alopecia areata. Dermatol Ther. 
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Posner, K, Oquendo, MA, Gould, M, et al. Columbia Classification Algorithm of 
Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric 
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55. 
Kroenke, K, Spitzer, RL. The PHQ-9: A new depression diagnostic and severity 
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Chan, IS, Zhang, Z. Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics. 1999;55(4):1202-9. 

SAP_003.pdf: 
Protocol B7981037 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
 
 
 
 
 
Protocol B7981037 
 
 
 
 
 
 
 
 
A PHASE 2a, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY INVESTIGATING THE SAFETY OF RITLECITINIB (PF-06651600) IN 
ADULT PARTICIPANTS WITH ALOPECIA AREATA 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version: 
5.0 
Date: 
04 April, 2023 


Protocol B7981037 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 2 
 
 
TABLE OF CONTENTS 
LIST OF TABLES ..................................................................................................................... 4 
LIST OF FIGURES .................................................................................................................... 4 
1. VERSION HISTORY ............................................................................................................ 5 
2. INTRODUCTION .................................................................................................................. 7 
2.1. Study Objectives, Endpoints, and Estimands ............................................................ 7 
2.2. Study Design .............................................................................................................. 9 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................. 12 
3.1. Primary Endpoint – Safety in TP1 ........................................................................... 12 
3.2. Secondary Endpoints – Safety in TP1+TP2 ............................................................ 12 
3.3. Secondary Endpoints – Efficacy in TP1+TP2 ......................................................... 13 
3.4. Exploratory Endpoints – Efficacy in TP3 ................................................................ 13 
3.5. Baseline Variables ................................................................................................... 13 
3.6. Safety Endpoints ...................................................................................................... 13 
3.6.1. Adverse Events ........................................................................................... 13 
3.6.2. Laboratory Data .......................................................................................... 15 
3.6.3. Electrocardiogram (ECG) ........................................................................... 15 
3.6.4. Vital Signs, including Height and Weight ................................................... 15 
3.6.5. Physical Examinations ................................................................................ 15 
4. ANALYSIS SETS ................................................................................................................ 16 
5. GENERAL METHODOLOGY AND CONVENTIONS .................................................... 16 
5.1. Hypotheses and Decision Rules .............................................................................. 16 
5.2. General Methods ...................................................................................................... 16 
5.3. Methods to Manage Missing Data ........................................................................... 17 
6. ANALYSES AND SUMMARIES ....................................................................................... 17 
6.1. Primary Endpoint ..................................................................................................... 17 
6.2. Secondary Endpoints-Safety .................................................................................... 18 
6.2.1. I-V Interwave Latency on BAEP ................................................................ 18 
6.2.2. Percentage of IENF with Axonal Swellings in Skin Punch Biopsies ......... 18 
6.2.3. IENFD in Skin Punch Biopsies ................................................................... 18 
6.2.4. Amplitude of Wave V on BAEP ................................................................. 18 
6.2.5. Absence of Wave V on BAEP .................................................................... 19 


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6.2.6. Incidence of Treatment-emergent Adverse Events (TEAEs) ...................... 19 
6.2.7. Incidence of Treatment-emergent Serious Adverse Events (TESAEs) ....... 19 
6.2.8. Incidence of Adverse Events (AEs) Leading to Discontinuation ................ 19 
6.2.9. Incidence of Clinically Significant Abnormalities in ECG (only 
QTcF) and Vital Signs ...................................................................................... 19 
6.2.10. Incidence of Clinically Significant Abnormalities in Clinical 
Laboratory Values ............................................................................................ 20 
6.3. Secondary and exploratory Endpoints-Efficacy ...................................................... 20 
6.3.1. Overall and AA SALT Scores .................................................................... 20 
6.3.2. PGI-C Response .......................................................................................... 21 
6.4. Other Endpoints ....................................................................................................... 21 
6.5. Subset Analyses ....................................................................................................... 21 
6.6. Baseline and Other Summaries and Analyses .......................................................... 21 
6.6.1. Baseline Summaries .................................................................................... 21 
6.6.2. Study Conduct and Subject Disposition ...................................................... 21 
6.6.3. Study Treatment Exposure .......................................................................... 21 
6.6.4. Concomitant Medications and Non-Drug Treatments ................................ 22 
6.6.5. Alopecia areata history ............................................................................... 22 
6.7. Safety Summaries and Analyses .............................................................................. 22 
6.7.1. Adverse Events ........................................................................................... 23 
6.7.2. Laboratory Data .......................................................................................... 23 
6.7.3. Vital Signs ................................................................................................... 23 
6.7.4. Electrocardiogram ....................................................................................... 23 
7. INTERIM ANALYSES ....................................................................................................... 24 
8. TIMING AND TREATENT GROUPS DISPLAYED FOR EACH ANALYSIS ............... 24 
8.1. PCD-CSR ................................................................................................................. 24 
8.2. Supplemental CSR 1 ................................................................................................ 25 
8.3. Supplemental CSR 2 ................................................................................................ 26 
9. ENDPOINTS INCLUDED IN EACH CSR ......................................................................... 26 
10. REFERENCES ................................................................................................................... 28 
11. APPENDICES .................................................................................................................... 29 
11.1. Appendix 1 Definition and Use of Visit Windows in Reporting ........................... 29 
11.2. Appendix 2 List of Countries by Region ............................................................... 30 


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11.3. Appendix 3 Study Days Used to Define Each Visit Period in the 
Calculation of By Visit Table for Compliance. ........................................................ 31 
 
 
LIST OF TABLES 
Table 1. 
Summary of Major Changes in SAP Amendments .................................... 5 
Table 2. 
Study Objectives and Endpoints ................................................................ 8 
Table 3. 
Groups ...................................................................................................... 24 
Table 4. 
Groups ...................................................................................................... 25 
 
 
LIST OF FIGURES 
Figure 1. 
Study Design Schematic ........................................................................... 11 


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1. VERSION HISTORY 
Table 1. 
Summary of Major Changes in SAP Amendments 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1.0 
05 Aug 2020 
Original 
8 May 2020 
Not Applicable 
Not Applicable 
2.0 
28 Sep 2021 
Amendment 1 
20 Apr 2021 
To match TLF 
Add abbreviations to the analysis 
set 
For clarification 
In section 5.2, elaborate the “Binary 
safety data” 
To assess the 
impact of 
COVID-19 
In section 6.7, add COVID-19 
related safety analysis 
For clarification 
Add appendix 2, list of countries for 
regions 
For clarification 
Add details to calculate cumulative 
dose/compliance by visit in Section 
6.6.3 and appendix 3 
ECG analysis was 
missing in version 
1 
Add ECG analysis in Section 6.2.9 
For clarification 
Added details to calculate 
cumulative dose and compliance in 
appendix 3. 
For clarification 
In section 7, specified only data up 
to Month 9 will be included in the 
analysis for PCD 
3.0 
22 Nov 2021 
Amendment 1 
20 Apr 2021 
For clarification 
In section 7, update the scope of 
PCD CSR, and unblinding/blinding 
status of sponsors, investigators and 
participants after PCD 
For clarification 
Insection 3.6.3, specified that only 
QTcF interval will be analyzed, 
instead of all ECG parameters 
Team decision 
Delete the analysis of physical 
examinations, C-SSRS, and 
cumulative dose up to each visit 
4.0 
17 Aug 2022 
Amendment 2 
28 Apr 2022 
Updated to 
incorporate 
changes in 
protocol 
amendment 2 
In section 2, updated the study 
objects and endpoints, study design 


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Table 1. 
Summary of Major Changes in SAP Amendments 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
Updated to 
incorporate 
changes in 
protocol 
amendment 2 
Added exploratory efficacy 
endpoints in section 3.4 
Clarify according 
to PCD CSR 
Add clarification in section 3.2 “For 
each participant, data were reported 
as the percentage of IENF with any 
number of swellings. The endpoint 
“axonal dystrophy” refers to the 
percentage of IENF with axonal 
swellings.”, similar in section 6.2.2 
” 
This analysis was 
added to the PCD 
CSR to assist with 
the interpretation 
of secondary 
endpoints 
In section 6.2.3, the following 
analysis was added, “Descriptive 
Summary of absolute and change 
from baseline in IENFD normalized 
by age and gender.” 
This analysis was 
was added to the 
PCD CSR to assist 
with the 
interpretation of 
the secondary 
endpoints 
In section 6.2.4 “percent change 
from baseline in amplitude of wave 
V on BAEP at a stimulus intensity 
of 80dB at Months 6, 9, 9E, and 
15E” was added 
Updated to 
incorporate 
changes in 
protocol 
amendment 2 
Section 8 and Section 9 were added 
to specify the timing of each 
analysis and the endpoints included 
in each CSR. 
Updated to 
incorporate 
changes in 
protocol 
amendment 2 
Section 11, the analysis visit 
window definition was updated to 
include TP3 
5.0 
04 April 
2023 
Amendment 2 
28 Apr 2022 
Update to include 
the definition of 
risk period for the 
purpose of 
summarizing 
Section 3.6.1, add the definitions of 
risk periods for the summaries of 
AEs. 


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Table 1. 
Summary of Major Changes in SAP Amendments 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
safety data. This 
update was made 
for consistency 
with the AA 
ritlecitinib 
program. 
clarified that the 
Overall column in 
binary summary 
tables will also 
include the 
observation period 
Section 8.2, Added table 4. 
Clarification of 
the statistical 
method used to 
analyze 
continuous 
endpoints 
Section 5.2. General methods. 
Remove ‘and subject as a random 
effect’, and add instructions on how 
to run the model in SAS in case of 
convergence issues. 
Clarification that 
the linear mixed- 
effects model 
includes not only 
the primary 
timepoint, but also 
other timepoints 
In Sections 6.1. and 6.2.1. added 
added ‘which includes all post- 
baseline measurements throught …’ 
to the statistical methods. 
Clarification of 
the statistical 
method used for 
the overall and 
AA SALT scores 
Section 6.3.1. Removed the details 
describing the linear mixed-effects 
model, 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study B7981037. 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, Endpoints, and Estimands 
The study objectives and corresponding endpoints are listed below in Table 2. Estimands are 
not applicable since there is no formal statistical hypothesis testing for this study. 


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Table 2. 
Study Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary – Safety 
• To assess I-V interwave 
latency on brainstem 
auditory evoked potentials 
(BAEPs) in adult 
participants with alopecia 
areata (AA) treated with 
PF-06651600. 
• Change from baseline in I-V interwave latency on 
BAEP at a stimulus intensity of 80 decibels (dB) 
at Month 9. 
Secondary – Safety 
• To assess I-V interwave 
latency on BAEPs in adult 
participants with AA 
treated with PF-06651600. 
• Change from baseline in I-V interwave latency on 
BAEP at a stimulus intensity of 80dB at 
Months 6, 9E, and 15E. 
• To assess axonal dystrophy 
in intraepidermal nerve 
endings over time in adult 
participants with AA 
treated with PF-06651600. 
• Change from baseline in axonal dystrophy in skin 
punch biopsies at Month 9 and Month 15E. 
• To assess intraepidermal 
nerve fiber density 
(IENFD) over time in adult 
participants with AA 
treated with PF06651600. 
• Change from baseline in IENFD in skin punch 
biopsies at Month 9 and Month 15E. 
• To assess wave V 
amplitude on BAEP over 
time in adult participants 
with AA treated with 
PF-06651600. 
• Change from baseline in amplitude of wave V on 
BAEP at a stimulus intensity of 80dB at Months 
6, 9, 9E, and 15E. 
• To assess presence of wave 
V on BAEP over time in 
adult participants with AA 
treated with PF-06651600. 
• Absence of wave V on BAEP at stimulus 
intensities ranging from 80dB to 40dB at 
Months 6, 9, 9E, and 15E. 
• To evaluate the safety and 
tolerability of PF-06651600 
in adult participants with 
AA. 
• Incidence of treatment emergent adverse events 
(TEAEs), treatment-emergent serious adverse 
events (TESAEs), and adverse events (AEs) 
leading to discontinuation;a 
• Incidence of clinically significant abnormalities in 
vital signs and ECG; a; 


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Table 2. 
Study Objectives and Endpoints 
 
Objectives 
Endpoints 
• Incidence of clinically significant abnormalities in 
clinical laboratory values. a 
Secondary – Efficacy TP1-TP2 
• To evaluate response to PF- 
06651600 measured by the 
Severity of Alopecia Tool 
(SALT) in adult 
participants with AA. 
• Change from baseline in overall and AA SALT 
score at Month 9 and other time points collected. a 
• To evaluate the response to 
PF-06651600 measured by 
the Patient’s Global 
Impression of Change 
(PGI-C) tool in adult 
participants with AA. 
• PGI-C score response defined as greatly improved 
or moderately improved from baseline at Month 9 
and other time points collected. 
Tertiary/Exploratory-Efficacy 
TP3 
• To evaluate long-term 
response to PF 06651600 
measured by the Severity of 
Alopecia Tool (SALT) in 
adult participants with AA. 
• Change from baseline in overall and AA SALTb 
score at Month 51E and other time points 
collected. 
• To evaluate the long-term 
response to PF-06651600 
measured by the Patient’s 
Global Impression of 
Change (PGI-C) tool in 
adult participants with AA. 
• PGI-C score response defined as greatly improved 
or moderately improved at Month 51E and other 
time points collected. 
a. 
Refer to Section 9 for specific safety summary included in each clinical study report 
b. AA SALT is the amount of scalp hair loss due to AA. 
2.2. Study Design 
This is a Phase 2a, randomized, double-blind, placebo-controlled safety study designed to 
evaluate the safety and tolerability of PF-06651600, including the assessments of BAEP and 
IENF, in adults 18 to ≤50 years of age with ≥25% scalp hair loss due to AA. 
Treatment Period 1 (TP1) and Treatment Period 2 (TP2): 
The total duration of participation in the study for TP1 and TP2 will be approximately 
26 months. 
This includes up to a 5-week screening period, a 9-month placebo-controlled 
treatment phase, a 15-month active therapy extension phase, and a 4-week follow-up 


Protocol B7981037 (PF-06651600) Statistical Analysis Plan 
 
period [for participants not continuing to TP3 or discontinuation of study 
intervention]. Screening will occur within 35 days prior to Day 1 of the study to 
confirm that selection criteria for the study are met. At Month 9, the placebo- 
controlled phase will end, and all participants may enter the active therapy extension 
phase of the study and receive PF- 06651600. For any participant discontinued for a 
neurological or auditory adverse event, the participant will be evaluated again at 6 
months after discontinuation; the maximum duration of participation in the study for 
such participants could be approximately 32 months if the event occurred at the last 
visit. 
Treatment Period 3 (TP3): 
The total duration for TP3 will be of variable length for individual participants; 
assuming a participant does not require discontinuation per protocol. A participant 
may continue to receive PF-06651600 in TP3 for a maximum of an additional 36 
months or until availability of commercial product in their country, or until the 
Sponsor terminates the study in that country, whichever occurs first. 
In TP3, participants will receive 50 mg QD PF-06651600. The total duration of 
participation in TP3 is approximately 37 months, including up to 36 months study 
intervention, and a follow up period of 4 weeks after completion or discontinuation of 
study intervention. 
Observation Period: 
If study intervention is permanently discontinued, the participant will be asked to 
remain in the study after the Follow-up visit without study intervention, and continue 
to comply with study visit schedules for approximately 2 years after the last dose of 
study intervention or until study end, whichever occurs first. 
A study design schematic is presented in Figure 1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol B7981037 (PF-06651600) Statistical Analysis Plan 
 
 
 
Figure 1. Study Design Schematic 
 
 
 
 
 
 
 
 
 
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Sample Size Determination 
Approximately 60 adults 18 to 50 years of age will be randomized in a 1:1 allocation ratio to 
either the PF-06651600 200 mg QD/50 mg QD dose group or the placebo group. 
For the primary safety endpoint, change from baseline in I-V interwave latency on BAEP at 
Month 9, the published standard deviations for I-V interwave latency on BAEP range from 
0.1 to 0.3 ms.1-3 Assuming a standard deviation of 0.2 ms, and assuming the standard 
deviation of change from baseline is similar to the standard deviation of actual score, the 
half-width of 95% confidence interval for the group will be 0.07 ms for 30 participants per 
group. 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint – Safety in TP1 
• Change from baseline in I-V interwave latency on BAEP at a stimulus intensity of 80 
decibels (dB) at Month 9. 
3.2. Secondary Endpoints – Safety in TP1+TP2 
• Change from baseline in I-V interwave latency on BAEP at a stimulus intensity of 
80dB at Months 6, 9E, and 15E; 
• Change from baseline in axonal dystrophy in skin punch biopsies at Month 9 and 
Month 15E; 
• For each participant, data was reported as the percentage of IENF with any 
number of swellings. The endpoint “axonal dystrophy” refers to the percentage of 
IENF with axonal swellings. 
• Change from baseline in IENFD in skin punch biopsies at Month 9 and Month 15E; 
• Change from baseline in amplitude of wave V on BAEP at a stimulus intensity of 
80dB at Months 6, 9, 9E, and 15E; 
• Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB at 
Months 6, 9, 9E, and 15E; 
• Incidence of treatmentemergent adverse events (TEAEs); 
• Treatment-emergent serious adverse events (TESAEs); 
• TEAEs leading to discontinuation; 
• Incidence of clinically significant abnormalities in vital signs and ECG; 
• Incidence of clinically significant abnormalities in clinical laboratory values. 


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3.3. Secondary Endpoints – Efficacy in TP1+TP2 
• Change from baseline in overall and AA SALT score at Month 9 and other time 
points collected in TP1 and TP2; 
• PGI-C score response defined as greatly improved or moderately improved from 
baseline at Month 9 and other time points collected in TP1 and TP2. 
3.4. Exploratory Endpoints – Efficacy in TP3 
• Change from baseline in overall and AA SALT score at Month 51E and other time 
points collected in TP3. 
• PGI-C score response defined as greatly improved or moderately improved at Month 
51E and other time points collected in TP3. 
3.5. Baseline Variables 
Baseline values will be defined as follows for both safety and efficacy endpoints: 
• Baseline is defined as the last non-missing measurement obtained before the first dose 
in the placebo-controlled phase. 
3.6. Safety Endpoints 
The primary and secondary safety endpoints are defined above in Section 3.1 and 
Section 3.2. 
3.6.1. Adverse Events 
• 
The following risk period (RP) will be applied for TP1 
• 
For patients who entered TP1 and continued into TP2, RP is defined from date of 1st 
dose of TP1 to min (date of 1st dose of TP2 - 1, date of the last dose of TP1 + 35). 
This RP excluded AEs starting on the same day of 1st dose of TP2 or AEs starting on 
any day in TP2. 
• 
For patients who entered in TP1, permanently discontinued from study (and did not 
enter in TP2), RP is defined from date of 1st dose of TP1 to min (date of last contact, 
date of the last dose of TP1 + 35), where last contact date is min (date of 
discontinuation of study, date of data cut-off), if a subject dies, the death date will be 
the last contact date. 
• 
The following risk period will be applied for TP2 
• 
For patients who entered TP2 and continued into TP3, RP is defined from date of 1st 
dose of TP2 to min (date of 1st dose of TP3 - 1, date of the last dose of TP2 + 35). 
This RP excludes AEs starting on the same day of 1st dose of TP3 or AEs starting on 
any day in TP3 


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• 
For patients who entered in TP2 and, directly entered in the Observation Period or 
permanently discontinued from study (and did not enter in TP3), RP is defined from 
date of 1st dose of TP2 to min (date of last contact, date of the last dose of TP2 + 
35), where last contact date is min (date of discontinuation of study, date of data cut- 
off), if a subject dies, the death date will be the last contact date. This RP extends 35 
days into the observation period. 
• 
The following RP will be applied for Observation Period for patients who entered from 
TP2 
• 
For patients who entered the observation period from TP2, RP is defined from date 
of last dose + 1 to the last contact date, where the last contact date is min (date of 
discontinuation of study, date of data cut-off). If a subject dies, the death date will be 
the last contact date. This RP excludes AEs starting wile on-drug. 
• 
The following RP will be applied for TP3 
• 
For patients who entered in TP3, RP is defined from date of 1st dose in TP3 to min 
(last contact date, last dose date + 35) where last contact date is max (date of 
discontinuation of study, date of subject’s last visit). In the case of an interim data 
cut, the last contact date is min (date of discontinuation of study, date of data cut- 
off). If a subject dies, the death date will be the last contact date. This RP includes 
AEs that occure within 35 days after the last dose 
• 
The following RP will be applied for Observation Period for patients who entered from 
TP3 
• 
For patients who entered the observation period from TP3, RP is defined from date 
of last dose + 1 to last contact date, where last contact date is max (date of 
discontinuation of study, date of subject’s last visit). In the case of an interim data 
cut, the last contact date is min (date of discontinuation of study, date of data cut- 
off). If a subject dies, the death date will be the last contact date. This RP excludes 
AEs starting while on-drug. 
• 
Supplemental CSR1 will include summaries of TEAEs as described in Table 4. 
• 
Supplemental CSR2 will include summaries of TEAEs for the RP defined for TP3, and 
for the RP defined for the Observation period for patients who entered from TP3. 


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3.6.2. Laboratory Data 
Below is a list of Laboratory Assessments to be performed at times specified in the schedule 
of activities in the protocol. 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
BUN and creatinine 
pH 
At screening or Day 1 
only: 
• FSH 
• Pregnancy test 
(β-hCG) 
• Hepatitis C antibody 
• HIV 
• HbA1C 
• HbsAg 
• HbcAb 
• HbsAb 
• HBVDNA 
• HCVAb 
• HCVRNA 
• QFT-G test or T-Spot 
test 
• Viral Screen 
• Fasting Lipid profile 
Hematocrit 
Glucose 
Glucose (qual) 
RBC count 
Calcium 
Protein (qual) 
%Reticulocytes 
Sodium 
Blood (qual) 
MCV 
Potassium 
Ketones 
MCH 
Chloride 
Nitrites 
Platelet count 
Total CO2 (bicarbonate) 
Leukocyte esterase 
WBC count 
AST, ALT 
Urobilinogen 
Neutrophils 
Total bilirubin 
Urine bilirubin 
Eosinophils 
Direct and Indirect bilirubin 
Microscopy 
Monocytes 
Alkaline phosphatase 
Urine culture 
Basophils 
Uric acid 
Lymphocytes 
Albumin 
Total protein 
Creatine Kinase 
Follow up testing for 
potential DILI cases 
3.6.3. Electrocardiogram (ECG) 
ECG measurements will be collected at screening, at the end of placebo-controlled phase and 
at the end of active therapy extension phase. 
3.6.4. Vital Signs, including Height and Weight 
Vital sign measurements are pulse rate, blood pressure, respiratory rate, and oral, tympanic or 
axillary temperature. They will be performed at times specified in the schedule of activities 
in the protocol. 
Height will be collected at screening and weight will be collected at both screening and 
baseline. Weight will be collected at the end of the placebo-controlled phase and at the end of 
the active therapy extension phase. 
3.6.5. Physical Examinations 
Complete physical examinations consist of assessments of general appearance; skin; head, 
eyes, ears, nose, and throat (HEENT); mouth, heart; lungs; abdomen; extremities; neurologic 
and auditory function; back; and lymph nodes. In addition, dermatological full body exam 


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must be performed by the investigator, sub-investigator or a qualified health professional per 
local guidelines. Dermatological examinations should also include visual inspection of the 
breasts and external genitalia. 
Targeted physical examinations should include skin, heart, lung, and abdomen, neurologic 
and auditory function, and examination of body systems where there are symptom 
complaints by the participant. 
Physical examinations will be performed at times specified in the schedule of activities in the 
protocol. 
In addition, at the times specified in the protocol, all patients will have an audiological 
evaluation including BAEP by an audiologist and a neurological evaluation by a specialist. 
4. ANALYSIS SETS 
For purposes of analysis, the following populations are defined: 
 
Analysis Set 
Description 
Safety Analysis Set (SAS) 
All participants taking at least 1 dose of study intervention. Participants 
will be analyzed according to the intervention they actually received. 
Efficacy Analysis Set (EAS) 
All randomized participants taking at least 1 dose of study intervention. 
Data will be summarized according to the intervention they were assigned. 
5. GENERAL METHODOLOGY AND CONVENTIONS 
The primary analysis for this study will be conducted following the primary completion date 
(PCD) at Month 9 and after the Month 9 data are cleaned and locked. 
5.1. Hypotheses and Decision Rules 
For the primary safety endpoint, there is no formal hypothesis testing. The analyses will 
focus on estimation. Summary statistics for each group with 95% confidence intervals will be 
provided. 
No estimands will be defined since there is no formal statistical hypothesis testing for this 
study. 
5.2. General Methods 
In the placebo-controlled period, the following continuous endpoints: (change from baseline 
in I-V interwave latency on BAEP, change from baseline in amplitude of wave V, and 
change from baseline in overall and AA SALT score, will be analyzed using the linear 
mixed -effects model with baseline, treatment group, visit, and treatment group by visit 
interaction as fixed effects, with an unstructured covariance matrix assumption, if there are 
convergence issues, a compound symmetry matrix will be used. The Kenward-Roger degrees 
of freedom approximation will be used. For participants who switch to the active therapy 
extension phase at Month 6, only their data through Month 6 will be included in the analysis 
of the placebo-controlled period. Descriptive statistics based on observed data will also be 
provided. For TP2 and TP3, descriptive statistics will be presented. 


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For the binary endpoint PGI-C response, in the placebo-controlled phase, number and 
percentage of responders with 95% confidence interval (based on Clopper-Pearson method) 
by treatment group, and treatment difference with 95% confidence intervals (based on Chan 
and Zhang’s exact method)4 will be presented. Participants who discontinue from the study 
for any reason or who switch to active therapy extension phase before Month 9 will be 
considered as non-responders. Number and percentage based on observed data will also be 
provided. For TP2 and TP3, number and percentage of responders with 95% confidence 
interval (based on Clopper–Pearson method) will be presented based on observed data. 
For all other data, descriptive summary statistics such as number and percentage will be 
presented for binary variables, and number, mean, standard deviation (or standard error of the 
mean), median, minimum, and maximum will be presented for continuous variables. 
5.3. Methods to Manage Missing Data 
 
For the PCD CSR 
• 
For change from baseline in I-V interwave latency on BAEP, change from baseline 
in amplitude of wave V, and change from baseline in overall and AA SALT score 
during the placebo-controlled phase, the missing values will be handled in a linear 
mixed-effects model (Section 5.2). 
• 
For the PGIC response, participants who discontinue from the study for any reason 
or who switch to active therapy extension phase before Month 9 will be considered 
as non-responders at Month 9. 
 
For supplemental CSR 1 and CSR 2 
• 
All efficacy data will be summarized based on observed data. Missing data will not 
be imputed. 
6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoint 
• Primary endpoint: Change from baseline in I-V interwave latency on BAEP at a 
stimulus intensity of 80 decibels (dB) at Month 9; 
• Population: Safety; 
• Statistical Method: a linear mixed-effects model in Section 5.2, which includes all the 
post-baseline measurements through Month 9, will be used. The estimated means, 
with standard errors and 95% confidence intervals for each treatment group based on 
the model will be presented. Descriptive statistics will also be provided based on the 
observed data. Data from right side and left side will be summarized separately. 


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6.2. Secondary Endpoints-Safety 
6.2.1. I-V Interwave Latency on BAEP 
• Endpoint: Change from baseline in I-V interwave latency on BAEP at a stimulus 
intensity of 80dB at Months 6, 9E, and 15E. 
• Population: Safety. 
• Statistical Method: Linear mixed-effects model in Section 5.2, which includes all the 
post-baseline measurements through Month 6, will be used. The estimated means, 
with standard errors and 95% confidence intervals for each treatment group based on 
the model will be presented. Descriptive statistics will also be provided based on the 
observed data. Descriptive statistics will be presented for data in the active therapy 
extension phase. Data from right side and left side will be summarized separately. 
6.2.2. Percentage of IENF with Axonal Swellings in Skin Punch Biopsies 
• Endpoint: Change from baseline in the percentage of IENF with axonal swellings in 
skin punch biopsies at Month 9/EOP (End of placebo-controlled phase/ beginning of 
active therapy extension phase) and Month 15E. 
• Population: Safety. 
• Statistical Method: Descriptive statistics for continuous variables. 
6.2.3. IENFD in Skin Punch Biopsies 
• Endpoint: Change from baseline in IENFD in skin punch biopsies at Month 9/EOP 
and Month 15E. 
• Population: Safety. 
• Statistical Method: Descriptive statistics for continuous variables. Descriptive 
Summary of absolute and change from baseline in IENFD normalized by age and 
gender will also be provided. 
• For each participant normalized IEFND data was obtained by dividing the 
IEFND by the value of the LLN of each age range and gender, and 
multiplying it by 100 to obtain percentages. LLN is given by the 5th percentile 
of the distribution of IENFD by gender and age: females in age ranges of 18- 
39, 40-59 and 60+ are 8.0, 5.4 and 3.5 respectively, and for males, 5.9, 4.6 and 
3.3 respectively. 
6.2.4. Amplitude of Wave V on BAEP 
• Endpoint: Change and percent change from baseline in amplitude of wave V on 
BAEP at a stimulus intensity of 80dB at Months 6, 9, 9E, and 15E. 
• Population: Safety. 


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• Statistical Method: For change from baseline, a linear mixed-effects model for 
Months 6 and 9 in Section 5.2 wil be used. The estimated means, with standard errors 
and 95% confidence intervals for each treatment group based on the model will be 
presented. Descriptive statistics based on observed data will also be provided. 
Descriptive statistics will be presented for data in the active therapy extension phase. 
Data from right side and left side will be summarized separately. For percent change 
from baseline, descriptive statistics will be presented. 
6.2.5. Absence of Wave V on BAEP 
• Summary: Proportion of subjects with an absence of wave V on BAEP at stimulus 
intensities ranging from 80dB to 40dB at Months 6, 9, 9E, and 15E. 
• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. Data from right side and left side will be summarized separately. 
6.2.6. Incidence of Treatment-emergent Adverse Events (TEAEs) 
• Endpoint: Incidence of subjects with treatment emergent adverse events. 
• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. 
6.2.7. Incidence of Treatment-emergent Serious Adverse Events (TESAEs) 
• Endpoint: Incidence of Treatment-emergent serious adverse events. 
• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. 
6.2.8. Incidence of Adverse Events (AEs) Leading to Discontinuation 
• Endpoint: Incidence of Adverse events (AEs) leading to discontinuation. 
• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. 
6.2.9. Incidence of Clinically Significant Abnormalities in ECG (only QTcF) and Vital 
Signs 
• Endpoint: Incidence of clinically significant abnormalities in ECG (only QTcF) and 
vital signs. 


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• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. 
6.2.10. Incidence of Clinically Significant Abnormalities in Clinical Laboratory Values 
• Endpoint: Incidence of clinically significant abnormalities in clinical laboratory 
values. 
• Population: Safety. 
• Statistical Method: Descriptive statistics with number and percentage of subjects with 
the events only. 
6.3. Secondary and exploratory Endpoints-Efficacy 
6.3.1. Overall and AA SALT Scores 
• Endpoint: Change from baseline in overall and AA SALT scores in all the timepoins 
collected. 
The AA SALT score at each visit will be calculated using non-AA SALT scores as 
follows: 
• the non-AA SALT score collected at Month 9 (or Month 6) or the Early 
Termination visit (as appropriate) will be used for visits in TP1. 
• the non-AA SALT score collected at Month 15E or the Early Termination 
visit (as appropriate) will be used for visits in TP2, and 
•  the non-AA SALT score collected at Month 51E or the Early Termination 
visit (as appropriate) will be used for visits in TP3. 
• The formula for deriving the AA SALT score is given by: AA SALT score = 
overall SALT score – non-AA SALT score. 
• non-AA scores that were blank will be considered as zero in cases there was 
no medical history indicating AGA 
• Population: Efficacy. 
• Statistical Method: For placebo-controlled phase, a linear mixed-effects model in 
Section 5.2 will be used. The estimated mean, standard errors and 95% confidence 
intervals for each treatment group, and mean difference with 95% confidence interval 
will be presented at each time point. Descriptive statistics will be presented for data in 
TP2 and TP3. 


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6.3.2. PGI-C Response 
• Summary: Proportion of subjects with PGI-C response defined as greatly improved or 
moderately improved at all the timepoints collected. 
• Population: Efficacy. 
• Statistical Method: For placebo-controlled phase, statistics including number and 
percentage with 95% confidence interval (based on Clopper-Pearson method) by 
treatment group, and treatment difference with 95% confidence interval (based on 
Chan and Zhang’s exact method) will be presented. Missing data will be treated as 
non-responders. Summary based on observed data will also be provided. For TP2 and 
TP3, descriptive statistics including number and percentage with 95% confidence 
interval (based on Clopper–Pearson method) will be presented based on observed 
data. 
6.4. Other Endpoints 
Not applicable. No pharmacokinetic or pharmacodynamic parameters were evaluated in this 
study. 
6.5. Subset Analyses 
No subgroup analyses will be performed. 
6.6. Baseline and Other Summaries and Analyses 
6.6.1. Baseline Summaries 
Demographics and medical history will be summarized for all participants. Baseline disease 
characteristics will also be summarized. 
6.6.2. Study Conduct and Subject Disposition 
Subjects evaluation, disposition, and discontinuation will be summarized for all participants. 
6.6.3. Study Treatment Exposure 
A summary of compliance and the number of doses received as well as the median total dose 
by visit and groups will be provided. Compliance (%) = (sum of actual number of doses / 
sum of planned number of doses) * 100 for each visit period. Where sum of actual number of 
doses = total duration of each visit period* actual dose (Tablet) and sum of planned number 
of doses = total duration of each visit period* planned dose (Tablet) 
Duration of treatment in months will be summarized by the total number of days of dosing, 
calculated by (last dosing end date - first dosing start date + 1 - number of missed or zero 
doses days)/ 30.4375.. 
For a specific dosing record, if the dosing end date is missing and the participant is still in the 
study, then the CSR cut-off date will be applied. 


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6.6.4. Concomitant Medications and Non-Drug Treatments 
Prior drug and non-drug treatments, concomitant drug and non-drug treatments will be 
summarized for all participants. 
6.6.5. Alopecia areata history 
Alopecia areata history will be summarized. 
• 
Participants with a SALT score of <100% at Baseline (regardless of the category in the 
AA history CRF) will be categorized as non-AT/non-AU. 
• 
Participants with a SALT score of 100% at Baseline (regardless of the category in the 
AA history CRF) will be categorized as AT/AU. 
• 
Within the AT/AU category, classification into the AT and AU subcategories will be 
based in the AA history CRF; 
• 
Participants with a SALT score of 100% at Baseline who were not classified as AT 
or AU in the AA history CRF are considered as "Not specified". 
6.7. Safety Summaries and Analyses 
Safety analysis will be based on the safety population. 
Analyses for the primary and secondary safety endpoints are discussed in Section 6.1 and 
Section 6.2. 
In general, 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 Standards. Categorical outcomes (eg, AEs) will be summarized by 
subject counts and percentage. Continuous outcome (eg, blood pressure, pulse rate, etc.) will 
be summarized using N, mean, median, standard deviation, etc. Change from baseline in 
laboratory data, ECGs and vital signs will also be summarized. Subject listings will be 
produced for these safety endpoints accordingly. Clinically significant abnormalities in vital 
signs and clinical laboratory values are discussed in Sections 6.2.9 and 6.2.10. 


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In order to report the impact of COVID-19 on clinical trial popuations and study data, 
additional listings and summaries will be produced: 
• 
Protocol deviations related to COVID-19 
• 
Summary of discontinuations due to COVID-19 related reasons 
• 
Discontinuation from study/study drug interruptions due to COVID-19 related adverse 
events 
• 
COVID-19 related adverse events 
• 
Number of days with missed doses due to COVID-19 
• 
Missed visits summary for I-V interval latency on BAEP 
6.7.1. Adverse Events 
The safety data will be summarized in accordance with CDISC and Pfizer Standards (CaPS). 
All safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, categorical summaries, and graphical presentations. 
Adjudication data will be reported separately. 
6.7.2. Laboratory Data 
Laboratory data will be listed and summarized in accordance with the Pfizer reporting 
standards. Summaries of subjects meeting pre-specified monitoring and discontinuation 
criteria will be created using methods for categorical data. 
6.7.3. Vital Signs 
Vital signs will be summarized at baseline and all-available post-baseline visits. 
Height will be collected pre-dose and weight will be collected at pre and post dose. 
6.7.4. Electrocardiogram 
ECG parameters QTcF and change from baseline will be summarized at baseline and all 
available post-baseline visits. Categorization of QTcF will also be provided. 


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7. INTERIM ANALYSES 
There is no formal interim analysis planned in this study. However, if required, interim 
analyses may be performed for study monitoring for internal decision making, due to 
regulatory requests, or to support regulatory submissions. As no statistical hypotheses will be 
tested in this study, there are no issues of protecting the Type I error rate. 
This study uses an External Data Monitoring Committee (E-DMC). The E-DMC will be 
responsible for ongoing monitoring of safety of subjects in the study according to the DMC 
charter. The recommendations made by DMC to alter the conduct of the study will be 
forwarded to the appropriate Pfizer personnel for final decision. Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of safety data, to regulatory 
authorities, as appropriate. 
Independent safety adjudication committees will be used for opportunistic infections, 
cardiovascular events, neurological, including audiological events, and malignancy events. 
8. TIMING AND TREATENT GROUPS DISPLAYED FOR EACH ANALYSIS 
There will be 3 Clinical Study Reports (CSRs) for this study: one PCD-CSR, and two 
supplemental CSRs. 
8.1. PCD-CSR 
The PCD-CSR will include the primary analysis for this study, which will be conducted 
following the PCD at Month 9 (TP1), and after the Month 9 data are cleaned and locked for 
all participants. The following data will be included: 
• 
Efficacy data through Month 9 (TP1) 
• 
All safety data collected through the PCD data cut-off date 
For duration of treatment, concomitant medication, lab abnormality, lab values meeting 
discontinuation criteria, vital signs/QTcF values meeting pre-specified criteria and AE 
tables, the following groups will be summarized: 
 
Table 3. 
Groups 
 
Period 
Groups 
Placebo-controlled phase (TP1) 
• Ritlecitinib 200/50 mg QD 
• Placebo 
Active therapy extension phase (TP2) 
• Ext Ritlecitinib 50 mg QD 
• Ext Ritlecitinib 200/50mg QD 
Overall (TP1+TP2) 
• Ritlecitinib 200/50/50 mg QD 
• Any Ritlecitinib 
• Any Ritlecitinib + Placebo (Total) 


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For tables summarizing data by visit (such as BAEP, skin punch biopsy endpoints and 
efficacy endpoints), which only include data from TP1 in the PCD-CSR, the following 
groups will be summarized: 
• Ritlecitinib 200/50 mg QD 
• Placebo 
For other tables such as dispositions, demographic and baseline characteristics, medical 
history, primary diagnosis, prior medications and compliance the groups to be summarized 
will be: 
• Ritlecitinib 200/50 mg QD 
• Placebo → Ritlecitinib 200/50 mg QD. 
8.2. Supplemental CSR 1 
The supplemental CSR 1 will be prepared after the last participant completes the 4-week 
follow-up visit, or the Month 15E visit (TP2) if the last participant is enrolled in TP3, 
whichever is later. This CSR will include: 
• 
Efficacy through Month 15E (TP1+TP2). Efficacy data from participants while they are 
on the Observation Period will not be included in the summaries of efficacy. Instead, 
listings and plots may be provided. 
• 
All safety data collected through the cut-off date for this CSR (including the Follow-up 
Period and the Observation Period). 
For summaries in this CSR, the groups will be the following: 
• 
For duration of treatment, concomitant medication, lab abnormality, lab values meeting 
discontinuation criteria, vital signs/QTcF values meeting pre-specified criteria and AE 
tables. 
 
Table 4.  Groups 
 
Period 
Groups 
Placebo-controlled phase (TP1) 
• Ritlecitinib 200/50 mg QD 
• Placebo 
Active therapy extension phase (TP2) 
• Ext Ritlecitinib 50 mg QD 
• Ext Ritlecitinib 200/50mg QD 
Overall (TP1+TP2+TP3+Observation 
period) 
• Ritlecitinib 200/50/50 mg QD 
• Any Ritlecitinib 
• Any Ritlecitinib + Placebo (Total) 


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• 
For all the other tables, groups will be: 
o 
Ritlecitinib 200/50/50 mg QD 
o 
Placebo → Ritlecitinib 200/50 mg QD. 
8.3. Supplemental CSR 2 
The supplemental CSR 2 will be focused on safety and efficacy data from TP3 and will be 
prepared after the last participant completes the last visit or discontinues from the study. 
• Disposition date of TP2 (or of 4 weeks follow-up period if participants didn’t enter 
TP3) will be used to identify records in TP2 and TP3. 
• All safety data in TP3, regardless of whether participants are in the Observation 
Period or not, will be included in summary tables. 
• Only one group “All participants” including all participants will be used in all 
summaries. 
• Efficacy data of participants while in the Observation Period will not be included in 
summary tables that present TP3 data by visit. Instead, listings and plots may be 
provided. 
9. ENDPOINTS INCLUDED IN EACH CSR 
Efficacy analysis 
 
PCD CSR (Month 9; TP1) 
Endpoint 
Endpoints 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
PGI-C response 
• 
Overall and AA SALT. 
Exploratory 
• There are no exploratory efficacy endpoints included in this CSR 
Supplementary CSR 1 (Month 15E; TP2) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
PGI-C response 
• 
Overall and AA SALT 
Exploratory 
• 
There are no exploratory efficacy endpoints included in this CSR. 


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Supplementary CSR 2 (Month 51E; TP3) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary efficacy endpoints. 
Secondary 
• 
There are no secondary efficacy endpoints included in this CSR. 
Exploratory 
• 
PGI-C response 
• 
Overall and AA SALT score 
 
Safety 
 
PCD CSR (Month 9; TP1) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
Change from baseline in I-V interwave latency on BAEP at Month 9 
Secondary 
• 
Change from baseline in I-V interwave latency on BAEP at Month 6 
• 
Change from baseline in IENFD at Month 9 
• 
Change from baseline in percentage of IENF with axonal swellings in skin punch 
biopsies at Month 9 
• 
Change and percent change from baseline in amplitude of wave V at Months 6 and 9 
• 
Absence of wave V on BAEP at Months 6 and 9 
• 
The incidence rates of safety events, significant clinical abnormalities, vital signs and 
ECG 
Supplementary CSR 1 (Month 15E; TP2) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary safety endpoints included in the supplemental CSR 1. 
Secondary 
• 
Change from baseline in I-V interwave latency on BAEP 
• 
Change from baseline in IENFD 
• 
Change from baseline in percentage of IENF with axonal swellings from skin punch 
biopsies 
• 
Change and percent change from baseline in amplitude of wave V 
• 
Absence of wave V on BAEP 
• 
The incidence rates of safety events, significant clinical abnormalities, vital signs and 
ECG 
 
Supplementary CSR 2 (Month 51E; TP3) 
Endpoint 
Statistical Analysis Methods 
Primary 
• 
There are no primary safety endpoints included in the supplemental CSR 2. 
Secondary 
• 
Incidence rates of safety events, significant clinical abnormalities and vital signs 


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10. REFERENCES 
1. 
Waliszewska-Prosól, M, et al. Visual and brainstem auditory evoked potentials in 
HCV-infected patients before and after interferon-free therapy — A pilot study. 
International Journal of Infectious Diseases 80 (2019) 122–128. 
2. 
Mohamed, E, et al. Auditory system dysfunction in patients with vitiligo: is it a part of 
a systemic autoimmune process? The Egyptian Journal of Otolaryngology. 2017, 
33:594–602. 
3. 
Baweja, P, et al. Changes in brainstem auditory evoked potentials among North Indian 
females with Type 2 diabetes mellitus. Indian Journal of Endocrinology and 
Metabolism / Nov-Dec 2013 / Vol 17 | Issue 6. 
4. 
Chan, IS, Zhang, Z. Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics. 1999;55(4):1202-9. 


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11. APPENDICES 
11.1. Appendix 1 Definition and Use of Visit Windows in Reporting 
Visit windows will be used for efficacy variables and for any safety data that are displayed or 
summarized by study visit. 
 
Visit Label 
Target Day 
Analysis Visit Window 
Baseline 
1 
Up to Day 1 
Month 1 
31 
Days 2 to 60 
Month 3 
91 
Days 61 to 136 
Month 6 
181 
Days 137 to 226 but <=Day 1E 
Month 9 
271 
Days 227 to 316 but <=Day 1E 
Month 3E 
91E 
Days 2E to 136E 
Month 6E 
181E 
Days 137E to 226E 
Month 9E 
271E 
Days 227E to 316E 
Month 12E 
361E 
Days 317E to 406E 
Month 15E 
451E 
Day 407E to 541E 
Month 21E 
631E 
Day 542E to 721E 
Month 27E 
811E 
Day 722E to 901E 
Month 33E 
991E 
Day 902E to 1081E 
Month 39E 
1171E 
Day 1082E to 1261E 
Month 45E 
1351E 
Day 1262E to 1441E 
Month 51E 
1531E 
Day 1442 to last dose + 14 days 
28-Day Follow-up 
28 days after last dose 
Based on nominal visit 
6-Month Follow-up 
182 days after 
discontinuation 
Based on nominal visit 
E=relative day to the first dose at active therapy extension phase. 
 
If more than one observation falls within a visit window, the observation that is the closest to 
the target date for that visit will be used for the summary tables. If two visits are equally 
distant from the target day, the data from the later visit will be used. 
Data collected in TP2, from the first dose in TP2 till the end of follow-up or the first dose in 
TP3, will be used to derive analysis visits in TP2. Data collected in TP3, from the first dose 
in TP3 or the Observation Period will be used to derive analysis visits in TP3. 
Some endpoints (eg, BAEP) are not scheduled to be assessed at each visit and some 
measurement may fall outside the scheduled visit windows. In this case, for variables where 
mixed model methodology is used, the data from the unscheduled ‘windowed’ visits will not 
be included in mixed model analysis. However, these visits will be summarized descriptively 
in the observed cases analysis, using the visit timepoint corresponding to their actual visit 
window (for example a participant with a visit on Day 59 will be summarized at Month 1 in 
the observed case summaries). 


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11.2. Appendix 2 List of Countries by Region 
 
Region 
Countries 
North America 
Canada, United States 
Europe 
Poland 
Rest of World 
Australia, Argentina, Chile, Colombia, Mexico 


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11.3. Appendix 3 Study Days Used to Define Each Visit Period in the Calculation of By 
Visit Table for Compliance. 
Month 1: Day 1 – Day 31 
Month 3: Day 32 to Day 91 
Month 6: Day 92 to Day 181 
Month 9: Day 182 to Day 1E -1 
Month 3E: Day 1E to Day 91E 
Month 6E: Day 92E to Day 181E 
Month 9E: Day 182E to Day 271E 
Month 12E: Day 272E to Day 361E 
Month 15E: Day 362E to Day 451E 
Month 21E: Day 452E to Day 631E 
Month 27E: Day 632E to Day 811E 
Month 33E: Day 812E to Day 991E 
Month 39E: Day 992E to Day 1171E 
Month 45E: Day 1172E to Day 1351E 
Month 51E: Day 1352E to Day 1531E