Conditions: Atopic Dermatitis
Keywords: atopic dermatitis atopic eczema eczema JAK janus kinase
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 46
Healthy volunteers: no

Brief summary:
B7451037 is a randomized, double-blind, placebo-controlled, parallel-group, Phase 2a study to investigate the mechanism of action of PF-04965842 by correlating efficacy outcomes with changes from baseline in key skin and blood biomarkers in adult participants at least 18 years of age with moderate-to-severe atopic dermatitis. Participants will be screened within 28 days prior to the first dose of study intervention to confirm eligibility. A total of approximately 51 participants will be randomized in a 1:1:1 ratio to receive PF-04965842 200 mg once daily (QD), PF004965842 100 mg QD, or matching placebo QD for 12 weeks. At the end of the 12-week study treatment, qualified participants will have the option to enter the long-term extension study B7451015 (NCT03422822). Participants discontinuing early from this study will undergo a 4-week off-treatment follow-up period.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None

Interventions: intervention 1: PF-04965842 200 mg intervention 2: PF-04965842 100 mg intervention 3: Placebo
Intervention descriptions: intervention 1: PF-04965842 200 mg administered as two tablets to be taken orally once daily for 12 weeks intervention 2: PF-04965842 100 mg administered as two tablets to be taken orally once daily for 12 weeks intervention 3: Placebo administered as two tablets to be taken orally once daily for 12 weeks

Protocol document:
Prot_004.pdf: 
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TITLE PAGE
Protocol Title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO INVESTIGATE 
THE MECHANISM OF ACTION OF ABROCITINIB MONOTHERAPY IN ADULT 
PARTICIPANTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
Protocol Number: B7451037
Amendment Number: 3
Compound Number: PF-04965842
Study Phase: Phase 2a
Short Title: Study evaluating the mechanism of action of abrocitinib monotherapy for 
participants with moderate-to-severe atopic dermatitis 
Acronym: JADE MOA
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
123554
EudraCT
Not Applicable
Approval Date: 12 November 2020
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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Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Amendment 3
11 Nov 2020
Amendment 2
10-Dec-2019
Amendment 1
05-Sep-2019
Original Protocol
22-Feb-2019
Amendment 3 (30-Oct-2020)
Overall Rationale for the Amendment 3:
Section # and 
Name
Description of Change
Brief Rationale
Exclusion 
criteria#4
Added the following text:

Have increased risk of 
developing venous 
thromboembolism, e.g. deep 
vein thrombosis or 
pulmonary embolism:
o
History of venous 
thromboembolism, 
or 
o
First-degree relative 
with unprovoked 
venous 
thromboembolism 
(i.e. without known 
underlying cause 
such as trauma, 
surgery, 
immobilization, 
prolonged travel, 
pregnancy, hormone 
use, or plaster cast), 
that would suggest 
participant is at 
increased risk of 
inherited 
Per updated safety information, participants 
with increased risk of developing venous 
thromboembolism are excluded.


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Section # and 
Name
Description of Change
Brief Rationale
coagulation disorder 
(e.g. Factor V 
Leiden).
Exclusion criteria 
#2 and 8.2.9
8.2.9. Suicidal 
Ideation 
(Columbia 
Suicide Severity 
Rating Scale)
The participant must have a risk 
assessment done by a qualified Mental 
Health Professional (MHP) to assess 
whether it is safe to participate in the 
trial if the participant’s responses on 
any of the screening instruments or 
other screening information indicate
Participants who have recurrent SIB 
during the trial must be discontinued 
from the study and treated 
appropriately. If a participant endorses 
a 4 or 5 on the ideation subscale or 
any behavioral item of the C-SSRS on 
2 occasions and is confirmed to have 
active SIB on both occasions by a risk 
assessment conducted by a qualified 
MHP, then the participant must be 
discontinued from the study and 
treated appropriately.
Language changed from “should” to “must” 
and changed from “on more than 2 occasions” 
to “on 2 occasions”
Language changed from “should” to “must” 
and changed from “on more than 2 occasions” 
to “on 2 occasions”
9.1. Estimands 
and Statistical 
Hypotheses
Text added: Participants need to have 
a baseline and week 12 assessment to 
be included in the analysis.
Added clarification to estimands and statistical 
hypotheses
9.5 Interim 
analysis
Text removed: There are no formal 
interim analyses planned. There will 
be a program-level EDMC (see 
below) who will periodically review 
the safety data from the study.
Text added: After the first 15 
participants have completed the study, 
there will be an interim analysis to 
examine platelet values. A 
longitudinal analysis will be 
conducted to determine if there is a 
change from baseline in platelet 
values. The data will remain blinded 
so that no one will know the 
participants’ assigned treatment and 
thus the analysis will not analyse for 
any treatment differences. Correlation 
analyses may also be conducted to 
look for potential relationships 
Added interim analysis


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Section # and 
Name
Description of Change
Brief Rationale
between platelet values and other 
laboratory measures, such as TPO. 
There will not be any decision rules 
associated with this interim analysis, 
so there will be no changes to the 
conduct or continuation of the trial 
based on these analyses.
10.1.5
Added hepatic
Hepatic committee has been added on a 
program level
 
 
 
 
 
 
 
 
 
Appendix 13. 
Alternative 
Measures During 
Public 
Emergencies 
Appendix
Added Alternative Measures During 
Public Emergencies Appendix
Language and an appendix were added to 
address COVID-19 and to describe alternative 
measures to be taken during public 
emergencies.
Sections 7.2, 8.3, 
and 10.3
Language from new protocol template 
has been incorporated.
Language updated per new protocol template.
Appendices 12, 
13, 14, 15, 16
have been 
removed
Appendices have been removed to 
avoid any copyright issues when the 
protocol is publicly disclosed and in 
case any changes are made to the 
approved version.
Appendices removed per SciOPs 
recommendations.
Amendment 2 (10-Dec-2019)
Overall Rationale for the Amendment:
Section # and 
Name
Description of Change
Brief Rationale
1.1. Synopsis
 
 
 
 
 
 
1.3. Schedule of 
Activities
Addition of hematology assessment at 
Day 4.
Added timepoint considered important in 
understand time course of any changes. 
1.3. Schedule of 
Activities
Blood collection for biomarker 
evaluation – updated to differentiate 
sample types and timepoints. 
Amended for clarity.
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Section # and 
Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities
 
 
 
 
1.3. Schedule of 
Activities
 
 
2.0 Introduction -
Abrocitinib
Involvement in 
Hematopoiesis
Text amended and ‘Both platelets and 
RBC derive from the same progenitor. 
Hence, changes in one compartment 
can affect the other.’ added. 
Amended for clarity.
3. Objectives, 
Estimands and 
Endpoints
 
 
 
 
 
 
4.1 Overall 
Design
 
 
 
 
4.1 Overall 
Design
 
 
 
 
 
 
 
8.1.6 
Investigator’s 
Global 
Assessment 
(IGA)
IGA amended to no longer exclude 
scalp, palms, and soles from the 
assessment/scoring.
To be consistent with other protocols in 
program.
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Section # and 
Name
Description of Change
Brief Rationale
8.1.7 Eczema 
Area and 
Severity Index 
(EASI) 
EASI amended to no longer exclude 
scalp, palms, and soles from the 
assessment/scoring.
To be consistent with other protocols in 
program.
8.1.7.1 Body 
Surface Area 
Efficacy
Assessment amended to include scalp, 
palms, and soles.
To be consistent with other protocols in 
program.
8.1.8 
Hematopoiesis 
evaluation
Text amended and moved in part to 
section 8.8.
Amended for clarity.
 
 
 
 
 
 
 
 
 
 
8.5 
Pharmacokinetics
Sample volume amended from 
‘minimum 3.2 mL’ to approximately 4 
mL
To be consistent with other protocols in 
program.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.8.2 Specified 
protein research
Section removed – details provided in 
section 8.8.
Removes duplication.
8.8.3 Specified 
gene expression 
research
Section removed – details provided in 
section 8.8.
Removes duplication.
 
 
 
 
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Amendment 1 (05-Sep-2019)
Overall Rationale for the Amendment:
Section # and 
Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities
Columbia Suicide Severity Rating 
Scale (C-SSRS) assessments added to 
screening, baseline, Week 8, Week 12, 
and Week 16 visits.
Columbia-Suicide Severity Rating Scale (C-
SSRS) has been added to on-study visits as a 
monitoring instrument for SIB for all 
participants in recognition of the heightened 
background risk of SIB in the patient 
population. Patients with medically significant 
SIB concerns identified during the study will 
be referred for an evaluation by a mental health 
professional to determine the appropriateness 
of continuing in the study.
1.3. Schedule of 
Activities
Addition of Patient Health 
Questionnaire – 8 Items (PHQ-8) to be 
administered at screening.
Patient Health Questionnaire – 8 Items will be 
administered at screening to assess 
participants’ depression level.
1.3. Schedule of 
Activities
 
 
 
 
 
2.2.3. Summary 
of abrocitinib 
Clinical 
Pharmacokinetics
Addition of the following text:
Plasma profiling from the [14C] 
abrocitinib human mass balance study 
(B7451008) indicated parent as the 
most prevalent circulating species 
(26%), with 3 major and more polar 
mono-hydroxylated metabolites 
identified: PF-06471658 (3-
hydroxypropyl, 11%), PF-07055087 
(2-hydroxypropyl, 12%), and PF-
07054874 (pyrrolidinone pyrimidine, 
14%).
Background section has been updated by 
adding description of mass balance Study 
B7451008 findings.
3. Objectives, 
Estimands, and 
Endpoints
 
 
 
 
 
 
4. Study Design
 
 
 
5.1. Inclusion 
Criteria
Clarification that documentation of 
inadequate response to topical therapy 
for AD must include 4 consecutive
weeks of treatment.
Clarification that documentation of inadequate 
response to topical therapy for AD must 
include 4 consecutive weeks of treatment.
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Section # and 
Name
Description of Change
Brief Rationale
5.2. Exclusion 
Criteria
Updated exclusion criteria on suicidal 
ideation. Removed text on active 
suicidal ideation from Exclusion 
Criterion 1 and updated Exclusion 
Criterion 2 to include risk assessment 
done by a qualified Medical Health 
Professional (MPH) to assess whether 
it is safe for the subject to participate 
in the trial. Addition of criteria for 
PHQ-8 assessment of clinically 
significant depression. 
Exclusion criteria have been broadened, 
removing the exclusion of patients with 
suicidal ideation and behavior (SIB), to ensure 
patients with more severe AD are considered 
eligible for the study, thus improving the 
generalizability of the study. Patients with 
medically significant SIB concerns identified 
during screening will be referred for an 
evaluation by a mental health professional to 
determine the appropriateness of participation 
in the study.
5.2. Exclusion 
Criteria
Deleted text on details of Hepatitis B 
and Hepatitis C testing in Exclusion 
Criterion 7 and moved to Appendix 2.
Criterion was updated for greater clarity –
details of reflex testing moved to Appendix 2.
5.2. Exclusion 
Criteria
Updated Exclusion Criterion 19 to 
change marked prolongation of QTcF 
interval from >450 to >500 
milliseconds on the screening ECG 
and to delete text on history of 
additional risk factors for Torsade de 
Pointes and use of concomitant 
medications that prolong the 
QT/QTcF interval.
Criterion was updated based on results of 
thorough QT study.
5.4. Screen 
Failures
Added the following text:
Individuals for whom screen failure is 
related to failing the disease severity 
(including extent of disease) inclusion 
criterion and who subsequently 
experience worsening AD, which in 
the investigator’s judgement would 
make them eligible for participation, 
may be considered for re-screening. 
Such cases should be discussed with 
the Pfizer Medical Monitor (or 
designee) to determine if re-screening 
is appropriate.
Section was updated to clarify circumstances 
under which rescreening may be permitted.
6.5.2. Prohibited 
Medications and 
Treatments
Addition that excluded prior treatment 
with systemic JAK inhibitors and 
deleted parenthetical text of oral or 
topical.
Section was updated for consistency with 
eligibility criteria.
8.1.1. Rater 
Qualifications
Updated text to specify that clinical 
evaluations of atopic dermatitis (AD) 
should be performed by medical 
professional with experience in the 
conduct of dermatology clinical trials 
(not necessarily AD clinical trials) 
when designated by the primary site 
investigator.
Section was updated to allow less restrictive 
requirements for raters.


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Section # and 
Name
Description of Change
Brief Rationale
8.1.9.1. Peak 
Pruritus 
Numerical 
Rating Scale 
(NRS)
Added the following text:
The Peak Pruritus NRS as it is 
assessed on the day of the baseline 
visit will be included in the evaluation 
of Inclusion Criterion 2.
Section was updated for greater clarity.
8.2.8.1. Hepatitis 
Testing
Added text on the interpretation of 
Hepatitis B and Hepatitis C testing 
results for clarity.
Section was updated for greater clarity.
8.2.9. Suicidal 
Ideation
Updated text on administering and 
evaluation of C-SSRS and PHQ-8.
Added text indicates that participants 
should have a risk assessment done by 
a qualified MHP to assess whether it 
is safe to participate in the trial if the 
participant's responses on any of the 
screening instruments or other 
screening information indicate this 
based on criteria provided.
Columbia-Suicide Severity Rating Scale (C-
SSRS) has been added to on-study visits as a 
monitoring instrument for SIB for all 
participants in recognition of the heightened 
background risk of SIB in the patient 
population. Patients with medically significant 
SIB concerns identified during the study will 
be referred for an evaluation by a mental health 
professional to determine the appropriateness 
of continuing in the study.
8.2.9.1. 
Columbia 
Suicide Severity 
Rating Scale
Updated text on use of C-SSRS in SIB 
risk monitoring.
Section was updated to describe on-study 
monitoring of SIB risk factors
8.2.9.2. Patient 
Health 
Questionnaire - 8 
Items (PHQ-8)
Addition of section to describe the 
administration of PHQ-8 to assess the 
subject’s depression level.
Section was updated to describe on-study 
monitoring of SIB risk factors
8.5. 
Pharmacokinetics
Updated text to change blood sample 
volumes from 8 mL to 3.2 mL, and 
additional text to include measurement 
of abrocitinib metabolites 
PF-06471658, PF-07055087, and 
PF-07054874.
Updated text to reflect analysis of abrocitinib 
metabolites.
8.8.2. Banked 
Biospecimens for 
Biomarkers
Change blood volume for Prep B2.5 
from two 9 mL blood samples to 
one 4 mL blood sample.
Section was updated to correct the blood 
volume for Prep B2.5.
10.2. Appendix 
2: Clinical 
Laboratory Tests
Removed routine analysis of specific 
gravity for consistency with 
abrocitinib program.
Section was updated for consistency with 
abrocitinib program.
10.2. Appendix 
2: Clinical 
Laboratory Tests
Added HBV DNA testing for all 
countries; removed details that are 
explained elsewhere (redundancies).
Section was updated to clarify that HBV DNA 
reflex testing should be done regardless of 
geographic location.
10.10. Appendix 
10: Monitoring 
and 
Discontinuation 
Criteria
Updated text that serious infection 
“must result in temporary interruption 
of study intervention. Study 
intervention cannot be restarted until 
the serious infection has resolved, and 
Section was updated to provide investigators 
with greater clarity on how to handle potential 
discontinuations related to serious infection.


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Section # and 
Name
Description of Change
Brief Rationale
unless restarting study intervention 
has been discussed and agreed with 
the Pfizer medical monitor. If the 
participant cannot be restarted on 
study intervention within 21 days, or 
the infection is not resolved, or there 
is no agreement received from the 
Pfizer medical monitor to restart study 
intervention then the participant must 
be permanently discontinued from 
study intervention”.
Throughout
Minor typographical changes have 
been made throughout.
Typographical changes include biomarker 
names, eligibility criteria, cross-references, PK 
schedule and storage, and analysis set 
description.


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................16
LIST OF FIGURES .................................................................................................................16
1. PROTOCOL SUMMARY...................................................................................................17
1.1. Synopsis ..................................................................................................................17
1.2. Schema ....................................................................................................................22
1.3. Schedule of Activities (SoA)...................................................................................23
2. INTRODUCTION ...............................................................................................................33
2.1. Study Rationale .......................................................................................................34
2.2. Background .............................................................................................................35
2.2.1. Non-Clinical and Phase 1 Data...................................................................36
2.2.2. Phase 2b in AD (B7451006).......................................................................36
2.2.3. Summary of Abrocitinib Clinical Pharmacokinetics..................................37
2.2.4. Population Pharmacokinetics......................................................................38
2.3. Benefit/Risk Assessment.........................................................................................38
3. OBJECTIVES, ESTIMANDS AND ENDPOINTS ............................................................39
4. STUDY DESIGN.................................................................................................................43
4.1. Overall Design.........................................................................................................43
4.2. Scientific Rationale for Study Design.....................................................................45
4.3. Justification for Dose ..............................................................................................45
4.4. End of Study Definition ..........................................................................................46
5. STUDY POPULATION......................................................................................................47
5.1. Inclusion Criteria.....................................................................................................47
5.2. Exclusion Criteria....................................................................................................49
5.3. Lifestyle Considerations..........................................................................................55
5.3.1. Meals and Dietary Restrictions...................................................................55
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................55
5.3.3. Surgery........................................................................................................55
5.4. Screen Failures ........................................................................................................56
6. STUDY INTERVENTION..................................................................................................56
6.1. Study Intervention(s) Administered........................................................................56
6.2. Preparation/Handling/Storage/Accountability ........................................................57


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6.3. Measures to Minimize Bias: Randomization and Blinding.....................................57
6.4. Study Intervention Compliance...............................................................................58
6.5. Concomitant Therapy..............................................................................................59
6.5.1. Permitted Concomitant Treatments............................................................60
6.5.2. Prohibited Medications and Treatments .....................................................61
6.6. Dose Modification...................................................................................................61
6.7. Intervention after the End of the Study...................................................................61
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................62
7.1. Discontinuation of Study Intervention ....................................................................62
7.1.1. Temporary Discontinuation........................................................................62
7.2. Participant Discontinuation/Withdrawal from the Study........................................62
7.2.1. Withdrawal of Consent...............................................................................63
7.3. Lost to Follow up ....................................................................................................63
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................64
8.1. Efficacy Assessments..............................................................................................65
8.1.1. Rater Qualifications....................................................................................65
8.1.2. Skin Biopsies ..............................................................................................65
8.1.5. Photography of Representative AD Lesions...............................................66
8.1.6. Investigator’s Global Assessment (IGA)....................................................67
8.1.7. Eczema Area and Severity Index (EASI) ...................................................67
8.1.7.1. Body Surface Area – Efficacy (BSA Efficacy).........................70
8.1.9. Patient-reported Outcomes (PROs) ............................................................70
8.1.9.1. Peak Pruritus Numerical Rating Scale (NRS)...........................70
8.1.9.2. Night Time Itch Scale ...............................................................71
8.2. Safety Assessments .................................................................................................71
8.2.1. Physical Examinations and Medical History..............................................71
8.2.2. Vital Signs ..................................................................................................72
8.2.3. Chest X-Ray................................................................................................72
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8.2.4. Tuberculosis Testing...................................................................................73
8.2.5. Special Safety Assessment .........................................................................73
8.2.6. Skin Type Assessment................................................................................73
8.2.7. Electrocardiograms.....................................................................................74
8.2.8. Clinical Safety Laboratory Assessments ....................................................74
8.2.8.1. Hepatitis Testing .......................................................................75
8.2.8.2. Viral Studies..............................................................................75
8.2.9. Suicidal Ideation (Columbia Suicide Severity Rating Scale).....................75
8.2.9.1. Columbia Suicide Severity Rating Scale ..................................76
8.2.9.2. Patient Health Questionnaire – 8 Items (PHQ-8)......................76
8.2.10. Pregnancy Testing ....................................................................................77
8.3. Adverse Events and Serious Adverse Events..........................................................77
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......77
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................78
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF .................78
8.3.2. Method of Detecting AEs and SAEs ..........................................................78
8.3.3. Follow-up of AEs and SAEs.......................................................................79
8.3.4. Regulatory Reporting Requirements for SAEs...........................................79
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................79
8.3.5.1. Exposure During Pregnancy......................................................80
8.3.5.2. Exposure During Breastfeeding ................................................81
8.3.5.3. Occupational Exposure .............................................................81
8.3.6. Cardiovascular and Death Events...............................................................82
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................82
8.3.8. Adverse Events of Special Interest.............................................................82
8.3.8.1. Lack of Efficacy........................................................................82
8.3.9. Medical Device Deficiencies......................................................................82
8.3.10. Medication Errors.....................................................................................82
8.4. Treatment of Overdose............................................................................................83
8.5. Pharmacokinetics ....................................................................................................83
8.5.1. Shipment of Pharmacokinetic Samples ......................................................84


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8.7. Genetics...................................................................................................................85
8.7.1. Specified Genetics ......................................................................................85
8.7.2. Banked Biospecimens for Genetics............................................................85
8.8. Biomarkers ..............................................................................................................85
8.8.1. Specified Gene Expression Ribonucleic Acid (RNA) Research ................86
8.8.2. Banked Biospecimens for Biomarkers .......................................................86
8.9. Health Economics OR Medical Resource Utilization and Health Economics........87
9. STATISTICAL CONSIDERATIONS ................................................................................88
9.1. Estimands and Statistical Hypotheses.....................................................................88
9.1.1. Estimands....................................................................................................88
9.2. Sample Size Determination.....................................................................................88
9.3. Populations for Analyses.........................................................................................89
9.4. Statistical Analyses .................................................................................................89
9.4.1. Analysis of the Primary Endpoint...............................................................89
9.4.2.1. Analysis of Other Endpoints .....................................................92
9.4.3. Safety Analyses ..........................................................................................92
9.5. Interim Analyses .....................................................................................................93
9.5.1. Data Monitoring Committee (DMC)..........................................................93
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................94
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............94
10.1.1. Regulatory and Ethical Considerations ....................................................94
10.1.2. Financial Disclosure .................................................................................94
10.1.3. Informed Consent Process ........................................................................95
10.1.4. Data Protection .........................................................................................96
10.1.5. Committees Structure ...............................................................................96
10.1.6. Dissemination of Clinical Study Data ......................................................97
10.1.7. Data Quality Assurance ............................................................................98
10.1.8. Source Documents....................................................................................99
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10.1.9. Study and Site Closure..............................................................................99
10.1.10. Publication Policy.................................................................................100
10.1.11. Sponsor’s Qualified Medical Personnel ...............................................101
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................102
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................105
10.3.1. Definition of AE .....................................................................................105
10.3.2. Definition of SAE...................................................................................106
10.3.3. Recording/Reporting and Follow-Up of AE and/or SAE.......................107
10.3.4. Reporting of SAEs..................................................................................110
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..............................................................................................................112
10.5. Appendix 5: Genetics..........................................................................................115
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......116
10.7. Appendix 7: Prohibited Concomitant Medications.............................................118
10.8. Appendix 8: Country-specific Requirements......................................................119
10.9. Appendix 9: Abbreviations .................................................................................120
10.10. Appendix 10: Monitoring and Discontinuation Criteria ...................................125
10.11. Appendix 11: Diagnostic Criteria for Atopic Dermatitis..................................128
10.12. Appendix 12: Fitzpatrick Skin Type .................................................................129
10.13. Appendix 13: Alternative Measures During Public Emergencies.....................130
10.13.1. Telehealth Visits...................................................................................130
10.13.2. Alternative Facilities for Safety Assessments ......................................130
10.13.2.1. Laboratory Testing ..............................................................130
10.13.3. Study Intervention ................................................................................131
10.13.4. Home Health Visits...............................................................................131
10.13.5. Adverse Events and Serious Adverse Events.......................................132
10.13.6. Efficacy Assessments ...........................................................................132
10.13.7. Independent Oversight Committees .....................................................132
11. REFERENCES ................................................................................................................133


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LIST OF TABLES
Table 2.
Investigator’s Global Assessment (IGA) Score....................................................67
Table 3.
Clinical Sign Severity Scoring Criteria for the Eczema Area and Severity 
Index (EASI).........................................................................................................68
Table 4.
Handprint Determination of Body Surface Area (BSA).......................................69
Table 5.
Eczema Area and Severity Index (EASI) Area Score Criteria.............................69
Table 6.
Eczema Area and Severity Index (EASI) Body Region Weighting.....................69
Table 7.
Protocol-Required Safety Laboratory Assessments ...........................................103
LIST OF FIGURES
Figure 1.
Mean (90% CI) Percent Change from Baseline Versus Time for Platelets..........46
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1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO INVESTIGATE 
THE MECHANISM OF ACTION OF ABROCITINIB MONOTHERAPY IN ADULT 
PARTICIPANTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
Short Title: Study evaluating the mechanism of action of abrocitinib monotherapy for 
participants with moderate-to-severe atopic dermatitis 
Rationale:
Abrocitinib is a Janus kinase 1 (JAK1) inhibitor and is being developed as an oral treatment 
for participants with moderate-to-severe atopic dermatitis (AD).
Objectives, Estimands and Endpoints
Primary Objective
Primary Endpoint

To assess the effects of abrocitinib 
on lesional and non-lesional skin 
biomarkers of adult participants with 
moderate-to-severe AD.

Changes from baseline in AD 
biomarkers in skin, including 
biomarkers for general inflammation 
(MMP12), hyperplasia (K16), Th2 
immune response (CCL17, CCL18, 
CCL26), and Th22 immune 
response (S100A8, S100A9, 
S100A12).
Secondary Objectives
Secondary Endpoints

To evaluate the effect of abrocitinib 
on gene expression (evaluated by 
mRNA PCR and/or gene arrays).

Changes from baseline in gene 
expression (evaluated by mRNA 
PCR and/or gene arrays) over time 
in skin lesions.

To evaluate the effect of abrocitinib 
on inflammatory infiltrates (T-cell 
and dendritic cells) using 
immunohistochemistry (IHC) in skin 
biopsies.

Changes from baseline in cellular 
(T-cells and dendritic cells) markers 
using IHC in skin biopsies at various 
time points.

To evaluate the effect of abrocitinib 
on epidermal hyperplasia using IHC 
and RT-PCR in skin biopsies.

Changes from baseline in 
hyperplasia markers (thickness, 
K16, Ki67) in skin biopsies.

To assess the effect of abrocitinib on 
blood biomarkers (OLINK 
proteomic in serum).

Changes from baseline in blood 
biomarkers (OLINK proteomic 


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microassay for inflammation and 
immune response in serum).

To assess changes in T-cell 
lymphocyte subset populations in 
blood using flow cytometry.

Changes from baseline in T-cell 
lymphocyte subset populations in 
blood using flow cytometry.

To evaluate the effect of abrocitinib 
on pruritus and its correlation to 
IHC and genetic markers in lesional 
skin.

Response based on at least 4 points 
improvement in the severity of Peak 
Pruritus numerical rating scale 
(NRS) from baseline and change 
from baseline in IHC and genetic 
markers in lesional skin.
Efficacy Objective
Efficacy Endpoints

To evaluate the effect of abrocitinib 
on clinical efficacy outcomes.

Response based on the Investigator's 
Global Assessment (IGA) score of 
clear (0) or almost clear (1) (on a 5-
point scale) and a reduction from 
baseline of 2 points at all scheduled 
time points.

Response based on the Eczema Area 
and Severity Index 75% 
improvement from baseline 
(EASI-75) response at all scheduled 
time points.

Response based on at least 4 points 
improvement in the severity of Peak 
Pruritus NRS from baseline at all 
scheduled time points.

Response based on a 50% and 
90% improvement in the EASI 
total score (EASI-50 and EASI-90) 
at all scheduled time points.

Change from baseline in the 
percentage Body Surface Area 
(BSA) affected at all scheduled time 
points.
Safety Objective 
Safety Endpoints

To evaluate the safety and tolerability of 
abrocitinib during 12 weeks of 
treatment.

Incidence of treatment-emergent 
adverse events (TEAEs).

Incidence of serious AEs (SAEs). 


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•
Incidence of AEs leading to 
discontinuation.
•
Incidence of clinical abnormalities 
and changes from baseline in 
clinical laboratory values, and vital 
signs.
Tertiary/Exploratory Objectives
Tertiary/Exploratory Endpoints
•
 
 
 
 
 
 
•
To assess the effect of abrocitinib on 
Night Time Itch.
•
Changes from baseline in the Night 
Time Itch Scale at all scheduled time 
points.
•
 
 
 
 
 
 
 
 
 
 
 
The primary objective of this study is to assess the effects of abrocitinib on lesional and non-
lesional skin biomarkers of adult participants with moderate-to-severe AD. The following 
estimand attributes will be considered:
•
Population: Participants with moderate-to-severe AD as defined by the inclusion 
criteria;
•
Variable: Fold-change from baseline in the biomarkers for general inflammation 
(MMP12), hyperplasia (K16), type 2 helper T cell (Th2) immune response (CCL17, 
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CCL18, CCL26), and type 22 helper T cell (Th22) immune response (S100 calcium 
binding protein A [S100A8], S100A9, S100A12);
•
Intercurrent event: All data collected will be utilized;
•
Population-level summary: Mean fold-change from baseline within each treatment 
group.
Overall Design:
This is a randomized, double-blind, placebo-controlled, parallel-group, Phase 2a study to 
investigate the mechanism of action of abrocitinib by correlating efficacy outcomes with 
changes from baseline in key skin and blood biomarkers in adult participants ≥18 years of 
age with moderate-to-severe AD. Participants will be screened within 28 days prior to the 
first dose of study intervention to confirm study eligibility. A total of approximately 
51 participants will be randomized in a 1:1:1 ratio to receive abrocitinib 200 mg once daily 
(QD), abrocitinib 100 mg QD, or matching placebo QD for 12 weeks. 
The double-blind treatment period will last from Baseline/Day 1 to Week 12. Lesional skin 
biopsy (punch biopsy) collections are required at Baseline/Day 1 (Week 0), Day 29 
(Week 4), and Day 85 (Week 12), with an optional lesional skin biopsy collection at Day 15 
(Week 2). Non-lesional skin biopsy collection is required at Baseline/Day 1 (Week 0), with 
an optional non-lesional skin biopsy collection at Day 85 (Week 12).
The skin biopsy samples will be analyzed using immunohistochemistry (IHC) and gene 
expression by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), 
including Taqman Low Density Array (TLDA) PCR, for 48 genes including 2 housekeeping 
genes (18S and ribosomal protein lateral stalk subunit P0 [RPLP0]), as well as single gene 
PCR for a few genes that are often below detection level on TLDA. 
 
Blood for analyses of changes in inflammatory and cardiovascular markers will be collected 
at various time points.
 
Red 
Blood Cell and platelets derive from a common progenitor. Blood for platelet and red blood 
cell (RBC) counts will be collected and analyzed at all scheduled time points to characterize 
the potential mechanism by which platelet counts decrease in a dose-dependent and self-
limited manner after abrocitinib administration. OLINK proteomics will be used to analyze 
biomarkers in serum, including 4 panels of inflammatory and cardiovascular measures. 
At the end of the 12-week study treatment, qualified participants will have the option to enter 
the long-term extension (LTE) Study B7451015. Participants discontinuing early from this 
study will undergo a 4-week off-treatment follow-up period.
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Disclosure Statement:
This is a Parallel Treatment study with 3 Arms that is Investigator, sponsor, and participant 
blinded.
Number of Participants:
A total of approximately 51 participants will be randomized in the study. 
Intervention Groups and Duration:
Eligible participants will be randomized into 3 intervention groups in the study:
Group 1 (N=17): abrocitinib 200 mg QD for 12 weeks.
Group 2 (N=17): abrocitinib 100 mg QD for 12 weeks.
Group 3 (N=17): placebo QD for 12 weeks.
The total duration of participation in the study is up to 20 weeks, including up to 4 weeks for 
screening, 12 weeks study intervention, and a follow-up period of 4 weeks after study 
intervention (for those participants who do not enter the LTE study).
Data Monitoring Committee: Yes


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1.2. Schema


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1.3. Schedule of Activities (SoA)
Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit Window (days)
None
None
None
1
1
1
2
3
3
3
3
Enrollment Procedures
Informed consent
X
Register participant using 
IRT
X
See Section 6.3
Inclusion and exclusion 
criteria
X
X
See Section 5.1
and Section 5.2
Demographics, medical 
history, tobacco and 
alcohol history, AD disease 
history and prior AD 
treatments
X
See Section 8.2.1
Review prior/concomitant 
medications & treatments
X
X
X
X
X
X
X
X
X
X
X


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Provide patient emergency 
contact card
X
Medical Procedures
Complete physical 
examination 
X
X
See Section 8.2.1
Targeted physical exam
X
X
X
X
X
Vital signs (blood pressure, 
pulse rate, respiratory rate, 
temperature)
X
X
X
X
X
X
X
See Section 8.2.2
Weight
X
X
See Section 8.2.1
Height
X
See Section 8.2.1
Chest X-Ray
X
See Section 8.2.3
ECG (12-lead)
X
See Section 8.2.7
Laboratory Procedures


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Serum chemistry 
X
X
X
X
X
X
X
See Appendix 2. 
See Section 8.2.8
for guidance on 
abnormal lab 
results
Hematology including 
Reticulocyte Count and 
Coagulation panel.
X
X
X
X
X
X
X
X
See Appendix 2. 
See Section 8.2.8
for guidance on 
abnormal lab 
results
Lipid panel
X
X
8-hour fast 
required
 
Blood collection for 
biomarker evaluation –
Serum proteomics
X
X
X
X
See Section 8.8
See Section 8.8
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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
See Section 8.1.8
 
 
 
 
ee 
Section 8.5
Lymphocyte subsets 
X
X
X
X
X
X
See Appendix 2
Urinalysis 
X
X
X
X
X
X
X
See Appendix 2
Serum pregnancy test 
X
Required for all 
WOCBP
Urine Pregnancy Test 
(conducted at study site)
X
X
X
X
X
X
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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Banked Biospecimen 
Sample (Prep D1)
X
See Section 8.7.2
If not collected 
on the designated 
collection day, 
collect at the next 
available time 
point when 
biospecimens are 
being collected in 
conjunction with 
a participant visit.
Banked Biospecimen 
Sample (Prep B1.5) 
X
X
See Section 8.8.2
Banked Biospecimen 
Sample (Prep B2.5) 
X
X
See Section 8.8.2
Blood samples collection 
for viral studies
X
Only analyzed on 
suspected viral 
infection/reactiva
tion. See 
Section 8.2.8.2
HIV testing 
X
See Appendix 2


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Hepatitis B (HBsAg, 
HBsAb and HBcAb) and 
Hepatitis C (HCV Ab, 
HCV RNA)
X
See 
Section 8.2.8.1
HBV DNA (Only when 
HBsAg-, HBcAb+, 
HBsAb+ at screening)
X
X
See 
Section 8.2.8.1
Tuberculosis test
X
See Section 5.2
and Section 8.2.4
Study Treatment
Randomization
X
Drug dispensing
X
X
X
Drug accountability 
X
X
X
X


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Study intervention 
treatment
X-----------------------------------------------------------------------------------------------------X
At Weeks 4 and 
12, study 
intervention 
treatment should 
be taken at the 
study site to 
accommodate PK 
analysis. See 
Section 8.5
Assess eligibility for LTE 
Study B7451015
X
Clinical Assessments
Fitzpatrick Skin Type 
Assessment
X
See Section 8.2.6
Investigator’s Global 
Assessment (IGA)
X
X
X
X
X
X
X
See Section 8.1.6
Eczema Area and Severity 
Index (EASI)
X
X
X
X
X
X
X
See Section 8.1.7
Skin Biopsies


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Target lesion(s) 
identification
X
See Section 8.1.2
Lesional skin punch biopsy 
sampling
X
X 
(Optio
nal)
X
X
See Section 8.1.2
Non-lesional skin punch 
biopsy sampling
X
X 
(Optional)
See Section 8.1.2
Examination of Post-biopsy 
Site(s)
X
X
X
X
X
X
X
X
See Section 8.1.2
 
 
 
 
 
 
Photography
X
X
X
See Section 8.1.5
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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Patient-reported 
Outcomes (PRO)
Peak Pruritus Numerical 
Rating Scale (NRS)
X------X
X---------------------------------------------------X
X
X
X
X
See 
Section 8.1.9.1.
During screening, 
assessed for the 
7 days prior to 
Day 1 and also
each day from 
Day 1 to Day 15. 
Night Time Itch Scale
X------X
X---------------------------------------------------X
X
X
X
X
See 
Section 8.1.9.2.
During screening, 
assessed for the 
7 days prior to 
Day 1 and also
each day from 
Day 1 to Day 15. 
Safety
C-SSRS
X
X
X
X
X
See 
Section 8.2.9.1


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Screening
Intervention Period
Follow-up
Notes
Visit Identifier 
Day -28
Day 1
Week 0
Base 
line
Day 2
Week 
0
Day 4
Week
0
Day 8
Week
1
(by 
Phone
)
Day 15
Week
2
Day 29
Week
4
Day 4
3
Week
6
(by 
Phone
)
Day 5
7
Week
8
Day 85
Week 12
(EOT/ET) 
Day 113
Week 16
(EOS)
Visit 11 is 
4 weeks after last 
dose in case of 
early study 
termination. 
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
PHQ-8
X
See 
Section 8.2.9.2
Serious and non-serious 
adverse event monitoring
X
X
X
X
X
X
X
X
X
X
X
Contraception check
X
X
X
X
X
X
X
X
X
X
X
Required for all 
females
Abbreviations: AD = atopic dermatitis; C-SSRS = Columbia Suicide Severity Rating Scale; EASI = Eczema Area and Severity Index, ECG = electrocardiogram; EOS = End of 
Study, EOT = End of Treatment; ET= early termination; HBsAg = hepatitis B surface antigen; HBsAb = hepatitis B surface antibody; HBcAb = hepatitis B core antibody; HBV 
DNA = hepatitis B viral deoxyribonucleic acid, HCV Ab = hepatitis C antibody; HCV RNA = hepatitis C viral ribonucleic acid; HIV = human immunodeficiency virus; 
 
, IGA = Investigator’s Global Assessment; IRT = Interactive Response System; LS = lesional; LTE = long-term extension; NL = non-
lesional; NRS = Numerical Rating System; PHQ-8 = Patient Health Questionnaire - 8 Items; PK = Pharmacokinetic; WOCBP = women of childbearing potential.
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2. INTRODUCTION
Abrocitinib is a Janus kinase 1 (JAK1) inhibitor that is being investigated as a treatment for 
patients with moderate-to-severe AD. 
The Janus kinase (JAK) family, including JAK1, JAK2, JAK3, and tyrosine kinase 2
(TYK2), is a group of cytoplasmic tyrosine kinases that mediate signal transduction via 
interactions with Type 1 and Type 2 cytokine receptors critical for leukocyte activation, 
proliferation, survival, and function. Cytokine receptors demonstrate restricted association 
with JAKs such that different receptors or receptor classes preferentially utilize a given JAK 
dimer combination to transduce their signal. JAK1 pairs with JAK3 to mediate -common 
cytokine signaling and also with JAK2 or TYK2 to transmit the signals of additional 
cytokines important in inflammation and immune responses, including interleukin (IL)-4, 
IL-5, IL-6, IL-13, IL-21, IL-31, interferon-gamma (IFN-), and IFN-alpha (IFN-). JAK2 
homodimers are critical for the signaling of hematopoietic cytokines and hormones, 
including thrombopoietin (TPO), erythropoietin (EPO), IL-3, granulocyte-macrophage 
colony-stimulating factor, and prolactin. IL-12, EPO, and IL-23 are dependent on TYK2 and 
JAK2 for transmitting their signals.
Following cytokine activation, receptor-associated JAKs are phosphorylated and in turn 
phosphorylate specific sites on the receptor intracellular domain. Phosphorylation of specific 
sites on the intracellular domain of the receptor allows for the recruitment of signal 
transducers and activators of transcription (STATs) that can subsequently be phosphorylated 
by JAKs. Phosphorylated STAT molecules are released from the receptor, translocate to the 
nucleus where they bind to specific sites on deoxyribonucleic acid (DNA), and regulate gene 
transcription. 
The inflammatory skin disorder AD is characterized by epidermal barrier dysfunction and 
active AD lesions are accompanied by underlying immune activation.1,2,3 Skin lesions have 
shown increased infiltration by T cells, dendritic cells (DCs), and eosinophils; increased 
production of cytokines and chemokines; and reactive epidermal hyperplasia, in which 
epidermal differentiation products (ie, filaggrin and loricrin) are highly suppressed.4,5,6
Although AD has been classified as a Th2-dominated disease, other T-cell subsets (eg, Th22, 
Th17, and Th1 cells) might also contribute to pathogenesis.2,3 Key cytokines implicated in 
the pathophysiology of AD include IL-4, IL-5, IL-13, IL-31, and IFN-. These cytokines 
require JAK1 for signal transduction suggesting that selective JAK1 inhibitors, which 
modulate the activity of these cytokines, represent a compelling approach to the treatment of
inflammatory skin diseases such as AD.7
Data from a Phase 2b proof of concept (POC) study (B7451006) that evaluated participants 
with moderate-to-severe AD showed positive efficacy with the JAK1 inhibitor abrocitinib, as 
well as an acceptable safety profile, sufficient to support further clinical development in a 
larger Phase 3 program. Abrocitinib is an orally bioavailable small molecule that selectively 
inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site. Abrocitinib has a 
high degree of selectivity in vitro against other kinases: 28-fold selectivity over JAK2, 
>340-fold over JAK3 and 43-fold over TYK2, as well as a good selectivity profile over the 
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Abrocitinib Involvement in Hematopoiesis
In Study B7451006 there were dose-dependent decreases in mean platelet counts in the 
abrocitinib 200 mg once daily (QD) and 100 mg QD doses with a nadir at Week 4 (200 mg 
QD: -29.84%; 100 mg QD: -11.42%). Platelet counts resolved on treatment and returned to 
baseline by 4 weeks after end of treatment. The majority of participants maintained platelet 
counts within the normal range. No participant had an AE related to sequelae from 
thrombocytopenia (ie, bleeding or bruising). In addition, changes in total reticulocytes
(absolute) were observed in all treatment groups, but were generally not clinically relevant.
The abrocitinib 200 mg QD group had the greatest mean percent change from baseline in 
reticulocytes, for which decreases from baseline were observed during Week 1 to Week 6 
with a maximal decrease at Week 2, and increases from baseline were observed during 
Week 8 to Week 16.
The human body produces and removes 1011 platelets daily to maintain a normal steady-state 
platelet count. Platelet production must be tightly regulated to avoid spontaneous bleeding or 
arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet 
removal and production in physiological and pathological conditions. Production of red 
blood cells (RBCs) is a highly regulated process; however, the time of RBCs in circulation is 
longer (approximately 120 days) than that of platelets (8-9 days). Reticulocytes (immature 
RBCs that mature to RBCs in 2-3 days) have a shorter time, and as such, may be a more 
sensitive indicator of JAK inhibition on RBC production. Both platelets and RBC derive 
from the same progenitor. Hence, changes in one compartment can affect the other.
The Ashwell-Morrell receptor (AMR) recognizes senescent, desialylated platelets under 
steady-state conditions.8 Desialylated platelets and the AMR are the physiological ligand-
receptor pair regulating hepatic TPO messenger ribonucleic acid (mRNA) production, 
resolving the longstanding question of steady-state TPO regulation. The AMR-mediated 
removal of desialylated platelets regulates TPO synthesis in the liver by recruiting JAK2 and 
STAT3 to increase thrombopoiesis. Inhibition of TPO production downstream of the hepatic 
AMR-JAK2 signaling cascade could additionally contribute to thrombocytopenia associated 
with JAK1/2 treatment.
2.1. Study Rationale
Abrocitinib is being developed as an oral treatment for patients with moderate-to-severe AD 
based on the clinical results obtained in Phase 1 and Phase 2 studies. Additional information 
for the Phase 1 and Phase 2 study results previously completed may be found in the 
Investigator’s Brochure (IB). Phase 3 studies are ongoing to evaluate abrocitinib as 
monotherapy or when co-administered with background medicated topical therapy in adults 
or adolescents with AD.
This study (B7451037) is designed specifically to evaluate abrocitinib monotherapy in adults 
with AD to characterize the mechanism of action of abrocitinib and assess the effects of 
abrocitinib on the molecular signature of JAK1 inhibition in lesional and non-lesional skin 
and its correlation to clinical efficacy outcomes. The JAK1 AD Study B7451006 showed 
dose-dependent, self-limited decrease in platelet counts, but did not provide any mechanistic 


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insights.
 
 
 
 
 
2.2. Background
Atopic dermatitis, also known as eczema, is a common, chronic, inflammatory skin disorder 
characterized by flaky skin lesions, intense pruritus, and a general deterioration in quality of 
life. Over the past 50 years, AD has become more prevalent, especially in industrialized, 
temperate countries such as the United States (US).9,10 AD is one of the most common, 
chronic, relapsing childhood dermatoses, impacting 15-30% of all children in the US and 
many have disease that persists into adulthood. Earlier reports indicated that, in up to 70% of 
cases, the disease greatly improved or resolved by late childhood, however more recent 
findings suggest that disease activity remains manifest for a prolonged period of time. Based 
on a total of 7157 patients enrolled in the Pediatric Eczema Elective Registry (PEER) study, 
comprising a total of 22,550 person-years, it was concluded that symptoms associated with 
AD seem to persist well into the second decade of life and likely longer.11 The majority of 
studies conducted across multiple age groups suggest a continued decrease in prevalence 
with older age.12 Adult-onset AD does also occur, though it is less common. The prevalence 
of AD in adults is estimated to be approximately 10%.13
Although much progress has been made in understanding the causes of AD, the complex 
pathophysiology of AD is still not completely understood. It has been established that the 
pathophysiology of AD includes a defective skin barrier function, abnormal immune 
responses, defective antimicrobial immune defense, and a genetic predisposition. The 
predominant symptoms of AD, pruritus and the resulting scratching, typically sets off an 
amplification cycle of atopic skin inflammation. Activation of T lymphocytes, dendritic cells, 
macrophages, keratinocytes, mast cells, and eosinophils results in a release of numerous 
pro-inflammatory cytokines and chemokines. This amplification cycle sustains the 
inflammatory responses characteristic of the AD lesions.14
Non-medicated topical therapies include emollients. Medicated topical therapies for 
moderate-to-severe AD include topical corticosteroids (TCS) and topical calcineurin 
inhibitors (TCI) (eg, pimecrolimus, tacrolimus). Additional treatments generally reserved for 
severe AD include phototherapy (eg, ultraviolet A light [UVA] with or without psoralen, 
ultraviolet B light [UVB] narrowband or broadband) and systemic agents.15 For AD patients 
not responding to medicated topical therapies and phototherapy, on- and off-label use of 
systemic agents, which include oral corticosteroids, oral immunosuppressants, or the 
injectable human monoclonal antibody targeting IL-4 and IL-13, dupilumab, remain the last 
viable AD treatment options.
Currently available therapies for the treatment of AD have multiple limitations and 
drawbacks. For example, TCI have a limited role as a second-line treatment, due to their 
limitations in terms of the duration of treatment and the body region of treatment, and safety 
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concerns with malignancies. Also, systemic therapy options are associated with potentially 
severe adverse effects and require careful monitoring; therefore, the use of these agents is 
limited to short courses or intermittent therapy. Furthermore, the globally approved dosing 
for dupilumab as an initial dose of 2 × 300 mg subcutaneous injection followed by 300 mg 
every other week injections may limit the desirability of this route of treatment.
Of the currently available therapies, none offers a cure; therefore, the main aims of existing 
treatments are to reduce the occurrence of acute flares, to increase the time between relapses, 
and to reduce pruritus and the resulting sleep disturbance.16,17
Abrocitinib is an orally active JAK1 inhibitor that has demonstrated clinical efficacy in the 
Phase 2 Study B7451006. As mentioned above, a variety of pro-inflammatory cytokines such 
as IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), IL-31 and IFN-, have been 
suggested to have a role in the pathogenesis of AD. Many of these pathogenic cytokines use 
JAK1 for signaling. Therefore, JAK1 is an attractive therapeutic target for AD. However, a 
dose-dependent platelet decrease has been observed during the JAK1 development program, 
and the mechanism causing this is poorly understood. Data from this study will describe the 
molecular signature of JAK1 inhibition in healthy and AD lesional skin, as well as 
investigating the mechanism by which abrocitinib might decrease platelet counts in 
participants with moderate-to-severe AD.
2.2.1. Non-Clinical and Phase 1 Data
Data from nonclinical and Phase 1 programs supports the planned clinical trials with 
abrocitinib and further information is in the current version of the IB.
2.2.2. Phase 2b in AD (B7451006)
B7451006 was a Phase 2b proof-of-concept trial in 269 adults (ages 18-75) with 
moderate-to-severe AD investigating doses of 10, 30, 100, and 200 mg abrocitinib or placebo 
taken once daily for up to 12 weeks. The primary endpoint was the proportion of participants 
achieving an Investigator’s Global Assessment (IGA) score of clear (0), or almost clear (1), 
and a 2-point improvement from baseline at Week 12. The baseline was defined as the IGA 
score on Day 1 pre-dose. 
At Week 12, IGA response rates of the abrocitinib 200 mg and 100 mg dose groups were 
significantly greater than the placebo group, 44.5%, 27.8% and 6.3%, respectively. As a 
result, the estimated differences from placebo in the 200 mg and 100 mg groups were 38.2% 
(P=0.0032) and 21.5% (P=0.0184), respectively. The percent change from baseline in 
Eczema Area and Severity Index (EASI) scores at Week 12 were significantly higher for 
both the 200 mg and 100 mg groups compared to placebo, 63.7%, 41.6%, and 15.6% 
respectively. At Week 12, the proportion of participants achieving EASI-75 response was 
15.6% in the placebo group, 63.7% in the 200 mg group and 41.6% in the 100 mg group. As 
a result, the difference from placebo was 41.8% (P<0.0001) for the 200 mg group and 26.0% 
(P=0.0043) in the 100 mg group. Response rates at Week 12 for the 10 mg and 30 mg groups 
were not significantly different from placebo.


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At Day 15, the proportion of response based on achieving Peak Pruritus numerical rating 
scale 4 points improvement from baseline (NRS4) of abrocitinib 100 mg and 200 mg dose 
groups was greater than placebo. The estimated proportion of Peak Pruritus NRS4 responses 
at Day 15 were 69.8%, 41.1% and 15.7% for 200 mg, 100 mg and placebo groups, 
respectively. 
Abrocitinib demonstrated a rapid onset of action. In the 200 mg group, IGA and EASI scores 
improved until Week 4 and Week 6, respectively, and maintained their effect through 
12 weeks of treatment. A key differentiating feature for the JAK1 inhibitor is rapid resolution 
of itch associated with AD. Significant separation from placebo was achieved for the Peak 
Pruritus numerical rating scale (NRS) score as early as 2 days after initiation of treatment for 
the 200 mg dose group.
Overall, the results demonstrated dose dependent increases in responses at Week 12 for key 
efficacy endpoints (IGA, EASI and Peak Pruritus NRS).
Abrocitinib was generally safe and well tolerated in this study. Overall, adverse events (AEs) 
and serious AEs (SAEs) were numerically higher in participants receiving abrocitinib 
compared to placebo, but did not appear to increase with dose. The most common AEs were 
in the Infections and infestations, skin and subcutaneous tissue disorders and Gastrointestinal 
disorders system organ class, and the majority of the AEs were mild. There were 2 cases of 
herpes zoster, one in the 10 mg group (not treatment-related), and one in the 30 mg group 
(treatment-related). In the AD Phase 2 Study B7451006, there were dose-dependent 
decreases in mean platelet counts in the 200 mg QD and 100 mg QD doses with a nadir at 
Week 4 (200 mg QD: -29.84%; 100 mg QD: -11.42%). Platelet counts were resolving on 
treatment and returned to baseline by 4 weeks after end of treatment. Further details of the 
clinical Phase 2 development program can be found in the IB.
2.2.3. Summary of Abrocitinib Clinical Pharmacokinetics
Abrocitinib was rapidly absorbed following single dose oral solution/suspension 
administration over the dose range 3 mg to 200 mg with time to maximum absorption (Tmax) 
ranging between 0.55 to 0.77 hours (B7451001). Median Tmax at doses of 400 mg and 
800 mg was 1.5 and 3.9 hours, respectively, which indicated slower absorption compared to 
lower doses. Abrocitinib showed a monophasic decline at dose <100 mg with biphasic 
profiles at doses ≥100 mg. Observed abrocitinib maximum plasma concentrations (Cmax) 
following the single dose administration generally increased in proportion to the dose from 
3 mg to 800 mg. In contrast, both area under the plasma concentration-time profile from time 
zero extrapolated to infinite time (AUCinf) and area under the plasma concentration-time 
profile from time zero to the time of the last quantifiable concentration (AUClast) were dose 
proportional in the range of 3 mg to 200 mg, while a greater than proportional increase was 
observed at doses of 400 and 800 mg. The arithmetic mean terminal phase half-life (t½) was 
1.9 to 4.9 hours.
Following QD administration over the dose range 30 mg to 400 mg and 100 mg and 
200 mg twice a day (BID) for 10 days, median Tmax ranged between 0.50 to 0.77 hours 
(B7451001). After attainment of Cmax, the disposition of abrocitinib was consistent with that 


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observed following single-dose administration, showing a biphasic decline following all but 
the lowest dose and an arithmetic mean terminal phase t½ between 2.8 to 5.0 hours. The 
observed accumulation ratio (Rac) for area under the curve over dosing interval tau (AUCtau) 
and Cmax following QD dosing was minimal (between 1.1 and 1.5), consistent with the 
prediction from t½. Urinary recovery of abrocitinib was low, with <5% of the dose recovered 
unchanged in urine across all doses and regimens in all cohorts.
At a single 800 mg dose, the geometric mean percent coefficient of variation (%CV) Cmax
(ng/mL) was similar in Western (n=5; 3819 [26]) and Japanese participants (n=10; 3660 
[48]). However, geometric mean AUCinf (ng*hr/mL) was 26% higher in Western participants 
(n=5; 27540 [35]) than that observed in Japanese participants (n=9; 21860 [43]) (B7451001).
Geometric mean (%CV) Cmax and AUCtau following multiple dose administration of 200 mg 
BID were 17% and 56% higher, respectively, in the Western participants (n=5) than in 
Japanese participants (n=6). 
Co-administration of 400 mg with food resulted in equivalent geometric mean AUCinf
between fasted and fed conditions and a small mean decrease (<5%) in Cmax. Overall, 
abrocitinib can be administered with or without food.
Plasma profiling from the [14C] abrocitinib human mass balance study (B7451008) indicated 
parent as the most prevalent circulating species (26%), with 3 major and more polar mono-
hydroxylated metabolites identified: PF-06471658 (3-hydroxypropyl, 11%), PF-07055087 
(2-hydroxypropyl, 12%), and PF-07054874 (pyrrolidinone pyrimidine, 14%).
2.2.4. Population Pharmacokinetics
Population pharmacokinetics (PK) analysis was conducted by pooling data from two Phase 1 
studies (B7451001, first-in-human study, and B7451004, relative bioavailability study) in 
healthy volunteers and the proof-of-concept study (B7451006) in AD patients. A total of 
2465 PK observations from 354 participants were included in the analysis and the data were 
described using a 2 compartment model with first-order absorption. The estimates of 
systemic clearance/fraction of dose absorbed (CL/F) and volume of distribution/fraction 
absorbed (V/F) were 44.8 L/hr and 147 L with inter individual variability (IIV) values 
of 63% and 35% (expressed as %CV), respectively. Apparent clearance (CL/F) of AD 
patients was estimated to be ~38% lower than that of healthy participants; residual variability 
was estimated to be higher in AD patients compared to the value in healthy participants (66% 
vs. 36% CV). Baseline body weight, race, age and sex were tested as covariates on clearance 
and did not appear to impact the PK of abrocitinib.
2.3. Benefit/Risk Assessment
There was clinically meaningful benefit demonstrated for abrocitinib 200 mg QD and 
100 mg QD in the Phase 2b POC study in adult participants with moderate-to-severe AD.
The potential risks of treatment include those that were noted in Phase 2b and/or those based 
on the known pharmacology of other well studied JAK inhibitors (such as tofacitinib) and 
include viral reactivation, serious and opportunistic infections, hematopoietic effects 
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Overall, there is a favorable benefit-risk profile to support the continued development into 
Phase 3 of abrocitinib for the treatment of participants with AD.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of abrocitinib is provided in the IB, which is the single reference 
safety document (SRSD) for this study.
3. OBJECTIVES, ESTIMANDS AND ENDPOINTS
Primary Objective
Primary Endpoint

To assess the effects of abrocitinib 
on lesional and non-lesional skin 
biomarkers of adult participants with 
moderate-to-severe AD.

Changes from baseline in AD 
biomarkers in skin, including 
biomarkers for general inflammation 
(MMP12), hyperplasia (K16), Th2 
immune response (CCL17, CCL18, 
CCL26), and Th22 immune 
response (S100A8, S100A9, 
S100A12).
Secondary Objectives
Secondary Endpoints

To evaluate the effect of abrocitinib 
on gene expression (evaluated by 
mRNA PCR and/or gene arrays).

Changes from baseline in gene 
expression (evaluated by mRNA 
PCR and/or gene arrays) over time 
in skin lesions.

To evaluate the effect of abrocitinib 
on inflammatory infiltrates (T-cell 
and dendritic cells) using 
immunohistochemistry (IHC) in skin 
biopsies.

Changes from baseline in cellular 
(T-cells and dendritic cells) markers 
using IHC in skin biopsies at various 
time points.

To evaluate the effect of abrocitinib 
on epidermal hyperplasia using IHC 
and RT-PCR in skin biopsies.

Changes from baseline in 
hyperplasia markers (thickness, 
K16, Ki67) in skin biopsies.

To assess the effect of abrocitinib on 
blood biomarkers (OLINK 
proteomic in serum).

Changes from baseline in blood 
biomarkers (OLINK proteomic 
microassay for inflammation and 
immune response in serum).

To assess changes in T-cell 
lymphocyte subset populations in 
blood using flow cytometry.

Changes from baseline in T-cell 
lymphocyte subset populations in 
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
To evaluate the effect of abrocitinib 
on pruritus and its correlation to 
IHC and genetic markers in lesional 
skin.

Response based on at least 4 points 
improvement in the severity of Peak 
Pruritus numerical rating scale 
(NRS) from baseline and change 
from baseline in IHC and genetic 
markers in lesional skin.
Efficacy Objective 
Efficacy Endpoints

To evaluate the effect of abrocitinib 
on clinical efficacy outcomes.

Response based on the Investigator's 
Global Assessment (IGA) score of 
clear (0) or almost clear (1) (on a 
5 point scale) and a reduction from 
baseline of 2 points at all scheduled 
time points.

Response based on the Eczema Area 
and Severity Index 75% 
improvement from baseline 
(EASI-75) response at all scheduled 
time points.

Response based on at least 4 points 
improvement in the severity of Peak 
Pruritus NRS from baseline at all 
scheduled time points.

Response based on a 50% and 
90% improvement in the EASI 
total score (EASI-50 and EASI-90) 
at all scheduled time points.

Change from baseline in the 
percentage Body Surface Area 
(BSA) affected at all scheduled time 
points.
Safety Objective 
Safety Endpoints

To evaluate the safety and tolerability of 
abrocitinib during 12 weeks of 
treatment.

Incidence of treatment-emergent 
adverse events (TEAEs).

Incidence of serious AEs (SAEs). 

Incidence of AEs leading to 
discontinuation.

Incidence of clinical abnormalities 
and changes from baseline in 
clinical laboratory values, and vital 
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Tertiary/Exploratory Objectives
Tertiary/Exploratory Endpoints
•
 
 
 
 
 
 
•
To assess the effect of abrocitinib on 
Night Time Itch.
•
Changes from baseline in Night 
Time Itch Scale at all scheduled time 
points.
•
 
 
 
 
 
 
 
 
 
 
 
The primary objective of this study is to assess the effects of abrocitinib on lesional and non-
lesional skin biomarkers of adult participants with moderate-to-severe AD. The following 
estimand attributes will be considered:
•
Population: Participants with moderate-to-severe AD as defined by the inclusion 
criteria;
•
Variable: Fold-change from baseline in the biomarkers for general inflammation 
(Matrix Metallopeptidase [MMP]12), hyperplasia (Keratin [K]16), Th2 immune 
response (C-C motif chemokine ligand [CCL]17, CCL18, CCL26), and Th22 immune 
response (S100 calcium binding protein A [S100A]8, S100A9, S100A12);
•
Intercurrent event: All data collected will be utilized;
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
Population-level summary: Mean fold-change from baseline within each treatment 
group.


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4. STUDY DESIGN
                    
4.1. Overall Design
This is a randomized, double-blind, placebo-controlled, parallel-group, Phase 2a study to 
investigate the mechanism of action of abrocitinib by correlating efficacy outcomes with 
changes from baseline in key skin and blood biomarkers in adult participants ≥18 years of 
age with moderate-to-severe AD. Participants will be screened within 28 days prior to the 
first dose of study intervention to confirm study eligibility. A total of approximately 
51 participants will be randomized in a 1:1:1 ratio to receive abrocitinib 200 mg QD, 
abrocitinib 100 mg QD, or matching placebo QD for 12 weeks. Refer to Section 1.2 for a 
study schema. 
The total duration of participation in the study is up to 20 weeks, including up to 4 weeks for 
screening, 12 weeks study intervention, and a follow-up period of 4 weeks after study 
intervention. Qualified participants completing 12 weeks of treatment with study intervention 
will have the option to enter the long-term extension (LTE) study B7451015. Participants 
discontinuing early from this study will undergo a 4-week off-treatment follow-up.
Participants who have chronic moderate-to-severe AD as defined per the inclusion criteria 
will be enrolled in this study. Eligible participants must have a documented history, within 
6 months of the screening visit, of inadequate response to treatment with medicated topical 
therapy, or must have required systemic therapies for control of their disease. Investigators, 
participants, and the sponsor study team will be blinded as to treatment group assignment. 
Prior to any study procedure the informed consent will be obtained at the screening visit.
Participants will be screened within 28 days prior to the first dose of study intervention to 
confirm study eligibility. During the screening period, treatments for AD will be washed out, 
as applicable, according to eligibility requirements. All treatments for AD must have been 
washed out prior to Day 1 (see Section 5.2). Participants who continue to meet eligibility 
criteria at baseline will undergo Baseline/ Day 1 assessments and will be randomized in a 
1:1:1 ratio to receive abrocitinib 200 mg (N=17) or abrocitinib 100 mg QD (N=17) or 
matching placebo QD (N=17) from Day 1. 
The double-blind treatment period will last from Baseline/Day 1 to Week 12. For all 
participants, one 4.5 mm skin biopsy (punch biopsy) will be collected from each target 
treatment area at the specified time points. Lesional skin biopsies will be collected at 
Baseline/Day 1 (Week 0), Day 29 (Week 4), and Day 85 (Week 12), with an optional 
lesional skin biopsy collection at Day 15 (Week 2). A non-lesional skin biopsy will be 
collected at Baseline/Day 1 (Week 0), with an optional non-lesional skin biopsy collection at 
Day 85 (Week 12).
 
 
 
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Biopsy samples will be used to perform gene expression by quantitative reverse transcriptase 
polymerase chain reaction (qRT-PCR), including Taqman Low Density Array (TLDA) PCR, 
for 48 genes including 2 housekeeping genes (18S and RPLP0), as well as single gene PCR 
for a few genes that are below detection level on TLDA (see Table 1).
 
Immunohistochemistry (IHC) analysis will be performed for cellular infiltrates, Keratin 16 
(K16) staining, and hematoxylin and eosin (H&E) staining.
Many of the genes to be analyzed in this study are considered key biomarkers associated with 
AD pathways. For this study, the following biomarkers were selected for the primary 
endpoint: general inflammation (MMP12), hyperplasia (K16), Th2 immune response 
(CCL17, CCL18, CCL26), and Th22 immune response (S100A8, S100A9, S100A12).
 
The efficacy outcomes (eg, IGA, EASI, % body surface area [%BSA], and peak pruritus 
numerical rating scale [PP-NRS]) are collected so that any associations between biomarker 
changes and these efficacy outcomes may be evaluated. The clinical improvement will be 
correlated with the suppression of individual immune pathways, cellular infiltrates, and 
changes in epidermal biomarkers. Differences between groups and changes from baseline 
will be estimated. Tests of hypotheses for differences between treatment groups will not be 
performed.
Safety will be assessed by physical exams, standard laboratory testing, and collection of AEs.
Refer to the Schedule of Activities for a complete list of assessments to be performed during 
the study.
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4.2. Scientific Rationale for Study Design
This study is part of the global clinical development program for abrocitinib investigating the 
safety and efficacy of doses of 200 mg QD and 100 mg QD. This study is designed to 
specifically evaluate the mechanism of action of abrocitinib in adults with AD. 
4.3. Justification for Dose
Dose selection for Phase 3 was based on efficacy and safety of abrocitinib from a 
dose-ranging Phase 2b study, B7451006 that evaluated a 20-fold dose range (10 mg to 
200 mg QD) in adults with moderate-to-severe AD. 
Specifically for this study, both doses used in the Phase 3 program (100 mg QD and 200 mg 
QD) were selected based on the observed efficacy and the separation observed between doses 
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in the IGA and of EASI responses, as well as the dose-dependent changes observed in 
different hematologic parameters from this study. The inclusion of both doses will enable the 
assessment of efficacy and safety outcomes, skin molecular signatures, and the impact on 
markers of hemostasis, platelet counts, and other cell types.
In Study B7451006, both the abrocitinib 200 mg QD and 100 mg QD doses demonstrated 
acceptable safety and tolerability. A dose-dependent decrease in the mean platelet count from 
baseline was observed with a nadir at Week 4 (Figure 1). At Week 4, the mean platelet count 
and the 90% confidence interval (CI) were within the normal reference range for the 100 mg 
dose and 200 mg dose. The mean platelet counts increased towards baseline after Week 4. In 
addition, there was a decrease in mean reticulocyte count in the 200 mg QD group with a 
nadir at Week 2 (-14.73%). The mean reticulocyte count returned to baseline on treatment by 
Week 8. Leukopenia, neutropenia, and thrombocytopenia were reported by 1 participant in 
the 200 mg group, all of which were moderate and treatment-related. The platelet level in this 
participant was less than 0.5 × lower limit of normal. There were no reported adverse clinical 
effects (eg, bleeding events) potentially associated with reduced platelet counts observed in 
Study B7451006. Further details are available in the IB.
Figure 1.
Mean (90% CI) Percent Change from Baseline Versus Time for Platelets
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including follow-up assessments after the End of Treatment (EOT) or rolled over 
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The end of the study is defined as the date of the last study visit shown in the Schedule of 
Activities for the last participant at the study sites.
5. STUDY POPULATION
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:
Age
1. Participant must be 18 years of age at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants who meet the following AD criteria:

Clinical diagnosis of chronic moderate-to-severe AD (also known as atopic 
eczema) for at least 1 year prior to Day 1 and has confirmed AD at the screening 
and baseline visits according to the Hanafin and Rajka criteria for AD20 (see 
Appendix 11).

Documented recent history (within 6 months before the screening visit) of 
inadequate response to treatment with medicated topical therapy for AD for at 
least 4 consecutive weeks or who have required systemic therapies for control of 
their disease.
NOTE: Medicated topical therapy is defined as a topical product that contains an 
active pharmaceutical ingredient indicated for the treatment of AD (irrespective of 
whether it is an over-the-counter [OTC] or prescribed product).

Moderate-to-severe AD (affected BSA 10%, IGA 3, EASI 16, severity Peak 
Pruritus NRS 4 at the baseline visit).
3. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun 
lamps or other ultraviolet (UV) light sources during the study.
4. If receiving concomitant medications for any reason other than AD, must be on a 
stable regimen, which is defined as not starting a new drug or changing dosage within 
7 days or 5 half-lives (whichever is longer) prior to Day 1 and through the duration of 
the study.
Sex
5. Male or Female
Contraception use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.


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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 definition in Appendix 4)
OR

Is a WOCBP (all female participants, regardless of whether or not they have 
experienced/reported menarche, are considered WOCBP unless they are 
permanently sterile or confirmed infertile). A WOCBP who is sexually active 
must use a contraceptive method that is highly effective, with a failure rate of 
<1%, as described in Appendix 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 (Appendix 2) serum pregnancy 
test at the screening visit. A urine pregnancy test with a sensitivity of at least 
25 mIU/mL, will be performed before the first dose of study intervention and at 
every site visit including the EOT and follow-up visits to confirm the participant 
has not become pregnant. 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. Capable of giving signed informed consent/assent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.


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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Other acute or chronic medical condition or laboratory abnormality that may 
increase the risk associated with study participation or study intervention 
administration or may interfere with the interpretation of study results and, in 
the judgment of the investigator, would make the participant inappropriate for 
entry into this study.
2. The participant must have a risk assessment done by a qualified Mental Health 
Professional (MHP) to assess whether it is safe to participate in the trial if the 
participant’s responses on any of the screening instruments or other screening 
information indicate: 

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 8.2.9);

Previous history of suicidal behaviors in the past 5 years: “Yes” answer 
(for events that occurred in the past 5 years) to any of the suicidal behavior 
items of the C-SSRS;

Any lifetime history of serious or recurrent suicidal behavior (non-suicidal 
self-injurious behavior is not a trigger for a risk assessment unless in the 
investigator’s judgement it is indicated);

Clinically significant depression: PHQ-8 when the total score is ≥ 15;

The presence of any current major psychiatric disorder that is not 
explicitly permitted in the inclusion/exclusion criteria;

In the investigator’s judgment a risk assessment or exclusion is required.
3. A current or past medical history of conditions associated with 
thrombocytopenia, coagulopathy, or platelet dysfunction.
4. Have increased risk of developing venous thromboembolism, e.g. deep vein 
thrombosis or pulmonary embolism:
a.
History of venous thromboembolism, or 
b. First-degree relative with unprovoked venous thromboembolism (i.e. 
without known underlying cause such as trauma, surgery, 
immobilization, prolonged travel, pregnancy, hormone use, or plaster 


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cast), that would suggest participant is at increased risk of inherited 
coagulation disorder (e.g. Factor V Leiden).
5. Currently have active forms of other inflammatory skin diseases, ie, not AD or 
have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis, lupus) 
at the time of Day 1 that would interfere with evaluation of AD or response to 
treatment.
6. Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior 
to the first dose of investigational product, or is expected to be vaccinated or 
to have household exposure to these vaccines during treatment or during the 6 
weeks following discontinuation of investigational product.
7. Have a history of any lymphoproliferative disorder such as Epstein Barr virus 
(EBV)-related lymphoproliferative disorder, history of lymphoma, leukemia, 
or signs or symptoms suggestive of current lymphatic or lymphoid disease.
8. Infection History:

Have a history of systemic infection requiring hospitalization, parenteral 
antimicrobial therapy, or as otherwise judged clinically significant by the 
investigator within 6 months prior to Day 1;

Have active chronic or acute skin infection requiring treatment with 
systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or 
antifungals within 2 weeks prior to Day 1, or superficial skin infections 
within 1 week prior to Day 1.

A participant known to be infected with human immunodeficiency virus 
(HIV), Hepatitis B, or Hepatitis C (Section 8.2.8.1).

Have a history (single episode) of disseminated herpes zoster or 
disseminated herpes simplex, or a recurrent (more than one episode of) 
localized, dermatomal herpes zoster.
9. Have a history of alcohol or substance abuse within 6 months prior to Day 1 
that in the opinion of the investigator will preclude participation in the study.
10. Have a known immunodeficiency disorder or a first-degree relative with a 
hereditary immunodeficiency.
11. Have any malignancies or have a history of malignancies with the exception 
of adequately treated or excised non-metastatic basal cell or squamous cell 
cancer of the skin, or cervical carcinoma in situ.
12. Have evidence of active or latent or inadequately treated infection with 
Mycobacterium tuberculosis (TB) as evidenced by any of the following:

A positive QuantiFERON-TB Gold (QFT-G) In-Tube test or positive 
Mantoux/Purified Protein Derivative (PPD)/ tuberculin skin test (if 
appropriate per Section 8.2.4) performed at or within the 12 weeks prior to 
Day 1 is exclusionary; a negative test is required for eligibility. QFT-G is 


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the preferred testing method. If the QFT-G test cannot be performed, or if 
the results cannot be determined by the reference laboratory to be either 
positive or negative, then participants may be screened using the PPD test 
with approval of the Pfizer clinician.

It is recommended that participants with a history of Bacille Calmette 
Guérin (BCG) vaccination be tested with the QFT-G test since the 
Mantoux/PPD/tuberculin skin test may be positive due to vaccination. 
A QFT-G or PPD skin test is not required if the participant has 
previously received a documented adequate course of therapy for 
either latent or active TB infection.

A negative QFT-G or PPD skin test is required unless the participant 
has previously received a documented adequate course of therapy for 
either latent (9 months of isoniazid in a locale where rates of primary 
multi-drug TB resistance are <5% or an acceptable alternative 
regimen) or active (acceptable multi-drug regimen) TB infection. If the 
current incidence rates of multi-drug resistant TB infection in the 
locale are unavailable, an adequate treatment regimen should be 
defined as the regimen recommended by the health ministry or expert 
panel in the locale;

Chest X-ray (or chest computed tomography scan, or magnetic 
resonance imaging [MRI]) taken at screening or 12 weeks prior to 
Day 1 with changes suggestive of active TB infection as determined 
by a qualified radiologist.

A history of either untreated or inadequately treated latent or active TB 
infection;

A participant who is currently being treated for active TB infection is 
to be excluded.
Prior/Concomitant Therapy
13. Require treatment with prohibited concomitant medication(s) (Section 6.5.2
and Appendix 7) or have received a prohibited concomitant medication within
the specified time frame prior to the first dose of study medication.
14. Receiving anticoagulant medication, such as heparin, low molecular weight 
(LMW)-heparin, warfarin, anti-platelets, novel oral anticoagulants (eg 
apixaban), antiplatelet medication (eg clopidogrel), or has a contraindication 
to skin biopsies, or medications known to cause thrombocytopenia, (unless 
considered safe to stop and washout for the duration of the study). 
Nonsteroidal anti-inflammatory drugs [NSAIDs] and low-dose acetyl salicylic
acid will not be considered antiplatelet therapy.


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15. Participants who have received prior treatment with any systemic JAK 
inhibitors.
16. Have received any of the following treatment regimens specified in the 
time frames outlined below:
Within 1 year of first dose of study intervention:

Prior treatment with non-B-cell-specific lymphocyte depleting agents/therapies 
(eg, alemtuzumab [CAMPATH], alkylating agents [eg, cyclophosphamide or 
chlorambucil], total lymphoid irradiation, etc). Participants who have received 
rituximab or other selective B lymphocyte depleting agents (including 
experimental agents) are eligible if they have not received such therapy for at 
least 1 year prior to study baseline and have normal cluster of differentiation (CD) 
19/20+ counts by fluorescence-activated cell sorting (FACS) analysis.
Within 12 weeks of first dose of study intervention:

Biologics: within 12 weeks of first dose of study intervention or 5 half-lives (if 
known), whichever is longer.
Within 6 weeks of first dose of study intervention:

Use of dupilumab. 
Within 4 weeks of first dose of study intervention: 

Use of oral immunosuppressive drugs (eg, cyclosporine A [CsA], azathioprine, 
methotrexate, systemic corticosteroids, mycophenolate-mofetil, IFN-) within 
4 weeks of first dose of study intervention or within 5 half-lives (if known), 
whichever is longer;
NOTE: Corticosteroid inhalers and intranasal sprays are permissible for 
participants receiving a stable dose.
NOTE: Ophthalmic corticosteroids are permissible for participants receiving a 
stable dose.

Use of CYP2C9 and CYP2C19 inducers within 5 half-lives of the inducer plus 
14 days prior to the first dose of study intervention. For example, the average 
half-life of Carbamazepine after repeat dosing is 15 hours. The washout period is 
calculated as the sum of 5 half-lives (approximately 3 days) and an additional 
14 days for a total of 17 days prior to the first dose of study intervention.
Note: Half-life refers to the half-life of the parent drug and its metabolites, which 
are inhibitors or inducers. The longest half-life should be used to calculate the 
period necessary to washout a medication prior to the first dose of study 
intervention. For example, fluoxetine and its metabolite norfluoxetine are both 


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inhibitors of CYP2C19. The terminal half-life of fluoxetine is up to 6 days. 
However, norfluoxetine has a longer half-life, up to 16 days. Therefore, the 
washout period should be calculated based on the 5 times the half-life of 
norfluoxetine (approximately 80 days) and an additional 14 days for a total of 
94 days prior to the first dose of study intervention.

Phototherapy narrowband UVB (NB-UVB) or broad band phototherapy;

Regular use (more than 2 visits per week) of a tanning booth/parlor;

Herbal medications with unknown properties or known beneficial effects for AD.
Within 1 week of first dose of study intervention:

Use of CYP2C9 and CYP2C19 inhibitors within 1 week of first dose of study 
intervention or within 5 half-lives (if known) of the inhibitor, whichever is longer.

Anti-platelet drugs. 
Note: low dose acetyl salicylic acid is permitted, for the purpose of cardiovascular 
prophylaxis, at the discretion of the investigator.
Within 72 hours of first dose of study intervention:

Topical treatments that could affect atopic dermatitis (eg, corticosteroids,
calcineurin inhibitors, tars, antibiotic creams, topical antihistamines).
Prior/Concurrent Clinical Study Experience
17. Participation in other studies involving investigational drug(s) within 8 weeks 
or within 5 half-lives (if known) whichever is longer, prior to study entry 
and/or during study participation.
18. Note: Any investigational or experimental therapy taken or procedure 
performed for AD, psoriasis, psoriatic arthritis, or rheumatoid arthritis in the 
previous 1 year should be discussed with the Pfizer clinician (or designee). 
Participants cannot participate in studies of other investigational or 
experimental therapies or procedures at any time during their participation in 
this study.
Diagnostic assessments
19. ANY of the following abnormalities in the clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a 
single repeat, if deemed necessary:

Absolute neutrophil count of <1.2 x 109/L (<1200/mm3);


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
Hemoglobin <10.0 g/dL or hematocrit <30%;

Platelet count of <150 x 109/L (<150,000/mm3);

Absolute lymphocyte count of <0.50 x 109 /L (<500/mm3);

Estimated creatinine clearance <40 mL/min based on the age 
appropriate calculation, or serum creatinine >1.5 times the upper limit 
of normal (ULN);

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
values >2 times the ULN;

Total bilirubin 1.5 times the ULN; participants with a history of 
Gilbert's syndrome may have a direct bilirubin measured and would be 
eligible for this study provided the direct bilirubin is ULN.
20. A Screening 12-lead electrocardiogram (ECG) that demonstrates clinically 
significant abnormalities requiring treatment (eg, acute myocardial infarction, 
serious tachy- or brady-arrhythmias) or that are indicative of serious 
underlying heart disease (eg, cardiomyopathy, major congenital heart disease, 
low voltage in all leads, Wolff Parkinson White syndrome) or criteria 
associated with Q wave interval (QT)/ Fridericia-corrected Q wave interval 
(QTcF) abnormalities including:

A marked prolongation of QTcF interval (>500 milliseconds [ms]) on 
the screening ECG.
Other Exclusions
21. In the opinion of the investigator the participant is not a candidate for skin 
biopsy due to potential for complications, including but not limited to 
increased bleeding risk associated with history of bleeding disorders (acquired 
or inherited); use of antithrombotic agents; blood dyscrasias; delayed wound 
healing; compromised nutritional status; or uncontrolled diabetes.
22. In the opinion of the investigator or sponsor, have any uncontrolled clinically 
significant laboratory abnormality that would affect interpretation of study 
data or the participant’s participation in the study.
23. Have undergone significant trauma or major surgery within 1 month of the 
first dose of study intervention.
24. Investigator site staff members directly involved in the conduct of the study 
and their family members, site staff members otherwise supervised by the 
investigator, or participants who are Pfizer employees, including their family 
members, directly involved in the conduct of the study.


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5.3. Lifestyle Considerations
1. On study visit days, participants must not take the dose of study intervention 
until instructed to do so by the investigator or designated study site staff.
2. On study visit days, showering or bathing is permitted prior to attending the 
study visit.
3. On study visit days, topical therapy (ie, non-medicated topical therapy, per 
protocol guidelines as described in Section 6.5.1) are not permitted to be 
applied prior to attending the study visit. Topical therapies are required to be 
applied after the visit (per protocol guidelines as described in Section 6.5.1).
4. At Weeks 4 and 12, study intervention treatment should be taken at the study 
site to accommodate PK analysis.
5. WOCBP participants who are sexually active must agree to use one highly 
effective method of contraception (as specified in Appendix 4), as applicable.
5.3.1. Meals and Dietary Restrictions
On study visit days (Day 1 and Week 12), participants must comply with fasting 
requirements for at least 8 hours prior to the visit. Water and permitted non-study 
medications are allowed (Section 8.2.8).
5.3.2. Caffeine, Alcohol, 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.
5.3.3. Surgery
During the study, no elective surgery is permitted. However, if the proposed procedure is not 
judged to have any significant impact on the participant’s study assessments and treatment, 
then their case may be discussed with the Pfizer clinician or designee and an allowance made 
for their continued participation. Preferably, elective surgery should occur before the study or 
be delayed until study participation is completed.
The Pfizer clinician 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. In general, 
planned surgical procedures should not be performed unless the study intervention has been 
discontinued for at least 28 days (unless otherwise advised by the Pfizer clinician or 
designee). The Pfizer clinician or designee should be notified as soon as possible if a 
participant undergoes a surgical procedure without first informing the study staff.


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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study. 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).
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once after discussion with Pfizer if they fail the screening evaluation for reasons 
related to incidental transitory conditions. Individuals for whom screen failure is related to 
failing the disease severity (including extent of disease) inclusion criterion and who 
subsequently experience worsening AD, which in the investigator’s judgement would make 
them eligible for participation, may be considered for re-screening. Such cases should be 
discussed with the Pfizer Medical Monitor (or designee) to determine if re-screening is 
appropriate.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
The interventions are abrocitinib (also known as PF-04965842) and placebo. Abrocitinib will 
be administered orally at doses of 100 mg or 200 mg given QD for 12 weeks based on 
treatment assignment. In addition, one treatment group will be assigned to receive 
abrocitinib-matching placebo.
See the Schedule of Activities for drug dispensing and accountability details.
6.1. Study Intervention(s) Administered
Abrocitinib 100 mg tablets and matching placebo will be provided by the sponsor.
ARM Name
     Abrocitinib 200 
mg QD         
Abrocitinib 100 mg 
QD         
Placebo
Intervention 
Name
Abrocitinib             
Abrocitinib
          
Placebo
Type 
Small molecule
Small molecule
Placebo
Dosage Form
Tablet
Tablet
Tablet
Dose Strength
100 mg         
    100 mg         
    0 mg         
Dosage
100 mg – 2 tablets
100 mg – 1 tablet
Placebo – 1 tablet
Placebo – 2 tablets
Route of 
Administration
Oral
Oral
Oral


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Sourcing
Provided centrally by 
the sponsor.
Provided centrally by 
the sponsor.
Provided centrally by 
the sponsor.
Packaging and 
Labeling
Study Intervention 
will be provided in 
bottles. Each bottle 
will be labeled as 
required per country 
requirement.
Study Intervention 
will be provided in 
bottles. Each bottle 
will be labeled as 
required per country 
requirement.
Study Intervention 
will be provided in 
bottles. Each bottle 
will be labeled as 
required per country 
requirement.
QD = once daily
6.2. Preparation/Handling/Storage/Accountability
1. 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.
2. 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.
3. 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).
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the Investigational Product (IP) Manual.
6.3. Measures to Minimize Bias: Randomization and Blinding
Blinded study 
using central 
randomization 
via IRT system.
Participants will be randomized into the study on Day 1 provided they 
have signed an informed consent document to participate in the study, 
have undergone all screening procedures, and have met all inclusion 
and none of the exclusion criteria for participation in the study at 
screening and Day 1. A computer-generated randomization schedule 
will be used to assign participants to the treatment groups using an 
Interactive Response Technology (IRT).
The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the 
user’s identification (ID) and password, protocol number, the 
participant number and the date of birth of the participant. The site 
personnel will then be provided with a treatment assignment and 
dispensable unit (DU) or container number when abrocitinib / placebo 
study intervention is being supplied via the IRT. Treatment 
assignment will be based on a central randomization list consisting of 


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randomly permuted blocks. The IRT system will provide a 
confirmation report containing the participant number and DU or 
container number assigned. The confirmation report must be stored in 
the site’s files. 
There is a 24 hour-a-day, 365 days-a-year IRT help desk available for 
any questions or issues. The study specific IRT reference manual will 
provide the contact information and further details on the use of the 
IRT. 
Note: The IRT is the source of the participant number. The IRT 
system will provide the participant number at the end of the first IRT 
participant transaction.
Blind Break (IRT)
Investigators, participants and the sponsor study team will be 
blinded as to treatment group. The study will be participant 
(including caregiver) and investigator blinded. At all times, 
treatment and randomization information will be kept confidential 
and will not be released to the investigator, the study staff, or the 
sponsor’s study team until following the conclusion of the study, 
with the exception described in this section. 
At the initiation of the study, the study site will be instructed on 
procedures for breaking the blind. Blinding codes should only be 
broken in emergency situations for reasons of participant safety. The 
method will be an electronic process. When the blind for a 
participant has been broken, the reason must be fully documented 
and entered on the Case Report Form (CRF). Whenever possible, 
the investigator should contact Pfizer before breaking the blind. If 
the blind is broken, the investigator should promptly inform the 
Pfizer Clinician. The participant for whom the blind has been 
broken will be discontinued from the study and undergo the early 
termination (ET) procedures.
6.4. Study Intervention Compliance
Participant compliance with study intervention will be assessed at each visit. Deviation(s) 
from the prescribed dosage regimen should be recorded in the electronic case report form 
(eCRF).
For self-administration of abrocitinib / placebo at home, compliance will be recorded by the 
participant. 


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When study intervention is administered at the study site (Weeks 4 and 12 to accommodate 
PK analysis), it will be administered under the supervision of study personnel.
Compliance with the dosing of study intervention will be monitored and verified by 
delegated site personnel through a combination of the accounting of unused study 
intervention returned by the participant at the study visits, review of the dosing diary, and 
discussion with the participant which will be documented in the source documents.
Study intervention should be taken in the morning. Participants should be instructed that if a 
dose is inadvertently missed then it should be taken as soon as remembered, but not within 
12 hours of the next scheduled dose. 
The following compliance cases will be considered medication errors and will be discussed 
with the sponsor for possible withdrawal from the study:

Participants interrupting study intervention for more than 4 consecutive days or for a 
total of more than 7 days between visits; 

Participants administering >8 tablets in one day or administering 4 tablets/day for 
4 consecutive days; 

Participants who have an overall compliance of <80% or >120% between visits.
Any deviation from protocol specified dosing should be recorded as a protocol deviation and 
the investigator or designee is to counsel the participant and ensure steps are taken to 
improve compliance. In addition, if the compliance deviation reaches the thresholds defined 
above it should also be recorded as a medication error (see Section 8.3.10).
6.5. Concomitant Therapy
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:

Dates of administration including start and end dates

Dosage information including dose and frequency
The Pfizer clinician should be contacted if there are any questions regarding concomitant or 
prior therapy.
Participants must abstain from taking new prescription or nonprescription drugs (including 
vitamins and dietary or herbal supplements) within 7 days or 5 half-lives (whichever is 
longer) before the start of study intervention until completion of the follow-up visit (see 
Appendix 7 for washout periods for CYP2C9 and CYP2C19 inhibitors and inducers), unless, 
in the opinion of the investigator and sponsor, the medication will not interfere with the 
study.


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Participants will abstain from all prohibited concomitant medications as described in 
Section 6.5.2 and Appendix 7, of the protocol. Medications that are taken in the 
Screening/Washout period (after informed consent is obtained and before the first dose of 
study intervention) will be documented as prior medications. Medications taken after the first 
dose of study intervention has been administered will be documented as concomitant 
medications. All concomitant medications taken during the study must be recorded in study 
records with indication (if AD), reference to any associated adverse event, dose, and start and 
stop dates of administration. Participants will be queried about concomitant medication 
(including topical medications and treatments, over-the-counter and prescription medications 
and treatments, and vaccinations) at each study visit. Any new concomitant medications or 
dose changes to current concomitant medications should be evaluated for potential new or 
worsening adverse events.
6.5.1. Permitted Concomitant Treatments
The following concomitant AD standard-of-care therapies are permitted during the study and 
will not be provided by the sponsor:

Oral antihistamines;

Topical non-medicated emollient.
The following concomitant standard-of-care medications for other conditions are permitted 
during the study:

Corticosteroid inhalers and intranasal sprays are allowed for stable asthma patients;

Ophthalmic corticosteroids are allowed for patients receiving a stable dose to treat 
rhinoconjunctivitis;

Low dose acetyl salicylic acid (100 mg QD) is permitted, for the purpose of 
cardiovascular prophylaxis, at the discretion of the investigator;

Acetaminophen/paracetamol may be used intermittently (not to exceed 1 g/day);

Vitamin and mineral supplements of standard potency are allowed in amounts not known 
to be associated with adverse effects (such as hypervitaminosis).
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, and 
purified food substances. Vitamins, minerals and purified food substances are allowed in 
amounts not known to be associated with adverse effects (eg, hypervitaminosis).
Unless prohibited by the protocol, participants may be administered any other medications 
necessary for the treatment of medical disorders as deemed necessary by the treating 
physician. The addition of concomitant medications or any change in the dosage should be 
limited to those considered medically essential.


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A participant who is receiving a permitted concomitant medication for any reason must be on 
a locally-approved medication and dose, and this must be documented in the CRF. 
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 eCRF.
6.5.2. Prohibited Medications and Treatments
Participants are required to discontinue and avoid using certain medications and treatments 
(see Inclusion Criteria and Exclusion Criteria and Appendix 7). 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 AD must be discontinued except oral 
antihistamines. 
Due to the potential to affect AD with ultraviolet light exposure, participants must also avoid 
prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet 
light sources during the study.
Participants who received prior treatment with systemic JAK inhibitors are to be excluded 
from the study.
Herbal medications with unknown properties or known beneficial effects for AD must be 
discontinued at least 4 weeks before the first dose of study intervention.
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
After consulting with the Pfizer clinician, the investigator will make a judgment on the 
ongoing eligibility of any participant with prohibited medication use during the study.
6.6. Dose Modification
Dose modification of the study intervention is not permitted in this study.
6.7. Intervention after the End of the Study
There is no intervention required by the protocol following the end of the study. Participants 
may enroll in the LTE study if eligible.


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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
     
7.1. Discontinuation of Study Intervention
In certain instances, it may be necessary for a participant to permanently discontinue study 
intervention (ie, study treatment). If study intervention is permanently discontinued, the 
participant will remain in the study to be evaluated for EOT assessments (per Schedule of 
Activities). 
Note that discontinuation of study treatment does not represent withdrawal from the study. 
Refer to Appendix 10 for discontinuation criteria.     
See the Schedule of Activities for data to be collected at the time of intervention 
discontinuation and follow-up and for any further evaluations that need to be completed.
7.1.1. Temporary Discontinuation
Temporary interruption to dosing is not allowed in this study, except when specified in the 
protocol for participant safety.
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;

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 Schedule of Activities 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.


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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.
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. 
Discontinuation of specific sites or of the study as a whole are handled as part of 
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8. STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the Schedule of Activities. 
Protocol waivers or exemptions are not allowed.

Immediate safety concerns 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 
Schedule of Activities, 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. Participants will be screened (Visit 1) 
within 28 days prior to administration of the study intervention to confirm that they 
meet the participant selection criteria for the study. The investigator (or an 
appropriate delegate at the investigator site) will obtain informed consent from each 
participant, in accordance with the procedures described in Section 10.1.3. 

Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF 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 Schedule of Activities.

Screening laboratory tests with abnormal results may be repeated once to confirm 
abnormal results; the last value will be used to determine eligibility. If results return 
to normal within the 4-week screening period, the participant may enter the study.

Due to possible need for PPD testing and chest radiograph, screening procedures 
may be performed over more than 1 visit in the 28 days prior to the Day 1 visit.

Visit windows are based on Day 1 visit. To assure consistency and reduce 
variability, all study visits should occur in the morning whenever possible. On days 
of study visits, participants will receive their dose at the clinic during the visit. 

Participants are required to fast for at least 8 hours prior to all visits that include 
lipid profile panel testing (Day 1 and Week 12). During the fasting period, 
participants should refrain from all food and liquids (water and permitted non-study 
medications are allowed). 

Urine pregnancy test must be performed prior to dosing with the study intervention 
for WOCBP through the EOT/EOS visit specified in the Schedule of Activities.

Prior to attending a study visit, participants are allowed to shower and bathe but 
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8.1. Efficacy Assessments
8.1.1. Rater Qualifications 
Clinical evaluations of AD will be performed by an experienced and qualified dermatologist 
(board certified or equivalent). An experienced and qualified non-dermatologist physician or 
experienced medical professional with experience in the conduct of dermatology clinical 
trials may be permitted to perform the clinical evaluations of AD when designated by the 
primary site Investigator. The evaluator must receive and document protocol specific and 
applicable efficacy assessment scales training prior to performing these evaluations. To 
assure consistency and reduce variability, the same evaluator must assess all 
dermatological clinical evaluations for any individual participant throughout the study 
whenever possible; a back-up experienced and qualified, protocol-trained evaluator will 
only be allowed and documented in case of emergency or special situations when the 
designated evaluator is unable to perform the evaluation.
8.1.2. Skin Biopsies
One 4.5 mm skin biopsy (punch biopsy) will be collected from each target lesional skin at 
Baseline/Day 1 (Week 0), Day 29 (Week 4), and Day 85 (Week 12), with an optional 
collection on Day 15 (Week 2). The target lesional skin to be used for skin biopsy should be 
selected pre-dose at the Baseline/Day 1 visit. An area of non-lesional skin anatomically 
similar in location to the target lesional skin should also be selected for biopsy on Day 1, 
with optional collection on Day 85. Biopsies at all time points following the visit at 
Baseline/Day 1 will always be collected from the same area, even if the target treatment area 
has cleared, in order to assess molecular clearance.
Ideally, a single target, approximately the size of the palm of the participant’s hand, should 
be identified and the location and borders noted in the clinic chart; anatomical markers 
should be used as needed to describe the target skin location. A photograph of the lesional 
and non-lesional site(s) will also be taken (see Section 8.1.5). The target skin should be of 
sufficient size to accommodate the required number of biopsies specified in the protocol 
(eg, 3 biopsies) while not interfering with the clinical evaluation of the lesion; the potential 
biopsy sites should be pre-selected. 
The biopsies after Day 1 will be collected in the vicinity of the torso (upper and mid back, 
chest), abdomen, buttocks, upper arms and upper legs, but at least 1 cm distant from where 
the biopsies were collected at Day 1, even if the target lesion has cleared. Target lesions may 
not be located on the head, face, neck, elbows, knees, lower arms, lower legs, genital area 
and inguinal area, intertriginous areas, and lower back. 
Each biopsy will be cut in half. One half will be used to perform reverse transcriptase 
polymerase chain reaction (RT-PCR) and gene array and the other half will be used for 
immunohistochemistry analysis.
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Tissue and derived material left over from the biopsy already being performed in this study 
may be used for potential further testing 
 provided material is 
available. Each sample will be labeled with a code so that the laboratory personnel (including 
biomarker laboratory personnel) testing the samples will not know the participant’s identity. 
Any tissue or derived material left over may be stored long term for further research purposes 
at a Sponsor-designated facility. The samples will be used for the purposes described in the 
protocol and in the informed consent document; any other uses require additional ethical 
approval. Unless a time limitation is required by local regulations or ethical requirements, the 
samples may be stored for up to 15 years after the end of the study and then destroyed.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.1.5. Photography of Representative AD Lesions
For participants, photographs of treated AD will be obtained (according to the separately 
provided Photography Instructions) at various time points as described in the Schedule of 
Activities. Areas photographed should be recorded in source documents so that the same AD 
body region(s) will be photographed at each time point. Photographs may be optional and 
will be utilized for illustrative purposes and not formally evaluated as an endpoint for 
analysis.
Photographic services will be provided through a central photography laboratory selected by 
the sponsor. Detailed procedures to assure consistency will be provided separately in a 
central photography laboratory instruction manual.
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8.1.6. Investigator’s Global Assessment (IGA)
The Investigator’s Global Assessment of AD is scored on a 5-point scale (0-4), reflecting a 
global consideration of the erythema, induration, and scaling. The clinical evaluator of AD 
will perform an assessment of the overall severity of AD and assign an IGA score and 
category as described in Table 2. The assessment will be a static evaluation without regard to 
the score at a previous visit. Assessments will be collected at various time points as described 
in the Schedule of Activities.
Table 2.
Investigator’s Global Assessment (IGA) Score
Score
Category
Description
0
Clear
Atopic dermatitis is cleared, except for any residual discoloration 
(post-inflammatory hyperpigmentation and/or hypopigmentation).
1
Almost 
Clear
Overall, the atopic dermatitis is not entirely cleared and remaining lesions 
are light pink (not including post inflammatory hyperpigmentation) and/or; 
have barely palpable hard thickened skin and/or papules and/or; have barely 
perceptible lichenification; excoriation and oozing/crusting are absent.
2
Mild
Overall, the atopic dermatitis consists of lesions that are light red; with 
slight, but definite hard thickened skin and/or papules; with slight, but 
definite linear or picked scratch marks or penetrating surface injury; with 
slight, but definite thickened skin, fine skin markings, and lichenoid scale; 
oozing/crusting is absent.
3
Moderate
Overall, the atopic dermatitis consists of lesions that are red; with easily 
palpable moderate hard thickened skin and/or papules; with moderate linear 
or picked scratch marks or penetrating surface injury; with moderate 
thickened skin, coarse skin markings, and coarse lichenoid scale; with slight 
oozing/crusting.
4
Severe
Overall, the atopic dermatitis consists of lesions that are deep, dark red; with 
severe hard thickened skin and/or papules; with severe linear or picked 
scratch marks or penetrating surface injury; with severe thickened skin with 
very coarse skin markings and lichenoid scale; with moderate-to-severe 
oozing/crusting.
8.1.7. Eczema Area and Severity Index (EASI)
The EASI quantifies the severity of a participant’s AD based on both severity of lesion 
clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD 
clinical evaluator of the degree of erythema, induration/papulation, excoriation, and 
lichenification (each scored separately) for each of four body regions, with adjustment for the 
percent of BSA involved for each body region and for the proportion of the body region to 
the whole body. Assessments will be collected at various time points as described in the 
Schedule of Activities.
Lesion Severity by Clinical Signs: The basic characteristics of AD lesions—erythema, 
induration/papulation, excoriation, and lichenification—provide a means for assessing the 
severity of lesions. Assessment of these four main clinical signs is performed separately for 


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four body regions: head and neck, upper limbs, trunk (including axillae and groin) and lower 
limbs (including buttocks). Average erythema, induration/papulation, excoriation, and 
lichenification are scored for each body region according to a 4 point scale: 0 = absent; 
1 = mild; 2 = moderate; 3 = severe. Morphologic descriptors for each clinical sign severity 
score are shown in Table 3.
Table 3.
Clinical Sign Severity Scoring Criteria for the Eczema Area and Severity 
Index (EASI)
Score
Description
Erythema (E)
0
Absent
None; may have residual discoloration (post-inflammatory 
hyperpigmentation and/or hypopigmentation).
1
Mild
Light pink to light red
2
Moderate
Red
3
Severe
Deep, dark red
Induration/Papulation (I)
0
Absent
None
1
Mild
Barely palpable to slight, but definite hard thickened skin and/or 
papules
2
Moderate
Easily palpable moderate hard thickened skin and/or papules
3
Severe
Severe hard thickened skin and/or papules
Excoriation (Ex)
0
Absent
None
1
Mild
Slight, but definite linear or picked scratch marks or penetrating 
surface injury
2
Moderate
Moderate linear or picked scratch marks or penetrating surface 
injury
3
Severe
Severe linear or picked scratch marks or penetrating surface 
injury
Lichenification (L)
0
Absent
None
1
Mild
Barely perceptible to slight, but definite thickened skin, fine skin 
markings, and lichenoid scale
2
Moderate
Moderate thickened skin, coarse skin markings, and coarse 
lichenoid scale
3
Severe
Severe thickened skin with very coarse skin markings and 
lichenoid scale
Percent BSA with Atopic Dermatitis: The number of handprints of skin afflicted with AD 
in a body region can be used to determine the extent (%) to which a body region is involved 
with AD (Table 4). When measuring, the handprint unit refers to the size of each individual 
participant’s hand with fingers in a closed position.


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Table 4.
Handprint Determination of Body Surface Area (BSA)
Body Region
Total Number of 
Handprints in Body 
Region*
Surface Area of Body 
Region Equivalent of One 
Handprint*
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae and 
groin/genitals)
30
3.33%
Lower Limbs (including 
buttocks)
40
2.5%
Handprint refers to the hand size of each individual participant.
* The number of handprints will be for the entire body region.
The extent (%) to which each of the 4 body regions is involved with AD is categorized to a 
numerical Area Score using a non-linear scaling method according to the following BSA 
scoring criteria (Table 5).
Table 5.
Eczema Area and Severity Index (EASI) Area Score Criteria
Percent BSA with Atopic Dermatitis in a Body Region
Area Score
0%
0
>0 - <10%
1
10 - <30%
2
30 - <50%
3
50 - <70%
4
70 - <90%
5
90 - 100%
6
Body Region Weighting: Each body region is weighted according to its approximate 
percentage of the whole body (Table 6).
Table 6.
Eczema Area and Severity Index (EASI) Body Region Weighting
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and 
groin/genitals)
0.3
Lower Limbs (including buttocks)
0.4
In each body region, the sum of the Clinical Signs Severity Scores for erythema, 
induration/papulation, excoriation, and lichenification is multiplied by the Area Score and by 


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the Body Region Weighting to provide a body region value, which is then summed across all 
four body regions resulting in an EASI score as described in Equation 3.
Equation 3: EASI = 0.1Ah(Eh+Ih+Exh+Lh) + 0.2Au(Eu+Iu+ExU+Lu) + 
0.3At(Et+It+Ext+Lt) + 0.4Al(El+Il+Exl+Ll)
A = Area Score; E = erythema; I = induration/papulation; Ex = excoriation; 
L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs
The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores 
representing greater severity of AD.
8.1.7.1. Body Surface Area – Efficacy (BSA Efficacy)
BSA Efficacy will be derived from the sum of the BSA in handprints across 4 body regions 
assessed as part of the EASI assessment (Table 4). Handprint refers to that of each individual 
participant for their own measurement. The BSA Efficacy ranges from 0 to 100%, with 
higher values representing greater severity of AD. Assessments will be collected at various 
time points as described in the Schedule of Activities.
 
 
8.1.9. Patient-reported Outcomes (PROs)
Participants will complete the PROs at the clinic prior to other clinical activities and study 
intervention administration. The PROs should be checked for completeness by the study site 
staff before proceeding with other steps of the clinical visit procedures. Compliance with 
scheduled PROs activities will be monitored. Delegated site staff will oversee the 
administration of PROs at site visits to ensure protocol compliance. Participants are given a 
diary to complete the Peak Pruritus NRS and Night Time Itch Scale on a daily basis. 
Delegated site staff will review compliance at each visit and counsel as appropriate. If a 
participant has repeated non-compliance, the participant should be re-trained. 
 
8.1.9.1. Peak Pruritus Numerical Rating Scale (NRS)
The severity of itch (pruritus) due to AD will be assessed using the Peak Pruritus NRS, a 
validated horizontal NRS.21,22 Participants will be asked to assess their worst itching due to 
AD over the past 24 hours on an NRS anchored by the terms “no itch” (0) and “worst itch 
imaginable” (10). This item will be administered to all participants. Participants will enter 
Peak Pruritus NRS assessment into a diary. The Peak Pruritus NRS as it is assessed on the 
day of the baseline visit will be included in the evaluation of Inclusion Criterion 2.
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The Peak Pruritus NRS should be completed as per Schedule of Activities.
8.1.9.2. Night Time Itch Scale 
Severity of Night Time Itch
The severity and frequency of itch (pruritus) during the night due to AD will be assessed 
using the Night Time Itch Scale. Participants will be asked to assess their worst itching due 
to AD during their most recent night’s sleep on an NRS anchored by the terms “no itch” (0) 
and “worst itch imaginable” (10). The frequency of itch will be assessed using a 5-point 
qualitative scale, with responses including “Never”, “Rarely”, “Sometimes”, “Often” and 
“Almost Always”. This item will be administered to all participants. 
The Night Time Itch Scale should be completed as per Schedule of Activities.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities.
8.2.1. Physical Examinations and Medical History

Complete AD disease history includes collection of details of AD at Screening: AD 
diagnosis, the use of topical treatments, systemic treatments and other treatments for 
AD. Medical history in addition to AD history including disease duration will be 
collected at screening. Medical history also includes history of alcohol and tobacco 
use. Smoking status and average weekly alcohol consumption (units/week) will be 
collected, where a unit contains 12 g of pure alcohol, an amount equivalent to that 
contained in 5 oz/150 mL (a glass) of wine, 12 oz/360 mL of beer, or 1.5 oz/45 mL 
of 90 proof of spirits. 

Complete medication history of all prescription or nonprescription drugs, and dietary 
and herbal supplements taken within 28 days prior to the planned first dose, except as 
noted below: 
The following timeframe prior to the planned first dose must be used for collection of 
the following Current/Prior Medications:

1 year: Previous non-systemic drug treatments for AD including topical 
treatments; 

Lifetime history of previous systemic treatment for AD and reason for stopping 
any systemic treatment for AD;

Lifetime history of intolerance/allergy to any drug, regardless of indication.

A complete physical examination will include, at a minimum, assessments of the 
general appearance; skin; head, eyes, ears, nose and throat (HEENT); mouth, heart; 


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lungs; breast (optional); abdomen; external genitalia (optional); extremities; 
neurologic function; and lymph nodes. Complete physical examinations must be 
performed by the investigator, sub-investigator or a qualified health professional per 
local guidelines. Height (inches or centimeters) and weight (lbs. or kg) will be 
measured and recorded in the source document at the screening visit. Height and 
weight will be measured without the participant wearing shoes. Weight (lbs. or kg) 
will continue to be measured and recorded at various time points described in the 
Schedule of Activities.

A targeted physical examination will include, at a minimum, assessments of the 
skin, heart, lungs, and abdomen and examination of body systems where there are 
symptom complaints by the participant. Targeted physical examinations must be 
performed by the investigator, sub-investigator or a qualified health professional per 
local guidelines.

Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.2.2. Vital Signs

Vital signs (sitting blood pressure, pulse rate, respiratory rates, and temperature) 
will be measured after 5 minutes of rest as indicated in the Schedule of Activities.

Pulse rate and blood pressure will be assessed pre-dose. The same method should be 
used consistently throughout the study. 

Pulse rate and blood pressure measurements will be assessed in a seated position, 
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.

Pulse rate and blood pressure measurements should be preceded by at least 5 
minutes of rest for the participant in a quiet setting without distractions (eg, 
television, cell phones). Participants should refrain from smoking or ingesting 
caffeine during the 30 minutes preceding the measurements. 
8.2.3. Chest X-Ray
Chest X-ray (posterior-anterior and lateral views) or other appropriate diagnostic image (ie, 
chest computed tomography or MRI) at screening or within 12 weeks prior to Study Day 1. 
Such imaging must be read by a qualified radiologist and show no evidence of current, active 
TB. Documentation of the official reading must be located and available in the source 
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8.2.4. Tuberculosis Testing
At the time of screening, all participants will undergo tuberculosis (TB) testing unless 
performed within 12 weeks of Day 1. QFT-G is the preferred testing method. If the QFT-G 
test cannot be performed, or if the results cannot be determined by the reference laboratory to 
be either positive or negative, then participants may be screened using the PPD test with 
approval of the Pfizer clinician. 
In addition to TB testing as specified in this clinical protocol, a chest X-ray (or other 
appropriate diagnostic image (see Section 8.2.3) is recommended.
QFT-G test is an in vitro diagnostic test using a peptide cocktail simulating early secretory 
antigen 6 (ESAT-6), cell filtrate protein 10 (CFP-10), and TB 7.7 proteins to stimulate cells 
in heparinized whole blood. Detection of interferon-by Enzyme-Linked Immunosorbent 
Assay (ELISA) is used to identify in vitro responses to these peptide antigens that are 
associated with Mycobacterium tuberculosis infection. QFT-G is an indirect test for 
M. tuberculosis infection (including disease) and is intended for use in conjunction with risk 
assessment, radiography and other medical and diagnostic evaluations.
A blood sample (approximately 3 mL) will be collected at screening for QTF-G testing. 
Following sample processing, the sample will be shipped to the sponsor’s designated 
reference 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.
Should the PPD test be required, the test must be administered and evaluated by a health care 
professional 48 to 72 hours later, unless performed and documented within the last 3 months. 
The test should be performed according to local standards with induration of <5 mm required 
for inclusion.
8.2.5. Special Safety Assessment
In the event of a suspected opportunistic infection, effort should be made to identify the 
pathogen utilizing laboratory or other methods appropriate to the clinical situation. 
In case of a suspected viral skin infection (eg, herpes zoster, herpes simplex or eczema 
herpeticum), a specimen for viral DNA may be analyzed locally for confirmation and results 
provided to the adjudication committee to support evaluation. 
For participants with a past history of oral or genital herpes simplex virus infection and a 
presentation consistent to prior infections, further laboratory analysis may be performed at 
the discretion of the investigator. 
8.2.6. Skin Type Assessment
As part of baseline characteristics, a skin type assessment will be done using the Fitzpatrick 
Skin Type assessment (see Appendix 12). This is used to classify a person’s skin type by 
their response to sun exposure (ie, burning or tanning).


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8.2.7. Electrocardiograms

Single 12-lead ECG will be obtained using an ECG machine that automatically 
calculates the heart rate and measures PR, QRS, QT, and [QTc] intervals. Refer to 
Appendix 10 for [QTc] withdrawal criteria. ECGs will be done locally.

The ECG should be performed after the participant has rested quietly for at least 
10 minutes in a supine position. 

A participant’s screening ECG must not demonstrate clinically significant 
abnormalities prior to randomization.
8.2.8. Clinical Safety Laboratory Assessments

See Appendix 2 for the list of clinical laboratory tests to be performed and the 
Schedule of activities for the timing and frequency.

Participants must abstain from all food and drink (except water and non-study 
medications) for an 8-hour overnight fast prior to labs that include the lipid profile 
panel on Day 1 and Week 12. All other labs do not require fasting.

Sample collection, labeling, storage, and shipping information can be found in the 
laboratory manual.

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 after 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 Appendix 2, must be 
conducted in accordance with the laboratory manual and the Schedule of 
Activities.
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.


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8.2.8.1. Hepatitis Testing 
Hepatitis B testing: HB surface antigen (HBsAg), HB core antibody (HBcAb), HB surface 
antibody (HBsAb), HBV DNA. 
Interpretation of Hepatitis B Testing Results:
HBsAg negative and HBcAb negative: Participant is eligible for the study;
HBsAg positive and HBcAb negative: Participant is excluded from study participation;
HBsAg negative and HBcAb positive and HBsAb negative: Participant is excluded from 
study participation.
HBsAg negative and HBcAb positive and HBsAb positive: Participant may be eligible for 
the study:

Participants who are HBsAg negative, HBcAb positive, and HBsAb positive at Screening 
will have reflex testing for HBV DNA. Participants who have HBV DNA above lower 
limit of quantification (LLQ) will be excluded. Participants who are HBV DNA negative 
or below LLQ may be randomized but will have repeat HBV DNA testing at Week 12 (or 
Early Termination). 
Hepatitis C testing: Hepatitis C Antibody (HCV Ab), Hepatitis C Viral RNA (HCV RNA 
for confirmation of positive HCV Ab result). 
Interpretation of Hepatitis C Testing Results:
Participants who are positive for hepatitis C viral antibody (HCVAb) and HCV RNA will be 
screen failed.
8.2.8.2. Viral Studies 
Blood samples will be collected at Baseline for viral studies but will be analyzed only if the 
participant has suspected viral infection/reactivation. Additional sample collection 
instructions will be provided in the lab manual. The retained samples will be destroyed upon 
participant completion of this study or the LTE study. 
8.2.9. Suicidal Ideation (Columbia Suicide Severity Rating Scale)
Site staff is to administer the C-SSRS and PHQ-8 to all participants at screening and score 
immediately. The participant must have a risk assessment done by a qualified MHP to assess 
whether it is safe to participate in the trial if the participant's responses on any of the 
screening instruments or other screening information indicate:

Suicidal ideation associated with actual intent and a method or plan in the past year: 
“Yes” answers on items 4 or 5 of the C-SSRS.


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
Previous history of suicidal behavior in the past 5 years: “Yes” answer (for events 
that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS.

Any lifetime history of serious or recurrent suicidal behavior (non-suicidal self-
injurious behavior is not a trigger for a risk assessment unless it is indicated according 
to the investigator’s judgement).

Clinically significant depression when the PHQ-8 total score is ≥ 15.

The presence of any current major psychiatric disorder that is not explicitly permitted 
in the inclusion/exclusion criteria.

In the investigator’s judgement a risk assessment or exclusion is required.
Written documentation of the risk assessment should be included in the subject’s clinical 
record (source documentation).
At the baseline (randomization) visit, if there are “yes” answers on items 4, 5 or on any 
behavioral question of the C-SSRS, a risk assessment should be done prior to randomization 
by a qualified MHP to determine whether it is safe for the participant to continue in the trial. 
This risk assessment should be completed in a timeframe that would allow for the screening 
period to be completed within 28 days. A copy of the risk assessment should be included in 
the source documents.
At post-baseline visits, if there are “yes” answers on items 4, 5 or on any behavioral question 
of the C‑SSRS, a risk assessment by a qualified MHP should be done to determine whether it 
is safe for the participant to continue in the trial.
Participants who have recurrent SIB during the trial must be discontinued from the study and 
treated appropriately. If a participant endorses a 4 or 5 on the ideation subscale or any 
behavioral item of the C-SSRS on 2 occasions and is confirmed to have active SIB on both 
occasions by a risk assessment conducted by a qualified MHP, then the participant must be 
discontinued from the study and treated appropriately.
8.2.9.1. Columbia Suicide Severity Rating Scale
The C-SSRS is a validated tool for investigative staff to use to evaluate suicidal ideation and 
behavior.25 Trained site staff is to administer the C-SSRS to all participants at 
Screening/Baseline visits and assess the participant’s eligibility based on the answers. The C-
SSRS will also be administered at post-baseline visits to determine whether it is safe for the 
participant to continue in the trial. Refer to Section 8.2.9 for information on using this tool in 
SIB risk monitoring. When there is a positive response to any question on the C-SSRS, the 
investigator should determine whether an adverse event has occurred.
8.2.9.2. Patient Health Questionnaire – 8 Items (PHQ-8)
The PHQ-8 is a participant-reported questionnaire consisting of 8 items to assess the 
participant’s depression level.27 Site staff is to administer the PHQ-8 to all participants at 
screening and score immediately. Refer to Section 8.2.9 for information on using this tool in 
SIB risk monitoring.


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8.2.10. Pregnancy Testing 
For all WOCBP, a serum pregnancy test with a sensitivity of at least 25 mIU/mL will be 
performed at Screening. A urine pregnancy test will be performed at various time points 
described in the Schedule of Activities to confirm the participant has not become pregnant 
during the study. Serum and urine pregnancy test kits will be provided by the central 
laboratory with sample collection instructions provided in the package insert.
A negative pregnancy test result is required at the Baseline visit before the participant may 
receive the study intervention. Pregnancy tests will also be done whenever 1 menstrual cycle 
is missed (or when potential pregnancy is otherwise suspected). Pregnancy tests may also be 
repeated if requested by institutional review boards (IRBs)/ethics committees (ECs) or if 
required by local regulations.
Participants who have missed a menstrual period or who show an indeterminate or positive 
result on the urine test may not progress further in the study until pregnancy is ruled out 
using further diagnostic testing (eg, a negative quantitative serum pregnancy test conducted 
at a certified laboratory with a sensitivity of at least 25 mIU/mL).
In the case of a positive confirmed pregnancy, the participant will be withdrawn from 
administration of the study intervention but may remain in the study.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 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 it 
meets the criteria for classification as an SAE, or that caused the participant to discontinue 
the study intervention (see Section 7.1).
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.


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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.
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.2,3 Key cytokines implicated in the 
pathophysiology of AD include IL-4, IL-5, IL-13, IL-31, and IFN-. This is a randomized, 
double-blind, placebo-controlled, parallel-group, Phase 2a study to investigate the 
mechanism of action of abrocitinib by correlating efficacy outcomes with changes from 
baseline in key skin and blood biomarkers in adult participants 18 years of age with 
moderate-to-severe AD. 
Investigators are not obligated to actively seek AE or SAE 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 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 
Appendix 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 Appendix 3.


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Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading 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 Appendix 3.
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, IRB/ECs, and 
investigators.

Investigator safety reports must be prepared for 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/EC, 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.


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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 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
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 


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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 
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 


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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
Not applicable.
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
Not applicable.
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 participating participant.


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
Refer to Section 6.4 for examples of medication errors related to compliance with 
study intervention.
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.
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 nonserious, are recorded on the 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 study intervention greater than 8 tablets within a 24-hour time 
period [+/- 2 hours] will be considered an overdose. 
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the Medical Monitor immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
study intervention can no longer be detected systemically (at least 3 days).
3. Obtain a plasma sample for PK analysis within 28 days from the date of the last dose 
of study intervention if requested by the Medical Monitor (determined on a case-by-
case basis).
4. Document the quantity of the excess dose, as well as the duration of the overdose, in 
the CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Pfizer clinician based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
During the study, blood samples (8 mL) to provide approximately 4 mL of plasma for PK 
analysis will be collected into appropriately labeled tubes containing dipotassium 
ethylenediaminetetraacetic acid (K2-EDTA) for measurement of plasma concentration of 
abrocitinib and its metabolites PF-06471658, PF-07055087, and PF-07054874 at times 
specified in the Schedule of Activities. The actual date and time (24-hour clock time) of each 
sample will be recorded.


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Blood for PK analysis will be collected at the study site at the following time points:
•
Prior to dosing at Week 4; 
•
At 0.5 hours (±15 min) postdose at Week 4; 
•
At 0.5 hours (±15 min) postdose at Week 12;
•
At 4.0 hours (±30 min) postdose at Week 12. 
The actual times may change, but the number of samples will remain the same. All efforts
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of
samples up to and including 10 hours after dose administration that are obtained within 10% 
of the nominal time (eg, within 6 minutes of a 60-minute sample) relative to dosing will not 
be captured as a protocol deviation, as long as the exact time of the collection is noted on the 
source document and data collection tool (eg, CRF/DCT). Collection of samples more than 
10 hours after dose administration that are obtained ≤1 hour away from the nominal time 
relative to dosing will not be captured as a protocol deviation, as long as the exact time of the 
collection is noted on the source document and data collection tool (eg, CRF/DCT).
•
The plasma will be stored in appropriately labeled screw-capped polypropylene tube at 
approximately -80°C within 1 hour of collection.
•
Further details regarding the collection, processing, storage and shipping of the blood 
samples will be provided in the lab manual.
•
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures. 
•
The PK samples must be processed and shipped as indicated to maintain sample integrity. 
Any deviations from the PK processing steps, including any actions taken, must be 
documented and reported to the sponsor. On a case-by-case basis, the Sponsor may make 
a determination as to whether sample integrity has been compromised. Any sample 
deemed outside of established stability, or of questionable integrity, will be considered a 
protocol deviation.
•
 
8.5.1. Shipment of Pharmacokinetic Samples
The central laboratory will provide collection materials and directions for packaging and 
shipment of samples and will manage shipment of samples to the contract analytical 
laboratory.
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8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.7.2. Banked Biospecimens for Genetics
A 4 mL blood sample optimized for DNA isolation Prep D1 will be collected as local 
regulations and IRBs/IECs allow.
Banked Biospecimens may be used for research related to drug response and moderate to 
severe atopic dermatitis. Genes and other analytes (eg, proteins, RNA, non-drug metabolites) 
may be studied using the banked samples. 
Unless prohibited by local regulations or IRB/EC decision, participants will be asked to 
indicate on the consent form whether they will allow their Banked Biospecimen(s) to also be 
used to design and conduct research in order to gain a further understanding of other diseases 
and to advance science, including development of other medicines for patients. This 
component of the sample banking is optional for participants; they may still participate in the 
study even if they do not agree to the additional research on their Banked Biospecimens. The 
optional additional research does not require the collection of any further samples.
See Appendix 5 for Information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in the laboratory 
manual.
8.8. Biomarkers
, the following 
biomarkers will be evaluated in this study.
The following genes are considered key biomarkers associated with AD pathways: 
•
General inflammation (MMP12); 
•
Hyperplasia (K16); 
•
Th2 (CCL17, CCL18, CCL26); 
•
Th22 (S100A8, S100A9, S100A12).
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In addition, the following genes are considered:
Parameters studied using IHC will include epidermal thickness (performed on H&E 
sections), Ki-67+ cells, Keratin 16 (K16),
 
 
Gene expression by TLDA RT-PCR will include the levels of the following established 
cytokines associated with AD: 
 
 
S100A7, S100A8, S100A9, S100A12, MMP12, 
 
CCL18, 
 CCL26, 
 
18S and RPLP0 as control genes. 
Blood for analyses of changes in inflammatory and cardiovascular markers will be collected 
at Weeks 0, 2, 4, and 12. 
 
 
8.8.1. Specified Gene Expression Ribonucleic Acid (RNA) Research
Specified gene expression (RNA) research is included in this study and described in 
Section 8.8. 
8.8.2. Banked Biospecimens for Biomarkers
One 4 mL blood sample to provide serum (Prep B2.5) and a 3 mL blood sample to provide 
plasma (Prep B1.5) will be collected for each of the time points as per Schedule of Activities, 
as local regulations and IRB/ECs allow. 
Banked biospecimens may be used for research related to drug response and moderate to 
severe atopic dermatitis. Genes and other analytes (eg, proteins, RNA, nondrug metabolites) 
may be studied using the banked samples. 
Unless prohibited by local regulations or IRB/EC decision, participants will be asked to 
indicate on the consent document whether they will allow their banked samples to also be 
used to design and conduct research in order to gain a further understanding of other diseases 
and to advance science, including development of other medicines for patients. This 
CCI
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component of the sampling banking is optional for participants; they may still participate in 
the study even if they do not agree to the additional research on their banked samples. The 
optional additional research does not require the collection of any further samples.
See Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the central lab manual.
8.9. Health Economics OR Medical Resource Utilization and Health Economics
Not applicable to the study.


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9. STATISTICAL CONSIDERATIONS
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The primary objective of this study is to assess the effects of abrocitinib on lesional and non-
lesional skin biomarkers of adult participants with moderate-to-severe AD. The following 
estimand attributes will be considered:

Population: Participants with moderate-to-severe AD as defined by the inclusion 
criteria;

Variable: Fold-change from baseline in the biomarkers for general inflammation 
(MMP12), hyperplasia (K16), Th2 immune response (CCL17, CCL18, CCL26), and 
Th22 immune response (S100A8, S100A9, S100A12);

Intercurrent event: All data collected will be utilized;

Participants need to have a baseline and week 12 assessment to be included in the 
analysis.

Population-level summary: Mean fold-change from baseline within each treatment 
group.
9.2. Sample Size Determination
The sample size of this study is based on the objective to evaluate changes in key AD 
biomarkers in skin lesions, including biomarkers for general inflammation (MMP12), 
hyperplasia (K16), Th2 (CCL17, CCL18, CCL26), and Th22 (S100A8, S100A9, S100A12) 
with abrocitinib 200 mg QD, abrocitinib 100 mg QD, and placebo.
A total sample of approximately 51 participants, with 17 participants randomized to 
abrocitinib 200 mg QD, 17 participants randomized to abrocitinib 100 mg QD, 
17 participants randomized to matching placebo (1:1:1 randomization) is planned.
A sample size of 17 participants per treatment group would provide about 92% chance that 
the 95% CI for the mean fold-change (post-baseline relative to baseline) has a half-width of 
no more than 3.2 (which is within 64% of an assumed maximal standard deviation of 5 for 
the fold-change, as based on published data). 28 Calculations are based on the assumption of a 
chi-square distribution for the estimated sample variance so that the width of the estimated 
confidence interval is a random quantity.


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9.3. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Full Analysis Set (FAS)
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Participants will 
be analyzed according to the intervention they are randomized 
to. 
Per Protocol Analysis Set 
(PPAS)
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Furthermore, 
participants must not have any major protocol violations such 
inclusion/exclusion criteria, inadequate protocol compliance in 
terms of dosing or study activities or any other major protocol 
violation as determined by the clinical study team prior to 
unblinding. Participants will be analyzed according to the 
intervention they are randomized to.
Safety Analysis Set 
(SAS)
All participants who take at least 1 dose of study intervention. 
Participants will be analyzed according to the intervention 
they actually received. 
9.4. Statistical Analyses
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor. The SAP may modify what is outlined in the protocol where 
appropriate.
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, for all endpoints listed in Section 3, 
and procedures for accounting for missing data. This section is a summary of the planned 
statistical analyses of the primary and secondary endpoints.
9.4.1. Analysis of the Primary Endpoint
The population for the primary analysis will be all participants in the FAS having valid 
biomarker data at baseline and Week 12. 
The primary endpoints in this study include mean fold-changes for the following biomarkers: 

General inflammation (MMP12); 

Hyperplasia (K16); 


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
Th2 (CCL17, CCL18, CCL26); 

Th22 (S100A8, S100A9, S100A12).
In each participant, expression levels from RT-PCR will be normalized to the housekeeping 
gene RPLP0 (validated in other studies) by negatively transforming the Ct values to –dCt, 
obtaining an equivalent to log2 scale expression values (reporting unit: log2 
[Expression/RPLP0]). The expression values below detection will be estimated for each gene 
as the 20% of the minimum of unlogged values across all samples (which is equivalent to 
subtracting 2.321928 from the –dCt minimum value). The expression levels below detection 
may provide important information about some markers that significantly change with 
treatment (eg, the expression may decrease below the level of detection after treatment), 
therefore this imputation is an important step in the analysis. 
RT-PCR expression data in log2 scale will be modeled using a mixed effect model with 
Treatment, Time Point, and Tissue Type as a fixed effect and a random intercept for each 
participant. This model will yield unbiased estimates and valid inferences in the presence of a 
missing data mechanism that is missing at random (MAR). 29 This approach introduces less 
bias than restricting the analysis for participants with complete observations and is consistent 
with estimation of a hypothetical estimand. Contrasts will be used to estimate the log2 fold-
changes for each treatment group. Fold-changes will be computed by obtaining the antilog of 
log2 fold-changes. Point estimates and 95% confidence intervals (CIs) will be obtained for 
the fold-change from baseline in the biomarker values for each treatment group based on this 
model.
Correlation analyses will be performed to assess if the fold-change from baseline in 
biomarkers correlates with change (from baseline) in the clinical efficacy endpoints such as 
IGA, EASI, and Peak Pruritus NRS.
Supportive analyses for the primary endpoint will also be performed using the PPAS. 
While statistical tests of hypotheses will not be performed to compare the fold-change from 
baseline in the abrocitinib groups versus placebo, the point estimates and 95% CIs for the 
two abrocitinib dose groups will be assessed in relation to those from the placebo group. A 
fold-change from baseline observed in the abrocitinib groups alone (and correlated with 
efficacy) but not in the placebo group is likely due to the mechanism of action of abrocitinib.


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9.4.2. Analysis of Other Biomarker Endpoints
 
Parameters studied using IHC will include epidermal thickness (performed on H&E 
sections), Ki-67+ cells, Keratin 16 (K16),
 
.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gene expression by TLDA RT-PCR will include the levels of the following established 
cytokines associated with AD: 
 
 
100A7, S100A8, S100A9, S100A12, MMP12, 
 
, CCL18, 
, CCL26, 
 
 18S and RPLP0 as control genes. 
 
 
 
 
 
CCI
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CCI
CCI
CCI
CCI
CCI
CCI
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9.4.2.1. Analysis of Other Endpoints
The responses based on IGA, EASI (eg, EASI-75), and severity scale of the Peak Pruritus 
NRS will be summarized descriptively by visit and treatment. The difference of the 
improvement from baseline between each abrocitinib dose and placebo will also be derived.
If a participant withdraws from the study, then this participant will be considered a 
non-responder after withdrawal for any binary valued clinical efficacy endpoint.
9.4.3. Safety Analyses
All safety analyses will be performed on the Safety Population. The Safety population will 
include any participant receiving ≥1 dose of investigational product.
All safety data will be summarized using descriptive statistics. No imputation will be made 
for missing safety data.
All safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, categorical summaries, and graphical presentations. Safety endpoints 
for the study include:
•
Treatment-emergent AEs and SAEs;
•
Withdrawals from active treatment due to AEs;
•
Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
hospitalization or parenteral antimicrobials or met other criteria that required the 
event be classified as serious;
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•
Safety laboratory tests (eg, hematology [including coagulation panel], chemistry, and 
lipid profiles);
•
Vital signs;
•
ECG parameters if applicable.
 
9.5. Interim Analyses
After the first 15 participants have completed the study, there will be an interim analysis to 
examine platelet values. A longitudinal analysis will be conducted to determine if there is a 
change from baseline in platelet values. The data will remain blinded so that no one will 
know the participants’ assigned treatment and thus the analysis will not analyse for any 
treatment differences. Correlation analyses may also be conducted to look for potential 
relationships between platelet values 
. There will 
not be any decision rules associated with this interim analysis, so there will be no changes to 
the conduct or continuation of the trial based on these analyses.
9.5.1. Data Monitoring Committee (DMC)
This study will use an E-DMC. The E-DMC is independent of the study team and includes 
only external members. The E-DMC will be responsible for ongoing monitoring of the safety 
of participants in the study according to the charter. 
The recommendations made by the E-DMC to alter the conduct of the study will be 
forwarded to Pfizer for final decision. Pfizer will forward such decisions, which may include 
summaries of aggregate analyses of endpoint events and of safety data that are not endpoints, 
to regulatory authorities, as appropriate. Composition of the E-DMC and processes under 
which the E-DMC operates will be documented in the E-DMC charter.
CCI
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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, ICF, Investigator Brochure, 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 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and all 
other applicable local regulations

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.
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 


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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 or his/her legally authorized representative (parent(s)/legal guardian) and 
answer all questions regarding the study.

Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of 
informed consent/assent 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 or his or her legally 
authorized representative 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 or his or her legally 
authorized representative 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/assent 
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 ICF.

Participants must be re-consented to the most current version of the ICF(s) and if the 
age of majority is reached during their participation in the study.

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.


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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
External Data Monitoring Committee (E-DMC)
See Section 9.5.1.
Safety Adjudication Committees
To help assess the specific, complex safety events related to malignancies, cardiovascular 
events, hepatic and opportunistic infection (including eczema herpeticum and other 
infections of special interest) in this study, Safety Adjudication Committees, consisting of 
clinical experts in each of the relevant clinical areas, will be set up to harmonize and 
standardize assessments. In order to allow for an unbiased safety assessment, the members of 
these committees will be blinded to treatment assignment. Further information about the 
Safety Adjudication Committees can be found in their respective charters, including a 
specific description of the scope of their responsibilities, a plan where communication 
timelines are defined, and the exact process and definitions used by each committee to 
adjudicate the safety events that they will adjudicate. Other safety events for adjudication 
may be identified and included in the remit of the Safety Adjudication Committees as 
appropriate.


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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 US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted. US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements. EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (Clinical Study Report [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 US Basic 
Results document is posted to www.clinicaltrials.gov.
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 


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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 
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 


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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 ICFs, 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.

Definition of what constitutes source data can be found in the Clinical Monitoring 
Plan.
10.1.9. Study and Site Closure
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.


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The investigator may initiate study-site closure at any time upon notification to contract 
research organization (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
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 
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.


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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 clinical trial management system. 
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 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 the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 7 will be performed by the central laboratory.

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 such 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. This is applicable for repeat 
tests.

Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in section 5 of the protocol.

Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations.

Pregnancy Testing 
1. Refer to Section 5.1 Inclusion Criteria and Section 8.2.10 Pregnancy Testing 
for screening pregnancy criteria.
2. For details of timing of recommended pregnancy testing see the Schedule of 
Activities.


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Table 7.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
 
Hemoglobin
Hematocrit
RBC Indices:
MCV
MCH
MCHC
RBC Morphology
Reticulocyte Count 
White blood cell (WBC) 
count with Differential:
Total Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Coagulation Panel
Activated Partial 
Thromboplastin Time 
(APTT) 
Prothrombin 
Time/International 
Normalized Ratio 
(PT/INR)
Clinical 
Chemistry1
Blood urea nitrogen 
(BUN) 
Creatinine 
Creatine 
Phosphokinase
Glucose (non-
fasting) (Day 1 and 
Week 12 fasting)
AST
ALT 
GGT
Potassium 
Sodium
Calcium
Chloride
Uric acid
Albumin
Total Protein
Total CO2 
(bicarbonate)
Total, indirect and 
direct bilirubin
Alkaline 
phosphatase
Lactate 
dehydrogenase 
Lipid Profile 
Panel1
Total cholesterol
Triglycerides
LDL 
HDL
Routine 
Urinalysis
•
pH, glucose, protein, blood, ketones, nitrite, leukocyte esterase by dipstick
•
Microscopic examination and/or culture2
Other Tests9
•
HIV3
•
HBsAg3
•
HBcAb3
•
HBsAb3,4
•
HBV DNA5
•
HCVAb3,4
•
HCV RNA3,4
•
Viral test at baseline
•
Serum Pregnancy Test3,6
•
Urine pregnancy test6
•
QFT-G or PPD (if applicable)7
•
•
Lymphocyte Subsets 
Total T cells (CD3+)
CD4+ T cells (CD3+CD4+)
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Table 7.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
CD8+ T cells (CD3+CD8+)
NK cells (CD3-CD16+CD56+)
B cells (CD3-CD19+)
1.
Lipid profile panel requires at least an 8 hour fast. Lipid profile panel will be completed at Day 1 and 
Week 12, and will include total cholesterol, LDL, HDL, and triglycerides. 
2.
Microscopy performed at all visits and culture as appropriate.
3.
At Screening only. HIV testing will be performed for all participants.
4.
HBsAb reflex testing only if HBsAg negative but HBcAb positive. HCV RNA is reflex testing only if 
HCVAb is positive.
5.
Participants who are HBsAg negative, HBcAb positive, and HBsAb positive will have reflex testing for 
HBV DNA. 
6.
Pregnancy testing for all WOCBP.
7.
PPD results should be read within 48 to 72 hours.
9.
All study-required laboratory assessments will be performed by a central laboratory, with the exception 
of: urine pregnancy tests, which will be performed on the Day of the study visits per the Schedule of 
Activities.
Investigators must document their review of each laboratory safety report.
Laboratory results that could unblind the study will not be reported to investigative sites or 
other blinded personnel until the study has been unblinded.
C
C


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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 sign 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 preexisting 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.
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as an AE or SAE if they fulfill the definition of an AE or SAE and meet the 


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requirements as per Section 8.3.8.1. Also, “lack of efficacy” or “failure of expected 
pharmacological action” does not constitute an AE or SAE.
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).
An 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.


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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, 
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/Reporting 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 CT 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 


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terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information
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 CT SAE Report 
Form/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 
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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 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. 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.


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Follow-up of AEs and SAEs

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 healthcare providers.

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 the data 
become 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 CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.


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
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form 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)
For this study, a female participant is considered fertile (ie WOCBP) starting at 12 years of 
age (regardless of whether they have experienced/reported menarche) unless permanently 
sterile (see below).
Women with one of the following are not considered WOCBP

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, Müllerian 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.
Contraception Guidance:
All female participants who are considered WOCBP and who are, in the opinion of the 
investigator, sexually active and at risk for pregnancy with their partner(s) must agree to use 
a highly effective method of contraception consistently and correctly for the duration of the 
active treatment period and for at least 28 days after the last dose of study intervention. The 
investigator or his or her designee, in consultation with the participant, will confirm that the 
participant has selected an appropriate method of contraception for the individual participant 
and her partner from the permitted list of contraception methods (see below) and will confirm 
that the participant has been instructed in its consistent and correct use. At time points 
indicated in the Schedule of Activities, the investigator or designee will inform the 
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 or if 
pregnancy is known or suspected in the participant. 


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Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal) provided the 
participant plans to remain on the same treatment throughout the entire study and has 
been using that hormonal contraceptive for an adequate period of time to ensure 
effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD). 
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the participant.
The contraception check is an opportunity to confirm that contraception, if assigned, is used 
consistently and correctly. It also facilitates continual reassessment of child-bearing potential 
in women. This allows for implementing necessary changes to contraception; for example, 
investigators may need to ensure alternative contraceptive methods if new concomitant 
disease contraindicates a selected method of contraception, or if a participant is demonstrably 
no longer of child-bearing status (as per protocol) then they will no longer require 
contraception. Continual reassessment of contraceptive needs is imperative.
Collection of Pregnancy Information:
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the study 
intervention; or the female becomes or is found to be pregnant after discontinuing 
and/or being exposed to the study intervention;

An example of environmental exposure would be a case involving direct 
contact with a Pfizer product in a pregnant woman (eg, a nurse reports that she 
is pregnant and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to 
the study intervention prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy. 
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the study intervention, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, 
regardless of whether an SAE has occurred. In addition, the investigator must submit 


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information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form. This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure. The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless pre-
procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as SAEs. In addition, infant deaths after 1 month should be 
reported as SAEs when the investigator assesses the infant death as related or 
possibly related to exposure to the 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 the participant 
was given the Pregnant Partner Release of Information Form to provide to his partner.


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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRB/IEC allow, a blood sample will be collected for DNA analysis.

Genetic research may consist of the analysis of one or more candidate genes or the 
analysis of genetic markers throughout the genome or analysis of the entire genome 
(as appropriate).

The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to abrocitinib or study interventions of this class, 
treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in the clinical study report (CSR) or 
in a separate study summary, or may be used for internal decision-making without 
being included in a study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.

The samples will be retained as indicated:

Samples for banking (see Section 8.7.2 and 8.8.2) will be stored 
indefinitely or other period as per local requirements.

Participants may withdraw their consent for the storage and/or use of their Banked 
Biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed. Data already generated from the samples will 
be retained to protect the integrity of existing analyses.
Banked Biospecimens will be labelled with a code. The key between the code and the 
participant’s personally identifying information (eg name, address) will be held at the study 
site and will not be provided to the sample bank. 


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
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:
o
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;
o
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:

Preexisting AST or ALT baseline values above the normal range: AST or 
ALT values >2 times the baseline values AND >3 × ULN; or >8 × ULN 
(whichever is smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × 
ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the Sponsor. The participant 
should return to the investigator site and be evaluated as soon as possible, preferably within 


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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 liver function test (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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10.7. Appendix 7: Prohibited Concomitant Medications
CYP2C19 Inhibitors 
CYP2C19 Inducers
Fluconazole (Diflucan)
Enzalutamide (Xtandi)
Fluvoxamine (Luvox)
Rifampin
Ticlopidine (Ticlid)
Esomeprazole (Nexium)
Fluoxetine (Prozac)
Moclobemide
Omeprazole (Prilosec)
Voriconazole (Vfend)
CYP2C9 Inhibitors 
CYP2C9 Inducers
Fluconazole (Diflucan)
Carbamazepine (Tegretol)
Amiodarone (Cordarone)
Enzalutamide (Xtandi)
Fluvoxamine (Luvox)
Rifampin
Miconazole
Oxandrolone (Oxandrin)
Voriconazole (Vfend)
Note 1: All CYP2C9 and CYP2C19 inhibitors require at least 1 week or at least 5 half-lives 
(whichever is longer) washout period prior to the first dose of study intervention.
Note 2: All CYP2C9 and CYP2C19 inducers require a period of washout of at least 
5 half-lives plus 14 days prior to the first dose of study intervention. For example, the 
average half-life of carbamazepine after repeat dosing is 15 hours. The washout period is 
calculated as the sum of 5 half-lives (approximately 3 days) and an additional 14 days for a 
total of 17 days prior to the first dose of study intervention.
Note 3: Half-life refers to the half-life of the parent drug and its metabolites, which are 
inhibitors or inducers. The longest half-life should be used to calculate the period necessary 
to washout a medication prior to the first dose of study intervention. For example, fluoxetine 
and its metabolite norfluoxetine are both inhibitors of CYP2C19. The terminal half-life of 
fluoxetine is up to 6 days. However, norfluoxetine has a longer half-life, up to 16 days. 
Therefore, the washout period should be calculated based on the 5 times the half-life of 
norfluoxetine (approximately 80 days) and an additional 14 days for a total of 94 days prior 
to the first dose of study intervention.
This is not an all-inclusive list. Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that are CYP2C9 or CYP2C19 inhibitors 
or inducers.


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10.8. Appendix 8: Country-specific Requirements
Not applicable.


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10.9. Appendix 9: Abbreviations
AD
atopic dermatitis
AE
adverse event
ALT
alanine aminotransferase
AMR
Ashwell-Morrell receptor
APTT
activated partial thromboplastin time
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
Area under the curve
AUCinf
area under the plasma concentration-time profile from time zero
extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time zero 
to the time of the last quantifiable concentration
AUCtau
area under the curve over dosing interval tau
BCG
Bacille Calmette Guérin
BID
twice a day
BSA
body surface area
BUN
blood urea nitrogen
CCL
C-C motif chemokine ligand
CD
cluster of differentiation
CFB
Change from baseline
CFP-10
Cell filtrate protein 10
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CL/F
clearance/fraction of dose absorbed
Cmax
maximum plasma concentration 
CO2
carbon dioxide
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
corona virus disease 2019
CK
creatine kinase
CRF
case report form
CRO
contract research organization
CsA
cyclosporine A
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
CTLA3
Cytotoxic T-lymphocyte associated protein 3
CV
coefficient of variation
DC
dendritic cell
DCT
data collection tool
DEFB4
defensin beta 4A
CCI


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DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EASI
Eczema Area and Severity Index
EBV
Epstein Barr virus
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
ELISA
Enzyme-Linked Immunosorbent Assay
EMA
European Medicines Agency
EOS
end of study
EOT
end of treatment
EPO
erythropoietin
ESAT-6
Early secretory antigen 6
ET
early termination 
EU
European Union
EudraCT
European Clinical Trials Database
FACS
fluorescence-activated cell sorting
FAS
full analysis set
FDA
Food and Drug Administration 
FLG
filaggrin
FOXP3
forkhead box P3
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBcAb 
hepatitis B core antibody
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb 
hepatitis C viral antibody
HCV RNA
hepatitis C viral ribonucleic acid
HDL
high-density lipoprotein 
H&E
hematoxylin and eosin
HEENT
head, eyes, ears, nose and throat
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HSV
herpes simplex virus
HTA
health technologies assessment 
CCI
CCI


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IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council on Harmonisation
ID
identification
IEC
Independent Ethics Committees
IFN
interferon
IFN-
interferon-alpha
IFN-
interferon-gamma
IGA
Investigator’s Global Assessment
IgE 
Immunoglobulin E
IgG
immunoglobulin G
IHC
immunohistochemistry
IIV
inter individual variability
IL
interleukin
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IWR
interactive web response
JADE
Jak1 Atopic Dermatitis Efficacy and safety program
JAK1
Janus kinase 1
K16
Keratin 16
K2EDTA
dipotassium ethylenediaminetetraacetic acid
LCN2
lipocalin 2
LDL
low-density lipoprotein
LFT
liver function test
LLQ
lower limit of quantification
LMW
low molecular weight
LS
lesional
LSLV
last subject last visit 
LTE
long-term extension
MAR
missing at random
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MHP
mental health professional
MMP
matrix metallopeptidase
MNAR
missing not at random
MOA
mechanism of action
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
MX1
MX dynamin like GTPase 1


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N/A
not applicable
NB-UVB
narrowband ultraviolet B light
NL
non-lesional
NRS
numerical rating scale
NRS4
numerical rating scale 4 points improvement from baseline
NRS 
numerical rating scale
NSAID
nonsteroidal anti-inflammatory drug
OASL
2'-5'-oligoadenylate synthetase like
OTC
over-the-counter
PCA
Principal Component Analysis
PCD
primary completion date
PCP
primary care physician
PCR
polymerase chain reaction
PDL1
programmed cell death ligand 1
PEER
Pediatric Eczema Elective Registry
PGx
Pharmacogenomics
PI3
Peptidase inhibitor 3
PK
Pharmacokinetics
POC
proof of concept
PPAS
per protocol analysis set
PPD
purified protein derivative
PP-NRS
peak pruritus numerical rating scale
PRO
patient reported outcome
PT
prothrombin time
QC
quality control
QD
once daily
QFT-G
QuantiFERON®-TB Gold
QT
Q wave interval
QTc
corrected Q wave interval
QTcF
Fridericia corrected Q wave interval
qRT-PCR
quantitative reverse transcriptase polymerase chain reaction
Rac
accumulation ratio 
RBC
red blood cell
RNA
ribonucleic acid
RPLP0
Ribosomal protein lateral stalk subunit P0
RT-PCR
reverse transcriptase polymerase chain reaction
S100A
S100 calcium binding protein A
SAE
serious adverse event
SAP
statistical analysis plan
SAS
safety analysis set
SOC
system organ class
SOP
standard operating procedure
SRSD
single reference safety document
STAT
signal transducers and activators of transcription


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SUSAR
suspected unexpected serious adverse reaction
t½
half-life
Tmax
time to maximum absorption
TB
tuberculosis
TBili
total bilirubin
TCI
topical calcineurin inhibitors
TCS
topical corticosteroids
Th2
type 2 helper T cell
Th22
type 22 helper T cell
TLDA
Taqman Low Density Array
TPO
thrombopoietin
TSLP
thymic stromal lymphopoietin
TSLPR
thymic stromal lymphopoietin receptor
TYK2
tyrosine kinase 2
ULN
upper limit of normal
US
United States
UV
ultraviolet
UVA
ultraviolet A light
UVB
ultraviolet B light
VAS
visual analog scale
V/F
volume of distribution/fraction absorbed
WBC
white blood cell
WOCBP
women of childbearing potential


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10.10. Appendix 10: Monitoring and Discontinuation Criteria
Monitoring Criteria 
The following laboratory abnormalities require prompt retesting:

Neutrophil counts <1000 neutrophils/mm3; confirmed promptly by repeat testing, 
ideally within 3-5 days; 

Platelet counts <75,000 platelets/mm3; confirmed promptly by repeat testing, ideally 
within 3-5 days; 

Any single hemoglobin value <9.0 g/dL or one that drops 2 g/dL below baseline; 
confirmed promptly by repeat testing, ideally within 3-5 days; 

Any single AST and/or ALT elevation >3 times the upper limit of normal regardless 
of accompanying symptoms or the total bilirubin should prompt repeat testing. This 
should also prompt review of Appendix 6 (Liver Safety); additional investigations 
must be conducted.
Temporary Interruption to Dosing
Temporary interruption to dosing is not allowed in this study, except when specified in the 
protocol for participant safety.
Discontinuation Criteria
Participants must be permanently discontinued from treatment if they meet any of the 
following criteria at any point in the study:

Marked prolongation of the QTcF interval to >500 ms or >60 ms change from 
screening ECG. 

Serious infection (see definition for Serious Adverse Events in Section 10.3.2) must 
result in temporary interruption of study intervention. Study intervention cannot be 
restarted until the serious infection has resolved, and this has been discussed and 
agreed with the Pfizer medical monitor. If the participant cannot be restarted on study 
intervention within 21 days, or the infection is not resolved, or there is no agreement 
received from the Pfizer medical monitor to restart study intervention then the 
participant must be permanently discontinued from study intervention. 

Any bleeding event thought to be associated with a platelet count reduction per the 
judgement of the investigator (or, if necessary/desired, following discussion with 
sponsor).

Adverse event, per judgment of the investigator, requiring discontinuation from 
treatment (or, if necessary/desired, following discussion with sponsor).


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NOTE: any initial lab value below must be retested within 48 hours.

Two sequential platelet counts <50,000/mm3. If the participant has a platelet count 
<25,000/mm3, study intervention should be temporarily withheld pending the 
confirmatory retest.

Two sequential neutrophil counts <500/mm3.

Two sequential lymphocyte counts <500/mm3.

Two sequential hemoglobin assessments <8.0 g/dL and / or a decrease of >30% from 
baseline value.

Any of the following:

Two sequential AST or ALT elevations >3 times the upper limit of normal with at 
least one total bilirubin value >2 times the upper limit of normal.

Two sequential AST or ALT elevations >3 times the upper limit of normal with 
an abnormal international normalized ratio (INR).

Two sequential AST or ALT elevations >3 times the upper limit of normal 
accompanied by symptoms consistent with hepatic injury.

Two sequential AST or ALT elevations >5 times the upper limit of normal, 
regardless of total bilirubin or accompanying symptoms.
NOTE: Any of the above findings should prompt review of “The Potential Cases of 
Drug-Induced Liver Injury,” Appendix 6 for which additional investigations must be 
conducted.

Two sequential increases in serum creatinine that are >50% over the average of 
screening and baseline values AND an absolute increase in serum creatinine 
0.5 mg/dL. At the time of study completion or discontinuation, if a participant 
should exhibit elevations in serum creatinine 33% above the average of screening 
and baseline values, they will be re-tested every 1 to 2 weeks until the serum 
creatinine elevation is fully reversed to within 10% of the average of screening and 
baseline values or has stabilized.
Having met Discontinuation Criteria, the participant must be permanently withdrawn from 
treatment, have their end of treatment visit, and will then enter the 4-week follow-up period. 
Additional individual participant safety monitoring, including laboratory testing or 
unscheduled study visits, in addition to these guidelines is at the discretion of the investigator 
and dependent on any perceived safety concerns. Unscheduled laboratory testing through the 
central laboratory may be obtained at any time during the study to assess such concerns. 


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If a participant has a clinically significant, treatment emergent, abnormality at the time of 
withdrawal from the study, the Pfizer clinician (or designee) should be notified and every 
effort should be made to arrange follow-up evaluations at appropriate intervals to document 
the course of the abnormality. All abnormal laboratory events of clinical significance should 
be followed until the laboratory values have returned to normal or baseline levels or are 
deemed clinically stable. Follow-up for abnormal laboratory findings and adverse events by 
the investigator is required until the event or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment.


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10.11. Appendix 11: Diagnostic Criteria for Atopic Dermatitis
Per Inclusion Criterion 2, a participant is to have a clinical diagnosis of AD according to the 
criteria of Hanifin and Rajka.20
Hanifin and Rajka’s Diagnostic Criteria for Atopic Dermatitis
Must have three or more basic features described below:
Pruritus
Typical morphology and distribution:
Flexural lichenification in adults
Facial and extensor eruptions in infants and children
Chronic or chronically-relapsing dermatitis
Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis)
Must have three or more following minor features:
Xerosis
Ichthyosis/palmar hyperlinearity, keratosis pilaris
Immediate (type 1) skin test reaction
Elevated serum IgE
Early age of onset
Tendency toward cutaneous infections (esp. staph. aureus and herpes simplex), impaired 
cell-mediated immunity
Tendency toward non-specific hand or foot dermatitis
Nipple eczema
Cheilitis
Recurrent conjunctivitis
Dennie-Morgan infraorbital fold
Keratoconus
Anterior subcapsular cataracts
Orbital darkening
Facial pallor, facial erythema
Pityriasis alba
Anterior neck folds
Itch when sweating
Intolerance to wool and lipid solvents
Periofollicular accentuation
Food intolerance
Course influenced by environmental and emotional factors
White dermographism, delayed blanch


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10.12. Appendix 12: Fitzpatrick Skin Type


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10.13. Appendix 13: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally or specific location(s) and will become effective for other 
public emergencies only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
10.13.1. Telehealth Visits
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. 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 (e.g., audio, video, video-
conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit: 

Review and record study intervention(s), including compliance and missed doses.

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method and results of pregnancy testing. Confirm that 
the participant is adhering to the contraception method(s) required in the protocol. Refer 
to Appendix 4 and Section 8.2.10 of this appendix regarding pregnancy tests.

Review Patient-Reported Outcomes (PROs) and C-SSRS.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
10.13.2. Alternative Facilities for Safety Assessments
10.13.2.1. Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local 
regulations. The local laboratory may be a standalone institution or within a hospital. All 
safety laboratory tests required per protocol could be done at local labs with an exception of 
hs-CRP test to avoid the risk of potential unblinding.
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/ 


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accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible.  The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should 
be recorded on the CRF. 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 mIU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. 
10.13.3. 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. 
10.13.4. Home Health Visits
A home health care visit may be performed to facilitate scheduled visits per the Schedule of 
Activities. 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. The 
following may be performed during a home health visit:

Review and record study intervention(s), including compliance and missed doses.

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Physical exam and targeted physical exam.

Clinical AD assessments.

Vital sign measurements.

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 8.2.10 of this appendix regarding pregnancy tests.


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•
Review Patient-Reported Outcomes (PROs) and C-SSRS.
•
Skin punch biopsy, 
 could be performed by 
qualified personnel at their discretion. 
10.13.5. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an adverse event 
(AE) or serious adverse events (SAE) and appropriate medical intervention provided. 
Temporary discontinuation of the study intervention may be medically appropriate until the 
participant has recovered from COVID-19. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
10.13.6. Efficacy Assessments
The IGA and EASI efficacy assessments may be assessed by a qualified rater as part of a 
home health care visit, but cannot be completed as part of a TeleHealth visit. 
PROs may be completed as part of a home health care visit or a TeleHeath visit.
10.13.7. Independent Oversight Committees
The Data Monitoring Committee will be informed of considerations during Public Health
Emergencies such as COVID-19 that may impact participant participation, participant safety,
or study operations.
CCI


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11. REFERENCES
1.
Suarez-Farinas M, Ungar B, Correa da Rosa J, et al. RNA sequencing atopic dermatitis 
transcriptome profiling provides insights into novel disease mechanisms with potential 
therapeutic implications. J Allergy Clin Immunol 2015;135:1218-27.
2.
Bieber T. Atopic dermatitis. N Engl J Med 2008;358:1483-94.
3.
Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic 
dermatitis and psoriasis—part I: clinical and pathologic concepts. J Allergy Clin 
Immunol 2011;127:1110-8.
4.
Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin 
skin expression. J Allergy Clin Immunol 2007;120:150-5.
5.
Sehra S, Yao Y, Howell MD, et al. IL-4 regulates skin homeostasis and the 
predisposition toward allergic skin inflammation. J Immunol 2010;184:3186-90.
6.
Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and 
immune dysregulation. Immunol Rev 2011;242:233-46.
7.
Auriemma M, Vianale G, Amerio P, et al. Cytokines and T cells in atopic dermatitis Eur 
Cytokine Netw 2013; 24(1):37-44.
8.
Grozovsky R, Giannini S, Falet H, Hoffmeister KM. Novel mechanisms of platelet 
clearance and thrombopoietin regulation. Curr Opin Hematol. 2015;22(5): 445–451.
9.
Eichenfield LF, Ellis CN, Mancini AJ, et al. Atopic dermatitis: epidemiology and 
pathogenesis update. Semin Cutan Med Surg 2012; 31(3 Suppl):S3-5.
10.
Leicht S, Hanggi M. Atopic dermatitis. How to incorporate advances in management. 
Postgrad Med 2001; 109(6):119-27.
11.
Margolis JS, Abuabara K, Bilker W, et al. Persistence of mild to moderate atopic 
dermatitis. JAMA Dermatol 2014; 150(6):593-600.
12.
Deckers I, McLean AS, Linssen S, Mommers M, et al. Investigating international time 
trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review 
of epidemiological studies PLoS One 2012;7(7):e39803.
13.
Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and 
other health and demographic factors: a US population-based study. J Allergy Clin 
Immunol 2013; 132(5): 1132-8.
14.
Homey B, Steinhoff M, Ruzicka T, et al. Cytokines and chemokines orchestrate atopic 
skin inflammation.J Allergy Clin Immunol 2006;118(1):178-89.


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15.
Slater NA, Morrell DS. Systemic therapy of childhood atopic dermatitis. Clin Dermatol 
2015; 33(3): 289-99.
16.
Leung DY, Bieber T. Atopic dermatitis. Lancet 2003; 361(9352):151-60.
17.
Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic eczema (atopic 
dermatitis) part I. J Eur Acad Dermatol Venereol 2012; 26(8):1045-60.
18.
Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in 
children and adults: European Academy of Allergology and Clinical 
Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL 
Consensus Report. J Allergy Clin Immunol 2006; 118:152-69.
19.
Weidinger S, Ring J. Chapter 9. Diagnosis of atopic eczema. In: Ring J, Przybilla B, 
Ruzicka T, editors. Handbook of atopic eczema. 2nd ed. New York: Springer-Verlag;
2005:p. 83-99.
20.
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 
1980; 92(suppl):44-7.
21.
Yosipovitch G, Reaney M, Mastey V, et al. Validation of the peak pruritus numerical 
rating scale: Results from clinical studies of dupilumab in adult patients with 
moderate-to-severe atopic dermatitis: 5063. Journal of the American Academy of 
Dermatology. 2017; 76(6):AB278.
22.
Simpson E, Beck L, Abhijit G, et al. Defining a responder on the Peak Pruritus 
Numerical Rating Scale (NRS) in patients with moderate-to-severe atopic dermatitis: 
detailed analysis from randomized trials of dupilumab. J Am Acad of Dermatol 2017; 
76:AB93.
23.
Ersser SJ, Cowdell F, Latter S, et al. Psychological and educational interventions for 
atopic eczema in children. The Cochrane Database Syst Rev 2014; (1): CD004054. 
24.
Schmitt J, Langan S, Williams H, et al. What are the best outcome measurements for 
atopic eczema? A systematic review. J Allergy Clinical Immunol 2007; 120(6):1389-98. 
25.
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 suicidal 
risk analysis of antidepressants. Am J Psychiatry 2007; 164(7):1035-43.
 
27.
Kroenke K, Strine T, Spitzer C, et al. The PHQ 8 as a measure of current depression in 
the general population 2009. J Affect Disord 2009;114(13):163–73.
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CI


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28.
Hamilton JD, Suarez-Farinas M, Dhingra N, et al. Dupilumab improves the molecular 
signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin 
Immunol. 2014;134(6):1293-1300.
29.
R Core Team (2018). R: A language and environment for statistical computing. R 
Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-
project.org/. 

SAP_005.pdf: 
Protocol B7451037 (PF-04965842) Statistical Analysis Plan 
 
 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
 
PROTOCOL B7451037 
 
 
A PHASE 2A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL GROUP, MULTI-CENTER STUDY TO INVESTIGATE THE 
MECHANISM OF ACTION OF PF-04965842 MONOTHERAPY IN ADULT 
PARTICIPANTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS 
 
 
 
STATISTICAL ANALYSIS PLAN  
(SAP) 
 
 
Version: 
3 
Date:  
8 SEP 2021 
 
 


Protocol B7451037 (PF-04965842) Statistical Analysis Plan 
 
 
PFIZER CONFIDENTIAL 
Page 2 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ...........................................................................................................2 
LIST OF TABLES .....................................................................................................................4 
LIST OF FIGURES ...................................................................................................................4 
APPENDICES ...........................................................................................................................4 
1. VERSION HISTORY ............................................................................................................5 
2. INTRODUCTION .................................................................................................................5 
2.1. Study Objectives .......................................................................................................5 
2.2. Study Design .............................................................................................................7 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ..................................................................................................................9 
3.1. Primary Endpoints .....................................................................................................9 
3.2. Secondary Endpoints .................................................................................................9 
3.3. Secondary Efficacy Endpoints ................................................................................10 
3.3.1. Tertiary/Exploratory Endpoints ..................................................................10 
3.4. Baseline Variables ...................................................................................................10 
3.5. Safety Endpoints .....................................................................................................11 
3.5.1. Adverse Events ...........................................................................................11 
3.5.2. Laboratory Data ..........................................................................................11 
3.5.3. Vital Signs, including Height and Weight ..................................................12 
3.5.4. Physical Examinations ................................................................................12 
4. ANALYSIS SETS ...............................................................................................................12 
4.1. Full Analysis Set .....................................................................................................12 
4.2. Per Protocol Analysis Set ........................................................................................12 
4.3. Safety Analysis Set ..................................................................................................13 
5. GENERAL METHODOLOGY AND CONVENTIONS ....................................................13 
5.1. Hypotheses and Decision Rules ..............................................................................13 
5.1.1. Estimands ....................................................................................................13 
5.2. General Methods .....................................................................................................14 
5.2.1. Analysis of Primary Endpoint ....................................................................14 
5.2.2. Analysis of Other Biomarker Endpoints .....................................................15 
5.2.3. Analyses of Other Endpoints ......................................................................17 


Protocol B7451037 (PF-04965842) Statistical Analysis Plan 
 
 
PFIZER CONFIDENTIAL 
Page 3 
 

5.3. Methods to Manage Missing Data ..........................................................................17
6. ANALYSES AND SUMMARIES ......................................................................................17
6.1. Primary Endpoint ....................................................................................................17
6.1.1. Primary Analysis ........................................................................................18
6.1.2. Additional/Supportive Analysis ..................................................................18
6.2. Other Biomarker Endpoints ....................................................................................18
6.2.1. Primary Analysis ........................................................................................19
6.3. Efficacy Endpoints ..................................................................................................19
6.3.1. NRS4 for Severity Response ......................................................................19
6.3.2. IGA Response .............................................................................................20
6.3.3. EASI50, EASI75 and EASI90 Response ....................................................20
6.3.4. Change from Baseline in BSA% ................................................................20
6.4. Tertiary/Exploratory Endpoints ...............................................................................20

6.4.2. Night Time Itch Scale .................................................................................21
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6.5. PK Endpoints ...........................................................................................................21
6.6. Subset Analyses .......................................................................................................21
6.7. Baseline and Other Summaries and Analyses .........................................................22
6.7.1. Baseline Summaries ....................................................................................22
6.7.2. Study Conduct and Subject Disposition .....................................................22
6.7.3. Study Treatment Exposure .........................................................................22
6.7.4. Concomitant Medications and Non-drug Treatments .................................23
6.8. Safety Summaries and Analyses .............................................................................23
6.8.1. Adverse Events ...........................................................................................23
6.8.2. Laboratory Data ..........................................................................................23
6.8.3. Vital Signs ..................................................................................................24
6.8.4. Electrocardiogram .......................................................................................24
6.8.5. Physical Examination .................................................................................24
7. INTERIM ANALYSES .......................................................................................................24
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8. REFERENCES ....................................................................................................................24
9. APPENDICES .....................................................................................................................26
 
LIST OF TABLES 
Table 1. 
Summary of Changes ..................................................................................5 
Table 2 
Study Objectives and Endpoints .................................................................6 
 
LIST OF FIGURES 
Figure 1 
Study Design Schematic .............................................................................8 
 
APPENDICES 
Appendix 1. Summary of Clinical Efficacy Analyses .............................................................26 
Appendix 2. Definition and Use of Visit Windows in Reporting ............................................27 
 
Appendix 4. Investigator’s Global Assessment (IGA) ............................................................29 
Appendix 5. Eczema Area and Severity Index (EASI) ...........................................................30 
 
Appendix 7. Schedule of Activities .........................................................................................34 
 
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1. VERSION HISTORY 
This is the first amendment of the Statistical Analysis Plan (SAP) for Study 
B7451037 and is based on the final protocol dated 12NOV2020.  
Table 1. 
Summary of Changes  
Version/Date 
Associated Protocol 
Amendment 
Rationale 
Specific Changes 
1 
15 Oct 2019 
Protocol Amendment 1 
05 Sep 2019 
N/A 
N/A 
2 
29 Mar 2021 
Protocol Amendment 3 
12 Nov 2020 
Due to lack of assay of 
sufficient quality to 
study immature 
fraction.  
Section 2.1, 3.3.1, 4.3.1: 
Deleted “immature platelet 
fraction” and changed “platelet 
volume” to “platelet count, red 
blood cell count and 
reticulation”. 
 
 
For clarification and to 
add metabolites. 
Section 2.1: Updated PK 
objectives/endpoints. 
 
 
Suggestion by SciOps 
for clarification. 
Section 5.1: Added text to 
require baseline and a 12-week 
assessment. 
 
 
To allow for flexibility 
in analytical device. 
Section 5.2.2: Deleted text “by 
Illumina HiSeq 2500”. 
 
 
An interim analysis 
has been added. 
Section 7: Added text for 
interim analysis on the first 
15 completers of the trial. 
 
 
Hypothetical 
estimands are not the 
best approach in this 
case. 
Section 5.1.1 and 5.2.1: 
Deleted all references to a 
hypothetical estimand. 
 
 
Align with 
supplemental SAP. 
Section 5.2.2: Remove RNA 
analyses since they will be part 
of the supplementary 
biomarker SAP. 
3 
8 Sep 2021 
Protocol Amendment 3 
12 Nov 2020 
Clarify dose 
compliance derivation.  
Section 6.7.3: Added detailed 
derivation for dose compliance. 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of 
the data collected in Study B7451037.  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 
Study objectives and corresponding endpoints are provided in the Table 2 below. 


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Table 2 
Study Objectives and Endpoints 
Primary Objective: 
Primary Endpoint: 
To assess the 
PF-04965842on lesional 
and non-lesional skin 
biomarkers of adult 
participants with moderate 
to severe atopic dermatitis 
(AD). 
 
Changes from baseline in AD biomarkers in skin, including 
biomarkers for general inflammation (MM12), hyperplasia 
(K16), Th2 immune response (CCL17, CCL18, CCL26) and 
Th22 immune response (S100A8, S100A9, S100A12). 
Secondary Objectives: 
Secondary Endpoints: 
To evaluate the effect of 
PF-04965842 on gene 
expression (evaluated by 
mRNA PCR and/or gene 
arrays). 
 
Changes from baseline in gene expression (evaluated by mRNA 
PCR and/or gene arrays) over time in skin lesions. 
To evaluate the effect of 
PF-04965842 on 
inflammatory infiltrates 
(T-cell and dendritic cells) 
using 
immunohistochemistry 
IHC) in skin biopsies. 
 
Changes from baseline in cellular (T-cells and dendritic cells) 
markers using IHC in skin biopsies at various time points. 
To evaluate the effect of 
PF-04965842 on epidermal 
hyperplasia using IHC and 
RT PCR in skin biopsies. 
 
Changes from baseline in hyperplasia markers (thickness, 
K16, Ki67) in skin biopsies. 
To assess the effect of 
PF-04965842 on blood 
biomarkers (OLINK 
proteomic in serum). 
 
Changes from baseline in blood biomarkers (OLINK proteomic 
microassay for inflammation and immune response in serum). 
To assess changes in T-cell 
lymphocyte subset 
populations in blood using 
flow cytometry. 
 
Changes from baseline in T-cell lymphocyte subset populations 
in blood using flow cytometry. 
To evaluate the effect of 
PF-04965842 on pruritus 
and its correlation to IHC 
and genetic markers in 
lesional skin. 
 
Response based on at least 4 points improvement in the severity 
of Peak Pruritus numerical rating scale (NRS) from baseline and 
change from baseline in IHC and genetic markers in lesional 
skin. 
Efficacy Objectives: 
Efficacy Endpoints: 
To evaluate the effect of 
PF-04965842 on clinical 
efficacy outcomes. 
 
Response based on the Investigator's Global Assessment (IGA) 
score of clear (0) or almost clear (1) on a 5 point scale) and a 
reduction from baseline of ≥2 points at all scheduled time points. 
 
Response based on the Eczema Area and Severity Index 
≥75% improvement from baseline (EASI-75) response at all 
scheduled time points. 
 
Response based on at least 4 points improvement in the severity 
of Peak Pruritus NRS from baseline at all scheduled time points. 
 
Response based on a ≥50% and ≥90% improvement in the EASI 
total score (EASI-50 and EASI-90) at all scheduled time points. 


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x 
Change from baseline in the percentage Body Surface Area 
(BSA) affected at all scheduled time points. 
Safety Objectives 
Safety Endpoints 
To evaluate the safety and 
tolerability of 
PF-04965842 during 
12 weeks of treatment. 
x 
Incidence of treatment-emergent adverse events (TEAEs). 
x 
Incidence of serious AEs (SAEs). 
x 
Incidence of AEs leading to discontinuation. 
x 
Incidence of clinical abnormalities and changes from baseline in 
clinical laboratory values, and vital signs. 
Tertiary/Exploratory 
Objectives 
Tertiary/Exploratory Endpoints 
 
 
 
 
 
 
To assess the effect of 
PF-04965842 on 
Night Time Itch. 
x 
Changes from baseline in the Night Time Itch Scale at all 
scheduled time points. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2. Study Design 
This is a randomized, double-blind, placebo-controlled, parallel-group, Phase 2a 
study to investigate the mechanism of action of PF-04965842 by correlating efficacy 
outcomes with changes from baseline in key skin and blood biomarkers in adult 
participants 18 years of age with moderate-to-severe AD.  Participants will be 
screened within 28 days prior to the first dose of study intervention to confirm study 
eligibility.  A total of approximately 51 participants will be randomized in a 1:1:1 
ratio to receive PF-04965842 200 mg QD, PF-04965842 100 mg QD, or matching 
placebo QD for 12 weeks. A study design schematic is presented in Figure 1. 
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Figure 1 
Study Design Schematic 
 
At the end of the 12-week study treatment, qualified participants will have the option 
to enter the long-term extension (LTE) Study B7451015.  Participants discontinuing 
early from this study will undergo a 4-week off-treatment follow-up period. 
Eligible participants will be randomized into 3 intervention groups in the study: 
Group 1 (N=17): PF-04965842 200 mg QD taken orally for 12 weeks. 
Group 2 (N=17): PF-04965842 100 mg QD taken orally for 12 weeks. 
Group 3 (N=17): placebo QD taken orally for 12 weeks. 
The total duration of participation in the study is up to 20 weeks, including up to 
4 weeks for screening, 12 weeks study intervention, and a follow-up period of 
4 weeks after study intervention (for those participants who do not enter the LTE 
study).   
A full schedule of activities for the study is provided in Appendix 7. 
Sample Size Determination 
The sample size of this study is based on the objective to evaluate changes in key AD 
biomarkers in skin lesions, including biomarkers for general inflammation (MMP12), 


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hyperplasia (K16), Th2 (CCL17, CCL18, CCL26), and Th22 (S100A8, S100A9, 
S100A12) with PF 04965842 200 mg QD, PF 04965842 100 mg QD, and placebo. 
A total sample of approximately 51 participants, with 17 participants randomized to 
PF-04965842 200 mg QD, 17 participants randomized to PF-04965842 100 mg QD, 
17 participants randomized to matching placebo (1:1:1 randomization) is planned. 
A sample size of 17 participants per treatment group would provide about 92% 
chance that the 95% CI for the mean fold-change (post-baseline relative to baseline) 
has a half-width of no more than 3.2 (which is within 64% of an assumed maximal 
standard deviation of 5 for the fold-change, as based on published data).  Calculations 
are based on the assumption of a chi-square distribution for the variance so that the 
width of the estimated confidence interval is a random quantity. 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoints 
The primary endpoints are: 
 Changes from baseline in AD biomarkers in skin, including biomarkers for general 
inflammation (MMP12), hyperplasia (K16), Th2 immune response (CCL17, CCL18, 
CCL26), and Th22 immune response (S100A8, S100A9, S100A12). 
3.2. Secondary Endpoints 
The secondary endpoints are: 
 Changes from baseline in gene expression (evaluated by mRNA PCR and/or gene 
arrays) over time in skin lesions; 
 Changes from baseline in cellular (T cells and dendritic cells) markers using IHC in 
skin biopsies at various time points; 
 Changes from baseline in hyperplasia markers (thickness, K16, Ki67) in skin 
biopsies; 
 Changes from baseline in blood biomarkers (OLINK proteomic microassay for 
inflammation and immune response in serum); 
 Changes from baseline in T cell lymphocyte subset populations in blood using flow 
cytometry; 
 Change from baseline in IHC and genetic markers in lesional skin. 
A detailed description of how the pruritus NRS score is derived is provided in Appendix 3. 


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3.3. Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
x Response based on the Investigator's Global Assessment (IGA) score of clear (0) or 
almost clear (1) (on a 5 point scale) and a reduction from baseline of 2 points at all 
scheduled time points; 
x Response based on the Eczema Area and Severity Index 75% improvement from 
baseline (EASI 75) response at all scheduled time points; 
x Response based on at least 4 points improvement in the severity of Peak Pruritus NRS 
from baseline at all scheduled time points; 
x Response based on a 50% and 90% improvement in the EASI total score (EASI-50 
and EASI-90) at all scheduled time points; 
x Change from baseline in the percentage Body Surface Area (BSA) affected at all 
scheduled time points. 
3.3.1. Tertiary/Exploratory Endpoints 
x 
 
 
x Changes from baseline in Night Time Itch Scale at all scheduled time points; 
x
 
 
 
 
 
 
 
 
 
 
3.4. Baseline Variables 
In general, for all analyses, baseline will be defined based on observations collected 
prior to first dose.  Baseline values for demographics, medical and other history, 
atopic dermatitis history will be based on measures collected at Visit 1/Screening 
visit.  Study Day 1 is defined as the day the subject receives first dose of study drug.  
For purposes of all other analyses including analyses for change from baseline, the 
baseline value will be defined as measured on Day 1 (before time of first dose, if time 
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is available).  If a value is missing on Day 1, then the last available observation before 
Day 1 will be used. 
3.5. Safety Endpoints 
Safety will be assessed by the spontaneous reporting of AEs, physical examinations, 
and clinical laboratory results in all subjects who receive at least one dose of the 
investigational product.  Unscheduled safety assessments may be performed at any 
time during the study to assess any perceived safety concerns.  Endpoints will be 
assessed as: 
 Incidence of treatment emergent adverse events (AEs) and serious AEs (SAEs). 
 AEs leading to discontinuation. 
 Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
hospitalization or parenteral antimicrobials or met other criteria that required the 
event be classified as serious; 
 Incidence of clinical abnormalities and change from baseline in selected clinical 
laboratory values, ECG measurements, and vital signs. 
The safety endpoints will be defined in accordance with Clinical Data Interchange 
Standards Consortium (CDISC) aligned Pfizer Standards (CaPS). 
3.5.1. Adverse Events 
An adverse event will be considered a Treatment-Emergent Adverse Event (TEAE) if 
the event started during the effective duration of treatment.  All events that start on or 
after the first dosing day and time/start time, if collected, but before the last dose plus 
the lag time (28 days) will be flagged as TEAEs.  The algorithm will not consider any 
events that started prior to the first dose date.  
3.5.2. Laboratory Data 
Below is a list of hematology and serum chemistry test parameters. 
 Hematology: hemoglobin, hematocrit, red blood cell count, red blood cell 
indices (MCV, MCH, MCHC, RBC morphology), reticulocyte count, platelet 
count, white blood cell count with differential, total neutrophils, eosinophils, 
monocytes, basophils, lymphocytes, coagulation panel. 
 Clinical chemistry: blood urea nitrogen, creatinine, creatine phosphokinase, 
glucose (non-fasting, Day 1 and Week 12 fasting), sodium, potassium, 
chloride, calcium, total bicarbonate, aspartate aminotransferase, alanine 
aminotransferase, gamma-glutamyl transferase, bilirubin, alkaline 
phosphatase, lactate dehydrogenase, uric acid, albumin, total protein, total 
cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), 
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Below is a list of urinalysis test parameters 
 pH, glucose, protein, blood, ketones, nitrite, leukocyte esterase by dipstick; 
 Microscopic examination and/or culture. 
3.5.3. Vital Signs, including Height and Weight 
Vital sign measurements are temperature, respiratory rate, pulse rate and blood 
pressures. 
Height is collected at screening and weight is collected at pre- and post-treatment. 
3.5.4. Physical Examinations 
Complete physical examinations consist of assessments of general appearance; skin; 
head, eyes, ears, nose and throat; mouth, heart; lungs; breast (optional); abdomen; 
external genitalia (optional); extremities; neurologic function; and lymph nodes.  A 
targeted physical examination will include, at a minimum, assessments of the skin, 
heart, lungs, and abdomen and examination of body systems where there are 
symptom complaints by the participant. 
4. ANALYSIS SETS 
Data for all subjects will be assessed to determine if subjects meet the criteria for 
inclusion in each analysis population described below prior to unblinding and 
releasing the database and classifications will be documented per standard operating 
procedures. 
4.1. Full Analysis Set 
The Full Analysis Set (FAS) is defined as all subjects who have been randomized and 
who have received at least one dose study of treatment.  Subject is assigned to the 
randomized treatment group regardless of actual treatment received.  Analyses for 
endpoints that are defined based on a threshold of change from baseline (eg, NRS4) 
will also require the baseline value to be equal to or greater than that threshold (eg, 
for NRS4, the baseline value needs to be ≥4).  
4.2. Per Protocol Analysis Set 
The Per Protocol Analysis Set (PPAS) is defined as a subset of FAS who had no 
major protocol violations.  The subjects excluded from the PPAS will be determined 
and documented before the study is unblinded.  Supportive analyses for the primary 
endpoint will be performed using the PPAS.  This set will include subjects who:   
 Were eligible for the study by way of meeting key inclusion criteria and none 
of the key exclusion criteria. 
 Had valid and non-missing biopsies at baseline and per protocol schedule. 


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x Did not take a protocol-prohibited medication for the primary diagnosis prior 
to completion of the study dosing period (Visit 10/Week 12). 
x Took the correct randomized treatment for at least 80% and at most 120% of 
the assigned amount until completion of the study dosing period (Visit 
10/Week 12). 
x Had no other major protocol violations as determined by the clinical team 
prior to database lock.  A major protocol violation in this context is one that is 
likely to affect materially the efficacy responses of the patient and will be 
defined by the clinical team before database is locked and any analysis is 
performed for this study. 
These items will either be assessed by programmed checks of the data or be 
determined by clinical review prior to unblinding of study treatment. 
4.3. Safety Analysis Set 
The Safety Analysis Set (SAF) will be defined as all subjects who receive at least one 
dose of study medication classified according to actual study treatment received.  The 
safety analysis set is the primary population for treatment administration / compliance 
and safety.  A randomized but not treated subject will be excluded from the safety 
analyses.   
5. GENERAL METHODOLOGY AND CONVENTIONS 
The final analysis and reporting of results will be performed after the completion of 
the study and the database is locked. 
5.1. Hypotheses and Decision Rules 
There will be no formal hypothesis testing, but the point estimates and 95% two-sided 
confidence intervals will be reported for the biomarker endpoints, secondary efficacy 
 endpoints.  No adjustments for multiplicity will be 
performed.  Safety endpoints will be summarized descriptively through appropriate 
data tabulations, descriptive statistics, categorical summaries, and graphical 
presentations. 
5.1.1. Estimands 
The primary objective of this study is to assess the effects of PF-04965842 on lesional 
and non-lesional skin biomarkers of adult participants with moderate-to-severe AD.  
A hypothetical estimand will be used for estimation.  The following estimand 
attributes will be considered: 
x Population: Participants with moderate-to-severe AD as defined by the inclusion 
criteria and with a valid baseline and Week 12 assessment;  
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 Variable: Fold-change from baseline in the biomarkers for general inflammation 
(MMP12), hyperplasia (K16), Th2 immune response (CCL17, CCL18, CCL26), and 
Th22 immune response (S100A8, S100A9, S100A12); 
 Intercurrent event: All data collected will be utilized; 
 Population-level summary: Mean fold-change from baseline within each treatment 
group. 
Some secondary objectives require analyses of binary endpoints for which, a 
composite estimand with the following attributes will be considered:  
 Population: Participants with moderate-to-severe AD as defined by the inclusion 
criteria and with a valid baseline; 
 Variable: Binary outcome measures such as responder-based endpoints.  Participants 
who discontinue from the study treatment for any reason are defined as 
non-responders after that point; 
 Intercurrent event: The intercurrent event is captured through the variable definition; 
 Population-level summary: Proportion of participants who are responders in each 
treatment group and differences in proportions of responders between each active 
dose and placebo. 
5.2. General Methods 
In general, for descriptive analyses, number and percent will be presented for binary 
endpoints.  Number, median, Q1 and Q3 will be presented for descriptive analyses of 
continuous efficacy endpoints.  
5.2.1. Analysis of Primary Endpoint 
The population for the primary analysis will be all participants in the FAS having 
valid biomarker data at baseline and Week 12.  
The primary endpoints in this study include mean fold-changes for the following 
biomarkers:  
 General inflammation (MMP12);  
 Hyperplasia (K16);  
 Th2 (CCL17, CCL18, CCL26);  
 Th22 (S100A8, S100A9, S100A12). 


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In each participant, expression levels from RT-PCR will be normalized to the 
housekeeping gene RPLP0 (validated in other studies) by negatively transforming the 
Ct values to –dCt, obtaining an equivalent to log2 scale expression values (reporting 
unit: log2 [Expression/RPLP0]).  The expression values below detection will be 
estimated for each gene as the 20% of the minimum of unlogged values across all 
samples (which is equivalent to subtracting 2.321928 from the –dCt minimum value).  
The expression levels below detection may provide important information about some 
markers that significantly change with treatment (eg, the expression may decrease 
below the level of detection after treatment), therefore this imputation is an important 
step in the analysis.   
RT-PCR expression data in log2 scale will be modeled using a mixed effect model 
with Treatment, Time Point, and Tissue Type as a fixed effect and a random intercept 
for each participant.  This model will yield unbiased estimates and valid inferences in 
the presence of a missing data mechanism that is missing at random (MAR).1  This 
approach introduces less bias than restricting the analysis for participants with 
complete observations.  Contrasts will be used to estimate the log2 fold-changes for 
each treatment group.  Fold-changes will be computed by obtaining the antilog of 
log2 fold-changes.  Point estimates and 95% confidence intervals (CIs) will be 
obtained for the fold-change from baseline in the biomarker values for each treatment 
group based on this model. 
Correlation analyses will be performed to assess if the fold-change from baseline in 
biomarkers correlates with change (from baseline) in the clinical efficacy endpoints 
such as IGA, EASI, and Peak Pruritus NRS. 
Supportive analyses for the primary endpoint will also be performed using the PPAS.  
While statistical tests of hypotheses will not be performed to compare the fold-change 
from baseline in the PF-04965842 groups versus placebo, the point estimates and 
95% CIs for the two PF-04965842 dose groups will be assessed in relation to those 
from the placebo group.  A fold-change from baseline observed in the PF-04965842 
groups alone (and correlated with efficacy) but not in the placebo group is likely due 
to the mechanism of action of PF-04965842. 
5.2.2. Analysis of Other Biomarker Endpoints 
In addition to the key biomarkers considered as primary endpoints, the other 
biomarkers endpoints in this study include (but may not be limited to) the following: 
Parameters studied using IHC will include epidermal thickness (performed on H&E 
sections), Ki 67+ cells, Keratin 16 (K16), 
 
 
. 
 
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Gene expression by TLDA RT-PCR will include the levels of the following 
established cytokines associated with AD:
 
 
S100A7, S100A8, S100A9, S100A12, 
 
 CCL18, 
 CCL26, 
 18S and 
RPLP0 as control genes.   
 
 
 
 
 
 
 
 
 
 
 
The mixed-effect model approach chosen for the analysis of RT-PCR and IHC data 
has the advantage that estimation of the parameters in the models is unbiased and 
valid inferences are possible in the presence of a missing data mechanism that is 
MAR.  This approach introduces less bias than restricting the analysis for participants 
with complete observations. 
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5.2.3. Analyses of Other Endpoints 
The responses based on IGA, EASI (eg, EASI-75), and severity scale of the Peak 
Pruritus NRS will be summarized descriptively by visit and treatment.  The difference 
of the improvement from baseline between each PF-04965842 dose and placebo will 
also be derived. 
If a participant withdraws from the study, then this participant will be considered a 
non-responder after withdrawal for any binary valued clinical efficacy endpoint. 
 
 
 
 
 
 
 
5.3. Methods to Manage Missing Data 
In general, for analyses using descriptive statistics, missing values will not be 
explicitly imputed.  In addition, for safety endpoints, missing values will not be 
imputed.   
For the responses based on IGA, EASI (eg, EASI-75), and severity scale of the Peak 
Pruritus NRS, if a participant withdraws from the study, then this participant will be 
considered a non-responder after withdrawal for any binary valued clinical efficacy 
endpoint. 
6. ANALYSES AND SUMMARIES 
Point estimates and 95% confidence intervals will be provided for each of the 
PF-04965842 QD treated groups (200 mg and 100 mg) and placebo.  
A summary of analyses for clinical efficacy endpoints is provided in Appendix 1.  
Visit windows to be used for all efficacy analyses and some relevant safety analyses 
are detailed in Appendix 2. 
Data collected at Week 16 will be displayed in listings only, and will not be part of 
any analyses, unless specifically noted otherwise. 
6.1. Primary Endpoint 
The primary endpoints in this study include mean fold-changes for the following 
biomarkers:  
x General inflammation (MMP12);  
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x Hyperplasia (K16);  
x Th2 (CCL17, CCL18, CCL26);  
x Th22 (S100A8, S100A9, S100A12). 
6.1.1. Primary Analysis 
x Summary: Fold-change from baseline at Week 12; 
x Population: FAS; 
x Statistical Method: Estimate and 95% CI from MMRM described in 
Section 5.2.1; 
x Missing Data: No explicit imputation. 
6.1.2. Additional/Supportive Analysis 
x Summary: Fold-change from baseline at Week 12; 
x Population: PPAS; 
x Statistical Method: Estimate and 95% CI from MMRM described in 
Section 5.2.1; 
x Missing Data: No explicit imputation. 
6.2. Other Biomarker Endpoints 
The other biomarker endpoints in this study include mean fold-changes for the 
following biomarkers:  
x epidermal thickness (performed on H&E sections);  
x Ki 67+ cells,  
x Keratin 16 (K16);  
x 
  
 
 
 
 
 
 
 
 
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x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.2.1. Primary Analysis 
x Summary: Fold-change from baseline at Week 12; 
x Population: FAS; 
x Statistical Method: Estimate and 95% CI from MMRM described in 
Section 5.2.2; 
x Missing Data: No explicit imputation. 
6.3. Efficacy Endpoints 
6.3.1. NRS4 for Severity Response 
x Summary: Proportion of subjects with NRS4 for severity response at Weeks 4, 
8 and 12; 
x Population: Subjects from the FAS with a baseline NRS score for severity 4; 
x Statistical Method: Descriptive (n, %), 95% CI and difference from placebo. 
Visit windows will be used as described in Appendix 2; 
x Missing Data: Missing data arising due to subject dropout are considered 
“non-response”. 
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6.3.2. IGA Response 
x Summary: Proportion of subjects with IGA score of clear (0) or almost 
clear (1) and a reduction from baseline of t2 points at Weeks 2, 4, 8 and 12; 
x Population: Subjects from the FAS with a baseline IGA score 2; 
x Statistical Method: Descriptive (n, %). Visit windows will be used as 
described in Appendix 2; 
x Missing Data: Missing data arising due to subject dropout are considered 
“non-response”. 
6.3.3. EASI50, EASI75 and EASI90 Response 
x Summary: Proportion of subjects with EASI response at Weeks 2, 4, 8 and 12; 
x Population: FAS; 
x Statistical Method: Descriptive (n, %). Visit windows will be used as 
described in Appendix 2; 
x Missing Data: Missing data arising due to subject dropout are considered 
“non-response”. 
6.3.4. Change from Baseline in BSA% 
x Summary: Change from baseline at all scheduled visits; 
x Population: FAS; 
x Statistical Method: Descriptive (LSmean, SD, mean difference, SE, 95% CI, 
median, Q1, Q3); 
x Missing Data: Observed Data. 
 
 
  
 
 
 
 
 
 
 
 
   
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6.4.2. Night Time Itch Scale  
x Summary: Change from baseline in Night Time Itch Scale at all scheduled 
visits; 
x Population: FAS; 
x Statistical Method: Descriptive (mean, SD, median, Q1, Q3); 
x Missing Data: Observed data. 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
6.5. PK Endpoints 
PK concentration data for PF-04965842 and its metabolites will be summarized 
through appropriate data tabulations, descriptive statistics, and graphical presentation.  
A population PK model will be developed for the purpose of estimating PK 
parameters.  Additional details of the methodology will be captured in a separate 
modeling plan and the results will also be reported separately. 
6.6. Subset Analyses 
Summary statistics for co-primary endpoints will be presented by subgroups below. 
x Age (years) group; (<40, 40); 
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 Race (White, Black or African-American, Asian, Other1); 
 Baseline disease severity (moderate, severe). 
Point estimates and 95% confidence intervals will be derived from MMRM models as 
described in Section 5.2.1.  
The primary purpose of the subgroup analyses is to check for consistency of results 
across subgroups, to make sure overall results are not being driven by some subset of 
subjects. 
Graphical display (eg, forest plots) of the differences between treatment groups will 
be presented.  There is no intention to have any specific inference within subgroups. 
6.7. Baseline and Other Summaries and Analyses 
6.7.1. Baseline Summaries 
Demographics, medical history, primary diagnosis, history of prior AD treatments 
and disease characteristics will be summarized by treatment group according to CaPS. 
6.7.2. Study Conduct and Subject Disposition 
Subjects’ evaluation, disposition and discontinuation will be summarized according to 
CaPS. 
6.7.3. Study Treatment Exposure 
Subjects were expected to take 2 tablets of 100 mg per day (on a QD schedule) during the 12 
weeks treatment period. The study drug compliance is defined as: 
Drug compliance (%) = 100×Actual number tablets taken/Expected number of tablets, 
where 
Actual number tablets taken = Total number of dispensing tablets [at Week 0 (Day 1), 4, and 
8] – Total number of return tablets (at Weeks 4, 8, and 12); 
Expected number of tablets = 2×Days of treatment duration (Last treatment date – First 
treatment date +1). 
The study compliance (%) and study durations (days) will be summarized for each treatment 
group. 
                                                 
1 For purposes of analysis, Other will comprise the categories of American Indian or Alaska Native, 
Hawaiian or Other Pacific Islander, Multi-Racial and any other category reported on the CRF. 


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6.7.4. Concomitant Medications and Non-drug Treatments 
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to CaPS. 
6.8. Safety Summaries and Analyses 
Safety analyses will be based on the SAF analysis set. 
All clinical AEs, SAEs, TEAEs, withdrawal due to AEs, ECGs, vital signs and safety 
laboratory data will be reviewed and summarized on an ongoing basis during the 
study to evaluate the safety of subjects. 
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 CaPS.  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. 
6.8.1. Adverse Events 
The safety data will be summarized in accordance with CaPS.  All safety data will be 
summarized descriptively through appropriate data tabulations, descriptive statistics, 
categorical summaries, and graphical presentations.  Safety endpoints for the study 
include: 
x Treatment-emergent AEs and SAEs; 
x Withdrawals from active treatment due to AEs; 
x Serious infections, defined as any infection (viral, bacterial, and fungal) 
requiring hospitalization or parenteral antimicrobials. 
AEs will be displayed by MedDRA system organ class (SOC). 
It should be recognized that most studies are not designed to reliably demonstrate a 
causal relationship between the use of a pharmaceutical product and an adverse event 
or a group of adverse events.  Except for select events in unique situations, studies do 
not employ formal adjudication procedures for the purpose of event classification.  
 
 
   
6.8.2. Laboratory Data 
Laboratory data will be listed and summarized in accordance with the CaPS reporting 
standards.  Summaries of subjects meeting pre-specified monitoring and 
discontinuation criteria will be created using methods for categorical data. 
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6.8.3. Vital Signs 
Vital signs will be summarized at baseline, Weeks 2, 4, 8, and 12/End of Treatment 
visits.  Height and weight will be summarized at baseline (both) and End of 
Treatment (weight only) visits. 
6.8.4. Electrocardiogram 
ECG parameters, if applicable, will be summarized at baseline 
6.8.5. Physical Examination 
Physical examinations will be summarized at baseline and all-available post-baseline 
visits. 
The C-SSRS will also be collected and reported using descriptive summaries for 
recent history/baseline and post-baseline visits. 
7. INTERIM ANALYSES 
After the first 15 participants have completed the trial, there will be an interim 
analysis to examine platelet values.  A longitudinal analysis will be conducted to 
determine if there is a change from baseline in platelet values.  The data will remain 
blinded so that no one will know the participants’ assigned treatment and thus the 
analysis will not look for any treatment differences.  Correlation analyses may also be 
conducted to look for potential relationships between platelet values and other 
laboratory measures, such as TPO.  There will not be any decision rules associated 
with this interim analysis, so there will be no changes to the conduct or continuation 
of the trial based on these analyses. 
There will be a program-level E-DMC (see below) who will periodically review the 
safety data from the study. 
This study will use an E-DMC.  The E-DMC is independent of the study team and 
includes only external members.  The E-DMC will be responsible for ongoing 
monitoring of the safety of participants in the study according to the charter.  
The recommendations made by the E-DMC to alter the conduct of the study will be 
forwarded to Pfizer for final decision.  Pfizer will forward such decisions, which may 
include summaries of aggregate analyses of endpoint events and of safety data that 
are not endpoints, to regulatory authorities, as appropriate.  Composition of the 
E-DMC and processes under which the E-DMC operates will be documented in the 
E-DMC charter. 
8. REFERENCES 
1. 
R Core Team (2018). R: A language and environment for statistical computing. 
R Foundation for Statistical Computing, Vienna, Austria. URL 
https://www.R-project.org/.  


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9. APPENDICES 
Appendix 1. Summary of Clinical Efficacy Analyses 
Efficacy Endpoints 
Population 
Analysis 
Method 
Missing 
Data 
Imputation 
Primary 
Analysis 
for 
Co-primary 
Week 12 IGA 
Response 
 
FAS 
CMH 
NR 
Yes 
PPAS 
CMH 
NR 
No 
Week 12 
EASI-75 Response 
 
FAS 
CMH 
NR 
Yes 
PPAS 
CMH 
NR 
No 
Weeks 2, 4, 8 and 12 
NRS4 for severity 
Response 
 
FAS 
CMH 
NR+MI 
 
PPAS 
CMH 
NR+MI 
 
FAS 
CMH 
NR 
 
Time to NRS4 for 
severity 
FAS 
Kaplan-
Meier 
OD 
 
Weeks 2, 4 and 
8 IGA Response 
FAS 
CMH 
NR 
 
Weeks 2, 4, 8 and 
12 EASI-50 / EASI-
90 / EASI-
100 Response 
FAS 
CMH 
NR 
 
Weeks 2, 4 and 
8 EASI-75 Response 
FAS 
CMH 
NR 
 
Weeks 2, 4, 8 and 
12 CFBL in Total 
EASI Score 
FAS 
MMRM 
OD 
 
Weeks 2, 4, 8 and 
12 CFBL in NRS for 
severity 
FAS 
MMRM 
OD 
 
Weeks 2, 4, 8 and 
12 CFBL in %BSA 
FAS 
MMRM 
OD 
 
CFBL=Change from baseline; CMH=Cochran-Mantel-Haenszel; ANCOVA=Analysis of Covariance; 
MMRM=Mixed-effect Model Repeated Measures; NR=Non-Responder; OD=Observed Data; MI=Multiple Imputation.   
 


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Appendix 2. Definition and Use of Visit Windows in Reporting 
Visit windows will be used for efficacy variables, and for any safety data that display 
or summarize by study visit.  For other endpoints (eg, ECG, vital signs), visit 
windows will be applied for summary statistics by study visits if required. 
Visit Label 
Target Day 
Definition [Day window] 
Screening 
 
Days -28 to Day -1 
Baseline 
Day 1 (Day of 
first dose) 
Last observation prior to 
and including day of first 
dose 
Week 2 
15 
Days 2 to 22 
Week 4 
29 
Days 23 to 36 
Week 6 
43 
Days 37 to 50 
Week 8 
57 
Days 51 to 71 
Week 12 
85 
Days 72 to 99 
Follow Up/End of 
Study 
 
 
Week 16 
- 
Days 100 to - 
For the lab values, if the calculated study day for the labelled baseline visit is not 
study Day 1, but falls within 28 days before the start of the study dosing, then that 
data should be used for the baseline instead of leaving baseline missing. 
For the other values, if the calculated study day for the labelled baseline visit is not 
study Day 1, but falls before the start of the study dosing, then that data should be 
used for the baseline instead of leaving baseline missing. 
If two or more visits fall into the same window, keep the one closest to the Target 
Day.  If two visits are equaled distant from the Target Day in absolute value, the later 
visit should be used. 
Safety analysis may follow CaPS standards. 
 


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Appendix 4. Investigator’s Global Assessment (IGA) 
The Investigator’s Global Assessment of atopic dermatitis is scored on a 5-point scale 
(0-4), reflecting a global consideration of the erythema, induration and scaling.  The 
clinical evaluator of atopic dermatitis will perform an assessment of the overall 
severity of atopic dermatitis and assign an IGA score and category as described in the 
table below.  The assessment will be a static evaluation without regard to the score at 
a previous visit. 
IGA Score 
Score 
Category 
Description 
0 
Clear 
Atopic dermatitis is cleared, except for any residual 
discoloration (post-inflammatory hyperpigmentation and/or 
hypopigmentation). 
1 
Almost 
Clear 
Overall, the atopic dermatitis is not entirely cleared and 
remaining lesions are light pink (not including post 
inflammatory hyperpigmentation) and/or; have barely 
palpable hard thickened skin and/or papules and/or; have 
barely perceptible lichenification; excoriation and 
oozing/crusting are absent. 
2 
Mild 
Overall, the atopic dermatitis consists of lesions that are 
light red; with slight, but definite hard thickened skin 
and/or papules; with slight, but definite linear or picked 
scratch marks or penetrating surface injury; with slight, but 
definite thickened skin, fine skin markings, and lichenoid 
scale; oozing/crusting is absent. 
3 
Moderate 
Overall, the atopic dermatitis consists of lesions that are 
red; with easily palpable moderate hard thickened skin 
and/or papules; with moderate linear or picked scratch 
marks or penetrating surface injury; with moderate 
thickened skin, coarse skin markings, and coarse lichenoid 
scale; with slight oozing/crusting. 
4 
Severe 
Overall, the atopic dermatitis consists of lesions that are 
deep, dark red; with severe hard thickened skin and/or 
papules; with severe linear or picked scratch marks or 
penetrating surface injury; with severe thickened skin with 
very coarse skin markings and lichenoid scale; with 
moderate to severe oozing/crusting. 
 


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Appendix 5. Eczema Area and Severity Index (EASI) 
The EASI quantifies the severity of a subject’s atopic dermatitis based on both 
severity of lesion clinical signs and the percent of BSA affected.  EASI is a composite 
scoring by the atopic dermatitis clinical evaluator of the degree of erythema, 
induration/papulation, excoriation, and lichenification (each scored separately) for 
each of four body regions, with adjustment for the percent of BSA involved for each 
body region and for the proportion of the body region to the whole body. 
Lesion Severity by Clinical Signs: The basic characteristics of atopic dermatitis 
lesions-erythema, induration/papulation, excoriation, and lichenification-provide a 
means for assessing the severity of lesions.  Assessment of these four main clinical 
signs is performed separately for four body regions: head and neck, upper limbs, 
trunk (including axillae and groin) and lower limbs (including buttocks).  Average 
erythema, induration/papulation, excoriation, and lichenification are scored for each 
body region according to a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe.  
Morphologic descriptors for each clinical sign severity score are shown in the table 
below. 
Clinical Sign Severity Scoring Criteria for the EASI 
Score 
Description 
Erythema (E) 
0 
Absent 
None; may have residual discoloration (post-inflammatory 
hyperpigmentation and/or hypopigmentation). 
1 
Mild 
Light pink to light red 
2 
Moderate 
Red 
3 
Severe 
Deep, dark red 
Induration/Papulation (I) 
0 
Absent 
None 
1 
Mild 
Barely palpable to slight, but definite hard thickened skin and/or 
papules 
2 
Moderate 
Easily palpable moderate hard thickened skin and/or papules 
3 
Severe 
Severe hard thickened skin and/or papules 
Excoriation (Ex) 
0 
Absent 
None 
1 
Mild 
Slight, but definite linear or picked scratch marks or penetrating 
surface injury 
2 
Moderate 
Moderate linear or picked scratch marks or penetrating surface 
injury 
3 
Severe 
Severe linear or picked scratch marks or penetrating surface 
injury 
Lichenification (L) 
0 
Absent 
None 
1 
Mild 
Barely perceptible to slight, but definite thickened skin, fine skin 
markings, and lichenoid scale 
2 
Moderate 
Moderate thickened skin, coarse skin markings, and coarse 
lichenoid scale 
3 
Severe 
Severe thickened skin with very coarse skin markings and 
lichenoid scale 


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%BSA with Atopic Dermatitis: The number of handprints of skin afflicted with atopic 
dermatitis in a body region can be used to determine the extent (%) to which a body region is 
involved with atopic dermatitis (see table below).  When measuring, the handprint unit refers 
to the size of each individual subject’s hand with fingers in a closed position. 
Handprint Determination of %BSA 
Body Region 
Total Number of 
Handprints in 
Body Region* 
Surface Area of 
Body Region 
Equivalent of One 
Handprint* 
Head and Neck 
10 
10% 
Upper Limbs 
20 
5% 
Trunk (including axillae 
and groin/genitals) 
30 
3.33% 
Lower Limbs (including 
buttocks) 
40 
2.5% 
Handprint refers to the hand size of each individual subject. 
* The number of handprints will be for the entire body region. 
EASI Area Score Criteria 
Percent BSA with Atopic Dermatitis in a Body 
Region 
Area Score 
0% 
0 
>0 - <10% 
1 
10 - <30% 
2 
30 - <50% 
3 
50 - <70% 
4 
70 - <90% 
5 
90 - 100% 
6 
Body Region Weighting: Each body region is weighted according to its approximate 
percentage of the whole body (see table below). 
EASI Body Region Weighting 
Body Region 
Body Region Weighting 
Head and Neck 
0.1 
Upper Limbs 
0.2 
Trunk (including axillae and 
groin/genitals) 
0.3 
Lower Limbs (including 
buttocks) 
0.4 
* No adjustment for body regions excluded for assessment. 


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In each body region, the sum of the Clinical Signs Severity Scores for erythema, 
induration/papulation, excoriation, and lichenification is multiplied by the Area 
Score and by the Body Region Weighting to provide a body region value, which is 
then summed across all four body regions resulting in an EASI score as described in 
Equation below. 
EASI    = 
0.1Ah(Eh+Ih+Exh+Lh) + 0.2Au(Eu+Iu+ExU+Lu) + 
0.3At(Et+It+Ext+Lt) + 0.4Al(El+Il+Exl+Ll) 
A = Area Score; E = erythema; I = induration/papulation; Ex = excoriation; 
L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs 
The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores 
representing greater severity of atopic dermatitis. 
 


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Appendix 7. Schedule of Activities 
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY 
PROCEDURES and ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment 
required for compliance with the protocol.  
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject. 
 
Screening 
Intervention Period 
Follow-up Notes 
Visit Identifier  
Day -28 
Day 1 
Week 0 
Base line 
Day 2 
Week 0 
Day 4 
Week 0 
Day 8 
Week 1 
(by 
Phone) 
Day 15 
Week 2 
Day 29 
Week 4 
Day 43 
Week 6 
(by 
Phone) 
Day 57 
Week 8 
Day 85 
Week 12 
(EOT/ET)  
Day 113 
Week 16 
(EOS) 
Visit 11 is 4 weeks 
after last dose in case 
of early study 
termination.  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
 
Visit Window (days) 
None 
None 
None 
1 
1 
1 
2 
3 
3 
3 
3 
 
Enrollment Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Register participant using 
IRT 
X 
 
 
 
 
 
 
 
 
 
 
See Section 6.3  
Inclusion and exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
See Section 5.1 and 
Section 5.2  
Demographics, medical 
history, tobacco and alcohol 
history, AD disease history 
and prior AD treatments 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1 
Review prior/concomitant 
medications & treatments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Provide patient emergency 
contact card 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
examination  
X 
 
 
 
 
 
 
 
 
X 
 
See Section 8.2.1  
Targeted physical exam 
 
X 
 
 
 
X 
X 
 
X 
 
X 
Vital signs (blood pressure, 
pulse rate, respiratory rate, 
temperature) 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
See Section 8.2.2 


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Screening 
Intervention Period 
Follow-up Notes 
Visit Identifier  
Day -28 
Day 1 
Week 0 
Base line 
Day 2 
Week 0 
Day 4 
Week 0 
Day 8 
Week 1 
(by 
Phone) 
Day 15 
Week 2 
Day 29 
Week 4 
Day 43 
Week 6 
(by 
Phone) 
Day 57 
Week 8 
Day 85 
Week 12 
(EOT/ET)  
Day 113 
Week 16 
(EOS) 
Visit 11 is 4 weeks 
after last dose in case 
of early study 
termination.  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
 
Weight 
X 
 
 
 
 
 
 
 
 
X 
 
See Section 8.2.1 
Height 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.3  
ECG (12-lead) 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.7 
Laboratory Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistry and 
hematology (including 
coagulation panel) 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
See Appendix 2.  See 
Section 8.2.8 for 
guidance on 
abnormal lab results 
Lipid panel 
 
X 
 
 
 
 
 
 
 
X 
 
8-hour fast required 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
Fresh blood collection for 
hematopoiesis evaluation 
 
X 
 
X 
 
X 
X 
 
X 
X 
X 
See Section 
8.18 Collected from 
participants at 
participating sites  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 See 
Section 8.5  
Lymphocyte subsets  
 
X 
 
X 
 
X 
 
 
X 
X 
X 
See Appendix 2 
Urinalysis  
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
See Appendix 2 
Serum pregnancy test  
X 
 
 
 
 
 
 
 
 
 
 
Required for all 
WOCBP 
Urine Pregnancy Test 
(conducted at study site) 
 
X 
 
 
 
X 
X 
 
X 
X 
X 
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Screening 
Intervention Period 
Follow-up Notes 
Visit Identifier  
Day -28 
Day 1 
Week 0 
Base line 
Day 2 
Week 0 
Day 4 
Week 0 
Day 8 
Week 1 
(by 
Phone) 
Day 15 
Week 2 
Day 29 
Week 4 
Day 43 
Week 6 
(by 
Phone) 
Day 57 
Week 8 
Day 85 
Week 12 
(EOT/ET)  
Day 113 
Week 16 
(EOS) 
Visit 11 is 4 weeks 
after last dose in case 
of early study 
termination.  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
 
Banked Biospecimen Sample 
(Prep D1)  
 
X 
 
 
 
 
 
 
 
 
 
See Section 8.7.2  
If not collected on 
the designated 
collection day, 
collect at the next 
available time point 
when biospecimens 
are being collected in 
conjunction with a 
participant visit 
Banked Biospecimen Sample 
(Prep B1.5)  
 
X 
 
 
 
 
 
 
 
X 
 
See Section 8.8.4  
Banked Biospecimen Sample 
(Prep B2.5)  
 
X 
 
 
 
 
 
 
 
X 
 
See Section 8.8.4  
Blood samples collection for 
viral studies 
 
X 
 
 
 
 
 
 
 
 
 
Only analyzed on 
suspected viral 
infection/reactivation
.  See Section 8.2.8.2  
HIV testing  
X 
 
 
 
 
 
 
 
 
 
 
See Appendix 2 
Hepatitis B (HBsAg, HBsAb 
and HBcAb) and Hepatitis C 
(HCV Ab, HCV RNA)  
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.8.1 
HBV DNA (Only when 
HBsAg-, HBcAb+, HBsAb+ 
at screening) 
X 
 
 
 
 
 
 
 
 
X 
 
See Section 8.2.8.1 
Tuberculosis test 
X 
 
 
 
 
 
 
 
 
 
 
See Section 5.2 and 
Section 8.2.4 
Study Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
Drug dispensing 
 
X 
 
 
 
 
X 
 
X 
 
 
 
Drug accountability   
 
 
 
 
 
X 
X 
 
X 
X 
 
 


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Screening 
Intervention Period 
Follow-up Notes 
Visit Identifier  
Day -28 
Day 1 
Week 0 
Base line 
Day 2 
Week 0 
Day 4 
Week 0 
Day 8 
Week 1 
(by 
Phone) 
Day 15 
Week 2 
Day 29 
Week 4 
Day 43 
Week 6 
(by 
Phone) 
Day 57 
Week 8 
Day 85 
Week 12 
(EOT/ET)  
Day 113 
Week 16 
(EOS) 
Visit 11 is 4 weeks 
after last dose in case 
of early study 
termination.  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
 
Study intervention treatment 
 
X-----------------------------------------------------------------------------------------------------X 
 
At Weeks 4 and 12, 
study intervention 
treatment should be 
taken at the study 
site to accommodate 
PK analysis. See 
Section 8.5  
Assess eligibility for LTE 
Study B7451015 
 
 
 
 
 
 
 
 
 
X 
 
 
Clinical Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
Fitzpatrick Skin Type 
Assessment 
 
X 
 
 
 
 
 
 
 
 
 
See Section 8.2.6   
Investigator’s Global 
Assessment (IGA)  
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
See Section 8.1.6   
Eczema Area and Severity 
Index (EASI) 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
See Section 8.1.7   
Skin Biopsies 
 
 
 
 
 
 
 
 
 
 
 
 
Target lesion(s) identification 
 
X 
 
 
 
 
 
 
 
 
 
See Section 8.1.2  
Lesional skin punch biopsy 
sampling 
 
X 
 
 
 
X 
(Optional
) 
X 
 
 
X 
 
See Section 8.1.2  
Non-lesional skin punch 
biopsy sampling 
 
X 
 
 
 
 
 
 
 
X (Optional) 
 
See Section 8.1.2  
Examination of Post-biopsy 
Site(s) 
 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
See Section 8.1.2  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
Photography 
 
X 
 
 
 
 
X 
 
 
X 
 
See Section 8.1.5   
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Screening 
Intervention Period 
Follow-up Notes 
Visit Identifier  
Day -28 
Day 1 
Week 0 
Base line 
Day 2 
Week 0 
Day 4 
Week 0 
Day 8 
Week 1 
(by 
Phone) 
Day 15 
Week 2 
Day 29 
Week 4 
Day 43 
Week 6 
(by 
Phone) 
Day 57 
Week 8 
Day 85 
Week 12 
(EOT/ET)  
Day 113 
Week 16 
(EOS) 
Visit 11 is 4 weeks 
after last dose in case 
of early study 
termination.  
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
 
Patient-reported Outcomes 
(PRO) 
 
 
 
 
 
 
 
 
 
 
 
 
Peak Pruritus Numerical 
Rating Scale (NRS)  
X------X 
X---------------------------------------------------X 
X 
 
X 
X 
X 
See Section 
8.1.9.1.  During 
screening, assessed 
for the 7 days prior 
to Day 1 and also 
each day from Day 1 
to Day 15  
Night Time Itch Scale 
X------X 
X---------------------------------------------------X 
X 
 
X 
X 
X 
See Section 8.1.9.2. 
During screening, 
assessed for the 
7 days prior to Day 1 
and also each day 
from Day 1 to 
Day 15.  
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
C-SSRS 
X 
X 
 
 
 
 
 
 
X 
X 
X 
See Section 8.2.9.1  
PHQ-8 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.9.2 
Serious and non-serious 
adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Contraception check 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Required for all 
females 
Abbreviations: AD = atopic dermatitis; C-SSRS = Columbia Suicide Severity Rating Scale; EASI = Eczema Area and Severity Index, ECG = electrocardiogram; EOS = End of 
Study, EOT = End of Treatment; ET= early termination; HBsAg = hepatitis B surface antigen; HBsAb = hepatitis B surface antibody; HBcAb = hepatitis B core antibody; HBV 
DNA = hepatitis B viral deoxyribonucleic acid, HCV Ab = hepatitis C antibody; HCV RNA = hepatitis C viral ribonucleic acid; HIV = human immunodeficiency virus; 
hsCRP = high sensitivity C-reactive protein, IGA = Investigator’s Global Assessment; IRT = Interactive Response System; LS = lesional; LTE = long-term extension;  
NL = non-lesional; NRS = Numerical Rating System; PHQ-8 = Patient Health Questionnaire - 8 Items; PK = Pharmacokinetic; WOCBP = women of childbearing potential.