Clinical trial NCT04345367
Conditions: Atopic Dermatitis
Keywords: atopic dermatitis atopic eczema eczema JAK janus kinase
Sponsor: Pfizer
Start date: 2020-06-11; Completion date: 2021-07-13
Enrollment: 727 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blind, double-dummy, active-controlled, multi-center study to assess the efficacy and safety of abrocitinib 200 mg (2 x 100 mg tablets) administered orally QD compared with dupilumab 300 mg administered by subcutaneous injection every other week (as per label guidelines) in adult participants on background topical therapy, with moderate to severe AD. The treatment duration is 26 weeks. A total of approximately 600 participants will be enrolled from approximately 220 sites globally. Approximately 600 participants will be randomly assigned to study intervention. There are primary efficacy assessments at Week 2 and Week 4, and a key secondary efficacy assessment at Week 16. Efficacy and safety endpoints will be assessed throughout the entire study. Exploratory endpoints related to hand eczema efficacy will be assessed throughout the study.

Detailed description:

Arms: arm 1: Abrocitinib 200 mg daily through Week 26, plus placebo injections every other week through Week 24 arm 2: Dupilumab 300 mg every other week (2 injections on Day 1) through Week 24, plus placebo tablets daily through Week 26
Interventions: intervention 1: Abrocitinib 200 mg intervention 2: Dupilumab 300 mg
Intervention descriptions: intervention 1: Abrocitinib 200 mg administered as two 100 mg tablets to be taken orally once daily for 26 weeks. Placebo injections will be administered every other week for 24 weeks. intervention 2: Dupilumab 300 mg administered as a single subcutaneous injection every other week for 24 weeks (2 injections on day 1). Placebo tablets will be administered daily.

Protocol documents:
Prot_000.pdf: 
Abrocitinib and Dupilumab
Protocol B7451050
Final Protocol Amendment 2, 14 August 2020
PFIZER CONFIDENTIAL
Page 1
Protocol Title: A PHASE 3B RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, 
ACTIVE CONTROLLED MULTI-CENTER STUDY ASSESSING THE EFFICACY 
AND SAFETY OF ABROCITINIB COMPARED WITH DUPILUMAB IN ADULT 
PARTICIPANTS ON BACKGROUND TOPICAL THERAPY WITH MODERATE 
TO SEVERE ATOPIC DERMATITIS 
Protocol Number: B7451050
Amendment Number: 2
Compound Number: PF-04965842
Study Phase: Phase 3
Short Title: A Study to Assess the Safety and Efficacy of Abrocitinib Compared with 
Dupilumab in Adult Participants with Moderate to Severe Atopic Dermatitis
Acronym: JADE DARE
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
2019-004013-13
Approval Date: 14 August 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
Version Date
Summary and Rationale for Changes
Amendment 2
14-Aug-2020
Study endpoints updated to reflect a more rigorous 
efficacy threshold and the associated statistical methods 
were revised:
EASI-75 in the primary, key secondary and 
secondary endpoints was changed to EASI-90 
to reflect a more rigorous efficacy threshold 
and statistical analysis methods have been 
revised.
EASI-90 in one of the secondary endpoints 
was changed to EASI-75.
Clarified that the estimand is PP-NRS4 
(previously PP-NRS) since the endpoint is 
based on achieving at least a 4-point 
improvement in the severity of PP-NRS4 from 
baseline.
Sample size determination was updated to 
reflect the change from EASI-75 to EASI-90 in 
the primary and key secondary endpoints.
Clarified the CMH analyses method for the 
primary endpoint.
The tipping point analysis was changed to 
multiple imputations under the assumption of 
missing at random.
Per updated safety information, participants with 
increased risk of developing venous thromboembolism 
are excluded.
Inclusion criterion updated to require a clinical 
diagnosis of AD at least 6 months prior to Day 1 instead 
of at least 1 year. The duration of AD diagnosis has not 
been associated with the magnitude of treatment effect 
of other AD therapies. Given other current inclusion 
criteria, such as the requirement for recent 
inadequate response to topical therapies 
and/or treatment with (or consideration for) systemic 
therapies, reducing this inclusion criterion to 6 months 
is not anticipated to affect the study results.
Exclusion of prior use of dupilumab has been expanded 
to include all IL-4 and IL-13 antagonists. Dupilumab is 


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DOCUMENT HISTORY
Document
Version Date
Summary and Rationale for Changes
an IL-4 and IL-13 antagonist and the criterion currently 
only excludes prior dupilumab use. By expanding the 
criterion to include the drug class, we avoid 
inadvertently enriching the patient population with 
participants who are non-responders to this mechanism.
Revised the baseline infection study terminology from 
“viral studies” to “infection studies” to allow for testing 
of other types of microorganisms.
Added additional infection studies sample to be taken at 
each study visit.  This will allow for testing of SARS-
CoV-2 or another emergent microbial organisms.
Language and an appendix were added to address 
COVID-19 and to describe alternative measures to be 
taken during public emergencies. This is in reference to 
the April 2020 PACL.
Added statement that if the participant experiences 
nausea, consideration should be given to administering 
oral study intervention with food. A food effect and 
lower incidence of nausea in a fed state has been 
observed in some participants.
Healthcare Resource Utilization (HCRU) assessment 
was moved from Week 16 to Week 12. There is a 3-
month recall so if you assess at WK12 you are 
capturing the resource use from baseline to WK12 and 
then you capture the rest of the HCRU (more or less) 
when you assess at WK26. If we kept it at WK16 then 
we would miss the first 4 weeks post-baseline.
Added Asthma Control Questionnaire (ACQ) for 
participants with a prior diagnosis of asthma. Asthma is 
a common comorbidity in patients with AD and this 
questionnaire will provide information about whether 
abrocitinib has any effect on asthma control.
New clinical trial data from the abrocitinib study 
B7451013 and from the dupilumab CAFÉ and 
CHRONOS studies have been added to the protocol 
introduction.
Updates made per updated protocol template:
Clarified inclusion criterion 3 for female 
participants.


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DOCUMENT HISTORY
Document
Version Date
Summary and Rationale for Changes
Exploratory objective related to banked 
biospecimens was removed.
Section 8.3 Adverse events and Serious 
Adverse Events
Appendix 3 Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-
up, and Recording.
Appendix 4 Contraceptive Guidance.
Appendix 10 Prohibited concomitant 
medications.
Changes made for improved instruction and process 
clarity:
Requirements for mental health professional 
assessments and recurrent suicidal ideation and 
behavior have been clarified.
The research supporting accelerometry has 
been described.
Added instruction for when to collect the 
eDiaries from participants.
Added instruction to clarify that banked 
biospecimens are collected for all participants 
(as local regulations and IRBs/ECs allow).
Dispensing and administration instructions for 
study intervention have been clarified.
Study-specific definitions of medication errors 
have been updated.
Tuberculosis testing procedures have been 
clarified.
Evaluation of hand eczema has been added to 
the rater qualifications and has been clarified.
Data collection requirements for adverse 
events of conjunctivitis have been added.


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Version Date
Summary and Rationale for Changes
Electronic diary review has been added to the 
Week 24 and Week 26 (EOT/ED) visits.
Clarified that the BSA for a subset of body 
regions (scalp, palms, and soles of feet) 
evaluated in EASI will be entered in the eCRF.
Temporary discontinuation timeframe updated 
for the injectable study intervention and 
requirement added for participants who need 
systemic rescue therapy to temporarily 
discontinue the study intervention while taking 
systemic rescue therapy. Participants need to 
temporarily discontinue the study intervention 
while taking systemic rescue therapy because 
the medications taken together could further 
suppress the participant’s immune system and, 
therefore, cause an increased safety risk.
Clarified that participants who use rescue 
therapy will be defined as “non-responsive” 
after start of rescue therapy.
Added isoniazid as a prohibited concomitant 
medication.
Clarified that the block randomization method 
will be used.
Recall period has been updated for the Medical 
Outcomes Study Sleep Scale (per the December 2019 
PACL).
Anchors have been updated for the Skin Pain Numerical 
Rating Scale (per the December 2019 PACL).
Informal interim analyses for internal decision-making 
have been added.
Collection of prior marijuana use has been removed. 
The information would not be used in analyses.
Country-specific addition for the United Kingdom: Per 
agency requirement, added requirement for sites to 
contact participants who are WOCBP and are not 
entering the long-term extension study (B7451015) at 
12 weeks after the last dose of study intervention to 


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Version Date
Summary and Rationale for Changes
confirm adherence to contraception guidelines per 
protocol.
Country-specific addition for France: Requirements for 
study sites located in France have been added.
References have been updated.
Study acronyms have been updated.
Amendment 1 (Czech 
Republic only)
14-Jul-2020
Country-specific changes for the Czech Republic:
Section 5.2: Patients with increased risk of developing 
venous thromboembolism are excluded. This exclusion 
criterion was added as a result of the updated April 
2020 IB.
Section 6.5.2.: If a participant requires high potency 
topical therapy or systemic rescue therapy, they are to 
be permanently discontinued from the study 
intervention, have an End of Treatment visit and enter 
the 4-week follow-up period. This was a request from 
the Czech Republic.
Section 10.4.: Definition of postmenopausal female was 
revised to specify that the main condition is the absence 
of bleeding for 12 months without an alternative 
medical cause (removed portion of definition that 
allowed for participants age 60 or older to be 
considered postmenopausal). FSH level must be 
assessed in women in the postmenopausal range under 
the age of 60 and not using hormonal contraception or 
HRT (“may” changed to “must”). This was revised per 
the Czech Republic request and to be consistent with 
the current protocol template.
Original Protocol
04 November 2019
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs. 


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................13
1. PROTOCOL SUMMARY...................................................................................................14
1.1. Synopsis ..................................................................................................................14
1.1.1. Estimands....................................................................................................17
1.2. Schema ....................................................................................................................21
1.3. Schedule of Activities (SoA)...................................................................................22
2. INTRODUCTION ...............................................................................................................29
2.1. Study Rationale .......................................................................................................29
2.2. Background .............................................................................................................30
2.2.1. Atopic Dermatitis........................................................................................30
2.2.2. Clinical Efficacy and Safety of Dupilumab in AD.....................................31
2.2.3. Clinical Efficacy and Safety of Abrocitinib in AD ....................................33
2.3. Benefit/Risk Assessment.........................................................................................36
3. OBJECTIVES, ESTIMANDS AND ENDPOINTS ............................................................36
3.1. Estimands ................................................................................................................39
3.2. Adjudication Committee .........................................................................................41
4. STUDY DESIGN.................................................................................................................41
4.1. Overall Design.........................................................................................................41
4.2. Scientific Rationale for Study Design.....................................................................42
4.3. Justification for Dose ..............................................................................................43
4.4. End of Study Definition ..........................................................................................43
5. STUDY POPULATION......................................................................................................44
5.1. Inclusion Criteria.....................................................................................................44
5.2. Exclusion Criteria....................................................................................................46
5.3. Lifestyle Considerations..........................................................................................52
5.3.1. Meals and Dietary Restrictions...................................................................52
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................53
5.3.3. Vaccine and Exposure to Infections Guidelines.........................................53
5.3.3.1. Participant Specific Recommendations.....................................53


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5.3.3.2. Guidance Regarding Household Contact Vaccine-Related 
Exposure............................................................................................53
5.3.4. Surgery........................................................................................................53
5.4. Screen Failures ........................................................................................................54
6. STUDY INTERVENTION..................................................................................................55
6.1. Study Intervention(s) Administered........................................................................55
6.1.1. Administration of Study Interventions .......................................................55
6.1.1.1. Administration of Abrocitinib/Matching Placebo.....................56
6.1.1.2. Administration of Dupilumab/Matching Placebo .....................56
6.1.2. Medical Devices .........................................................................................57
6.2. Preparation/Handling/Storage/Accountability ........................................................57
6.2.1. Preparation and Dispensing........................................................................58
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................59
6.3.1. Allocation to Study Intervention ................................................................59
6.3.2. Breaking the Blind......................................................................................59
6.4. Study Intervention Compliance...............................................................................60
6.4.1. Abrocitinib Compliance..............................................................................61
6.4.2. Dupilumab Compliance..............................................................................61
6.5. Concomitant Therapy..............................................................................................62
6.5.1. Permitted Concomitant Treatments............................................................63
6.5.2. Rescue Therapy for Atopic Dermatitis.......................................................65
6.5.3. Prohibited Medications and Treatments .....................................................66
6.6. Dose Modification...................................................................................................66
6.7. Intervention after the End of the Study...................................................................66
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................67
7.1. Discontinuation of Study Intervention ....................................................................67
7.1.1. Temporary Discontinuation........................................................................67
7.2. Participant Discontinuation/Withdrawal from the Study........................................68
7.2.1. Withdrawal of Consent...............................................................................68
7.3. Lost to Follow up ....................................................................................................69
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................70
8.1. Efficacy Assessments..............................................................................................71


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8.1.1. Rater Qualifications....................................................................................71
8.1.2. Eczema Area and Severity Index (EASI) ...................................................72
8.1.2.1. Body Surface Area – Efficacy (BSA Efficacy).........................74
8.1.3. SCORing Atopic Dermatitis (SCORAD)...................................................74
8.1.4. Investigator’s Global Assessment (IGA) of Atopic Dermatitis..................76
8.1.5. Standardized Background Topical Therapy ...............................................76
8.1.6. Patient-Reported Outcomes (PROs)...........................................................77
8.1.6.1. Peak Pruritus Numerical Rating Scale (PP-NRS).....................77
8.1.6.2. Dermatology Life Quality Index (DLQI)..................................77
8.1.6.3. EuroQuol Quality of Life 5-Dimension 5-Level Scale 
(EQ-5D-5L) .......................................................................................78
8.1.6.4. Healthcare Resource Utilization (HCRU) Questionnaire .........78
8.1.6.5. Patient-Oriented Eczema Measure (POEM) .............................78
8.1.6.6. Hospital Anxiety and Depression Scale (HADS)......................78
8.1.6.7. Medical Outcomes Study (MOS) Sleep Scale ..........................78
8.1.6.8. Skin Pain Numerical Rating Scale (SP-NRS)...........................78
8.1.6.9. Asthma Control Questionnaire (ACQ)......................................78
8.1.7. Exploratory Accelerometry ........................................................................79
8.1.8. Exploratory Assessments of Hand Eczema ................................................80
8.1.8.1. History, Subtype, Clinical Signs, and Extent............................80
8.1.8.2. Investigator’s Global Assessment (IGA) of Hand Eczema.......80
8.2. Safety Assessments .................................................................................................81
8.2.1. Medical History and Physical Examinations..............................................81
8.2.2. Vital Signs ..................................................................................................82
8.2.3. Chest X-Ray................................................................................................82
8.2.4. Electrocardiograms.....................................................................................82
8.2.5. Clinical Safety Laboratory Assessments ....................................................83
8.2.5.1. Hepatitis Testing .......................................................................84
8.2.5.2. Tuberculosis Testing .................................................................85
8.2.6. Infection Studies.........................................................................................85
8.2.7. Suicidal Ideation and Behavior Risk Monitoring.......................................85
8.2.7.1. Columbia Suicide Severity Rating Scale (C-SSRS) .................86


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8.2.7.2. Patient Health Questionnaire – 8 Items (PHQ-8)......................86
8.2.8. Pregnancy Testing ......................................................................................87
8.3. Adverse Events and Serious Adverse Events..........................................................87
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......87
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................88
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF .................88
8.3.2. Method of Detecting AEs and SAEs ..........................................................88
8.3.3. Follow-up of AEs and SAEs.......................................................................89
8.3.4. Regulatory Reporting Requirements for SAEs...........................................89
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................89
8.3.5.1. Exposure During Pregnancy......................................................90
8.3.5.2. Exposure During Breastfeeding ................................................91
8.3.5.3. Occupational Exposure .............................................................92
8.3.6. Cardiovascular and Death Events...............................................................92
8.3.7. Disease-related Events and/or Disease-related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................92
8.3.8. Adverse Events of Special Interest.............................................................92
8.3.8.1. Lack of Efficacy........................................................................92
8.3.9. Medical Device Deficiencies......................................................................92
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........92
8.3.9.2. Follow-up of Medical Device Deficiencies...............................93
8.3.9.3. Prompt Reporting of Device Deficiencies to Sponsor ..............93
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................93
8.3.10. Medication Errors.....................................................................................93
8.4. Treatment of Overdose............................................................................................94
8.5. Pharmacokinetics ....................................................................................................95
8.6. Pharmacodynamics..................................................................................................95
8.7. Genetics...................................................................................................................95
8.7.1. Specified Genetics ......................................................................................95
8.7.2. Banked Biospecimens for Genetics............................................................95
8.8. Biomarkers ..............................................................................................................95


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8.8.1. Specified Gene Expression (RNA) Research .............................................95
8.8.2. Specified Protein Research.........................................................................95
8.8.3. Specified Metabolomic Research ...............................................................95
8.8.4. Banked Biospecimens for Biomarkers .......................................................96
8.9. Medical Resource Utilization and Health Economics.............................................96
9. STATISTICAL CONSIDERATIONS ................................................................................96
9.1. Estimands and Statistical Hypotheses.....................................................................96
9.1.1. Estimands....................................................................................................96
9.2. Sample Size Determination.....................................................................................97
9.3. Populations for Analyses.........................................................................................99
9.4. Statistical Analyses ...............................................................................................100
9.4.1. Efficacy Analyses .....................................................................................100
9.4.2. Type I Error Control Procedure................................................................102
9.4.3. Safety Analyses ........................................................................................102
9.4.4. Other Analyse(s).......................................................................................103
9.5. Interim Analyses ...................................................................................................103
9.5.1. Data Monitoring Committee (DMC)........................................................103
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................104
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............104
10.1.1. Regulatory and Ethical Considerations ..................................................104
10.1.2. Financial Disclosure ...............................................................................105
10.1.3. Informed Consent Process ......................................................................105
10.1.4. Data Protection .......................................................................................106
10.1.5. Committees Structure .............................................................................106
10.1.6. Dissemination of Clinical Study Data ....................................................106
10.1.7. Data Quality Assurance ..........................................................................108
10.1.8. Source Documents..................................................................................109
10.1.9. Study and Site Closure............................................................................109
10.1.10. Publication Policy.................................................................................110
10.1.11. Sponsor’s Qualified Medical Personnel ...............................................110
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................112


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................115
10.3.1. Definition of AE .....................................................................................115
10.3.2. Definition of SAE...................................................................................116
10.3.3. Recording/Reporting and Follow-Up of AE and/or SAE.......................117
10.3.4. Reporting of SAEs..................................................................................120
10.4. Appendix 4: Contraceptive Guidance .................................................................122
10.4.1. Male Participant Reproductive Inclusion Criteria..................................122
10.4.2. Female Participant Reproductive Inclusion Criteria...............................122
10.4.3. Woman of Childbearing Potential ..........................................................122
10.4.4. Contraception Methods...........................................................................123
10.5. Appendix 5: Genetics..........................................................................................125
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......126
10.7. Appendix 7: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................128
10.7.1. Definition of AE and ADE .....................................................................128
10.7.2. Definition of SAE, SADE, and Unanticipated Serious Adverse 
Device Effect .................................................................................................128
10.7.3. Definition of Device Deficiency.............................................................129
10.7.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................130
10.7.5. Reporting of SAEs..................................................................................132
10.7.6. Reporting of SADEs...............................................................................133
10.8. Appendix 8: ECG Findings of Potential Clinical Concern .................................134
10.9. Appendix 9: Diagnostic Criteria for Atopic Dermatitis......................................136
10.10. Appendix 10: Prohibited Concomitant Medications which may result in 
Drug-Drug Interaction (DDI) ..................................................................................137
10.11. Appendix 11: Monitoring and Discontinuation Criteria ...................................139
10.12. Appendix 12: Country-specific Requirements..................................................142
10.12.1. France Contrat Unique..........................................................................142
10.12.2. Czech Republic Country-specific Requirements..................................143
10.12.3. United Kingdom Country-specific Requirements ................................143
10.13. Appendix 13: Alternative Measures During Public Emergencies.....................144


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10.13.1. Telehealth visits....................................................................................144
10.13.2. Home health visits ................................................................................144
10.13.3. Alternative Facilities for Safety Assessments ......................................145
10.13.3.1. Laboratory testing ...............................................................145
10.13.3.2. Electrocardiograms..............................................................146
10.13.4. Study intervention.................................................................................146
10.13.5. Adverse events and serious adverse events ..........................................146
10.13.6. Efficacy assessments ............................................................................146
10.13.7. Data monitoring committee..................................................................147
10.14. Appendix 14: Abbreviations .............................................................................148
11. REFERENCES ................................................................................................................153
LIST OF TABLES
Table 1.
Clinical Sign Severity Scoring Criteria for the Eczema Area and 
Severity Index (EASI) ..............................................................................72
Table 2.
Handprint Determination of Body Surface Area (BSA)...........................73
Table 3.
Eczema Area and Severity Index (EASI) Area Score Criteria.................73
Table 4.
Eczema Area and Severity Index (EASI) Body Region Weighting.........74
Table 5.
Investigator’s Global Assessment (IGA) of Atopic Dermatitis Score......76
Table 6.
Investigator’s Global Assessment (IGA) of Hand Eczema Score............80


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1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Title: A PHASE 3B RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, 
ACTIVE CONTROLLED MULTI-CENTER STUDY ASSESSING THE EFFICACY 
AND SAFETY OF ABROCITINIB COMPARED WITH DUPILUMAB IN ADULT 
PARTICIPANTS ON BACKGROUND TOPICAL THERAPY WITH MODERATE 
TO SEVERE ATOPIC DERMATITIS 
Short Title: A Study to Assess the Safety and Efficacy of Abrocitinib Compared with 
Dupilumab in Adult Participants with Moderate to Severe Atopic Dermatitis
Rationale:
Atopic dermatitis (AD), also known as atopic 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).1,2 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 with a lifetime prevalence of those 
affected in childhood reported to be 34%.3  Earlier reports indicated that, in up to 70% of 
cases, the disease greatly improves or resolves 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 participants 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.4  At every age, 
more than 80% of PEER study participants had symptoms of AD and/or were using 
medication to treat their AD.
Of the currently available therapies, none offers a cure; therefore, the main aims of existing 
treatments are to reduce skin lesions, reduce the occurrence of acute flares, to increase the 
time between relapses, and to reduce pruritus and the resulting sleep disturbance.5,6
Non-medicated topical therapies include emollients.  Medicated topical therapy for moderate 
to severe AD include topical corticosteroids (TCS) (eg, betamethasone, clobetasol, 
fluocinonide), topical calcineurin inhibitors (TCI) (eg, pimecrolimus, tacrolimus), and coal 
tar preparations.  TCS are limited in terms of the treatment duration (eg, corticosteroid use is 
limited to 2 to 4 weeks) and the body region of treatment, due to consistent skin toxicities, as 
well as having risks associated with their broad immunosuppressive actions.  TCI have a 
limited role as a second-line treatment, due to their limitations in the duration and the body 
region of treatment, inhibition of tumor surveillance in the skin, and safety concerns with 
malignancies.  Crisaborole was approved as a medicated topical therapy (phosphodiesterase 4 
[PDE4] inhibitor) in December 2016 by the Food and Drug Administration (FDA) for use 
in patients with mild to moderate AD and is being evaluated for approval in several other 
regions.  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 (eg, corticosteroids, cyclosporine, recombinant interferon 


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gamma (IFN-), mycophenolate mofetil, methotrexate [MTX], azathioprine, intravenous 
immunoglobulin).7
There are a limited number of approved systemic treatments for moderate to severe AD and 
in the US, the only approved systemic drugs are corticosteroids and dupilumab.  Per the 
American Academy of Dermatology (AAD) guidelines, the use of steroids should be avoided 
for the treatment of AD and should be exclusively reserved for acute, severe exacerbations 
and as a short-term bridge therapy to other systemic, steroid-sparing therapies.8
Dupilumab, an injectable human monoclonal antibody targeting interleukin (IL) -4 and -13, 
was approved by the FDA in March 2017 and received marketing authorization in Europe in 
September 2017, for the treatment of moderate to severe AD.  Treatment with systemic 
corticosteroids has known and well documented adverse effects.  Treatment with dupilumab 
has the risk of injection site reactions, allergic reactions, eye and eyelid inflammations and 
cold sores.  Another potential limitation of dupilumab is the possibility for the development 
of antidrug antibodies, which may result in loss of efficacy over time and the development of 
safety concerns such as serum sickness-like reactions.  Furthermore, dupilumab is delivered 
via subcutaneous injection, which may not be a method of administration tolerated well by 
all patients.  During a 1-year, randomized, double-blinded study with dupilumab, in the 
dupilumab 300 mg every 2 weeks (marketed maintenance dose) plus TCS group, the 
estimated difference from placebo of the Investigator's Global Assessment (IGA) response 
rate and Eczema Area and Severity Index (EASI)-75 response rate (≥75% improvement from 
baseline in EASI score) were 26% and 46%, respectively.  The placebo response rate for IGA 
and EASI-75 was 12% and 23%, respectively.9 The dupilumab response rate for a ≥4-point 
improvement from baseline in PP-NRS4 at Week 2 and ≥90% improvement from baseline in 
EASI score (EASI-90) was 18% and 40%, respectively.9  There is a need for therapies for 
those patients who do not respond to dupilumab or who after responding, fail to improve with 
dupilumab. The development of potential treatments with further improvements in efficacy 
remains desirable.
In Europe, cyclosporine is approved for use in patients with severe AD when systemic 
therapy is required.  Cyclosporine use is associated with several undesirable side effects and 
due to its narrow therapeutic index, occasional therapeutic drug monitoring is recommended.  
Known adverse effects include infections, renal toxicity, hepatotoxicity, skin malignancies, 
lymphoma and other malignancies. 
The predominant unmet medical need is for a conveniently administered therapy with an 
acceptable safety profile, for continuous and intermittent use, which is effective for moderate 
to severe AD.  Patients with moderate to severe AD require other systemic treatment options 
beyond those which are currently approved.  Abrocitinib is an oral tablet, providing a more 
convenient route of administration compared with the subcutaneous injection required for 
dupilumab and so it does not have the potential risk of injection site reactions.  Unlike 
dupilumab, abrocitinib is a small molecule and there is no anticipated immunogenicity to 
abrocitinib, and so it is unlikely to generate antidrug antibodies and may be used 
intermittently.


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Key cytokines implicated in the pathophysiology of AD include IL-4,  IL-13, IL-31, and 
IFN-, and require Janus kinase 1 (JAK1) for signal transduction; this suggests that selective 
JAK1 inhibitors that modulate the activity of these cytokines represent a compelling 
approach to the treatment of inflammatory skin diseases such as AD.9   Broader inhibition of 
cytokines, including those important in the pathogenesis of AD, may result in an increased 
proportion of responders, with an acceptable safety profile.
Abrocitinib (formerly known as PF-04965842) 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 for JAK1 when compared, in vitro, against other 
kinases: 28-fold selectivity over Janus kinase 2 (JAK2), >340-fold over Janus kinase 3 
(JAK3) and 43-fold over tyrosine kinase 2 (TYK2), as well as a good selectivity profile over 
the broader range of human kinases.  The selective inhibition of JAK1 will lead to 
modulation of multiple cytokine pathways involved in the pathophysiology of AD, including 
IL-4, IL-13, IL-31 and IFN-.  Data from a Phase 2b proof of concept (POC) study 
(B7451006) that evaluated participants with moderate to severe AD have shown positive 
efficacy with both 100 and 200 mg, as well as an acceptable safety profile, sufficient to 
support further clinical development in a larger Phase 3 program.  
Abrocitinib has been in Phase 3 development since December 2017 treating participants with 
moderate to severe AD with or without topical treatment.  The first Phase 3 studies,
B7451012 and B7451013, that evaluated 100 and 200 mg QD abrocitinib in participants with 
moderate to severe AD, which completed in 2019, reported statistically significant 
improvement in efficacy endpoints in both treatment groups compared to the placebo group, 
with an acceptable safety profile. 
This Phase 3b study will investigate whether abrocitinib provides comparable or improved 
efficacy and safety compared with duplilumab in the treatment of moderate to severe AD.  
Statistical Methods
The objective of the study is to demonstrate superiority of abrocitinib 200 mg once daily 
(QD) to dupilumab 300 mg every other week (Q2W) as measured by Peak Pruritus 
Numerical Rating Scale (PP-NRS4) response at Week 2 and EASI-90 response at Week 4.
Additionally, this study is intended to demonstrate that abrocitinib 200 mg QD is non-inferior 
to dupilumab 300 mg Q2W and if non-inferior, to demonstrate the superiority to dupilumab 
as measured by EASI-90 response at Week 16. A total sample of 600 participants, with 300 
participants randomized to abrocitinib, 300 participants randomized to dupilumab (1:1 
randomization) is planned. The proposed sample size provides adequate power for all 
superiority hypotheses, as follows:

Week 2: this sample size would provide at least 99% power to detect a difference 
assuming a difference of at least 25% in PP-NRS4 between abrocitinib and 
dupilumab and assuming the dupilumab response rate is 11% at Week 2.  


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
Week 4: this sample size will provide approximately 97% power to detect a 
difference assuming a difference of at least 15% in Week 4 EASI-90 between 
abrocitinib and dupilumab and assuming the dupilumab response rate is 12%. 

Week 16: this sample size will provide at least 99% power to show the difference is 
no more than 10% favoring dupilumab in EASI-90 at Week 16 (non-inferiority (NI) 
with a 10% margin), assuming the abrocitinib response rate is 53% and the dupilumab 
response rate is 43% at Week 16. This sample size will also provide approximately 
70% power to demonstrate superiority of abrocitinib 200 mg QD to dupilumab as 
measured by EASI-90 response at Week 16.
The Type I error rate is set at 5% (two sided).  The familywise Type I error rate (for testing 
the primary and key secondary endpoints) will be strongly controlled at 5% using a 
sequential testing approach.  This is described in further detail in Section 9 of the protocol 
and in the statistical analysis plan (SAP).
For analysis of the primary and key secondary endpoints, the Cochran-Mantel-Haenszel test 
adjusted by disease severity group (moderate and severe) will be used.  For participants who 
drop out for any reason or use rescue therapy (Section 6.5.2) at any time during the treatment 
period, the response will be defined as “non-responsive” after that point.
For continuous endpoints, a mixed-effect model with repeated measures (MMRM) will be 
used.  This model will include the factors (fixed effects) for treatment group, disease severity 
group, visit, treatment-by-visit interaction, and relevant baseline value.  Within the 
framework of MMRM, the treatment at each time point will be derived from the MMRM 
model.
All participants who receive study intervention (safety population) will be included in the 
safety analyses.  All the safety data will be summarized descriptively through appropriate 
data tabulations, descriptive statistics, categorical summaries, and graphical presentations.
Objectives, Estimands and Endpoints
1.1.1. Estimands
There are 2 estimands for the study.
Estimand 1, composite estimand:

Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population; 

Variable: response based on achieving at least a 4-point improvement in the severity 
of the PP-NRS4 from baseline at Week 2; for participants who drop out for any 
reason or use rescue therapy (Section 6.5.2) at any time during the treatment period, 
the response will be defined as “non-responsive” after that point;


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•
Interventional effect: Effect of randomized treatment accounting for treatment 
adherence, rescue therapy, and response; the intercurrent event (drop-out or use of 
rescue therapy) is captured through the variable definition;
•
Population-level summary: differences in proportions of responders between
abrocitinib and dupilumab.
Estimand 1 composite estimand is the primary estimand for the primary and key secondary 
endpoints: PP-NRS4 response at Week 2, EASI-90 at Week 4, and EASI-90 at Week 16.  
Other binary outcome measures such as response based on PP-NRS4 and EASI-90 at all 
other scheduled timepoints, EASI-75, and IGA, will follow the same structure.
Estimand 2, hypothetical estimand:  
•
Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population;  
•
Variable: Percent change from baseline in SCORing Atopic Dermatitis (SCORAD) at 
all scheduled timepoints;
•
Interventional effect: Effect of randomized treatment as if all participants maintain 
their randomized treatment; drop-out for any reason and use of rescue therapy are the 
intercurrent events; data after dropout or use of rescue therapy at any time during the 
treatment period will be censored;
•
Population-level summary: Difference in least-square means between abrocitinib and 
dupilumab.
•
Percent change from baseline or change from baseline to each specific post baseline 
scheduled time points in a continuous outcome measure such as the Hospital Anxiety 
and Depression Scale (HADS), Patient-Oriented Eczema Measure (POEM), 
Dermatology Life Quality Index (DLQI), and EuroQol Quality of Life 5-Dimension 
5-Level Scale (EQ-5D-5L) will follow the same structure as defined for SCORAD.
Primary Objectives
Primary Endpoints
To compare the efficacy of abrocitinib 
200 mg once daily (QD) versus dupilumab 
(as per label guidelines) in adult participants 
on background topical therapy with 
moderate to severe atopic dermatitis (AD).
- Response based on achieving at least a 4-
point improvement in the severity of Peak 
Pruritus Numerical Rating Scale (PP-NRS4) 
from baseline at Week 2.
- Response based on achieving the Eczema 
Area and Severity Index (EASI)-90 (ı90% 
improvement from baseline) at Week 4.
Key Secondary


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Page 19
To compare the efficacy of abrocitinib 200 
mg once daily versus dupilumab on 
additional efficacy endpoints in adult 
participants on background topical therapy 
with moderate to severe atopic dermatitis 
(AD).
- Response based on achieving the Eczema 
Area and Severity Index (EASI)-90 (ı90% 
improvement from baseline) at Week 16.
Overall Design:
This is a randomized, double-blind, double-dummy, active controlled, multi-center study to 
assess the efficacy and safety of abrocitinib 200 mg QD compared with dupilumab 
(administered per label guidelines) in adult participants on background topical therapy, with 
moderate to severe AD.  The treatment duration is 26 weeks.  A total of approximately 
600 participants will be enrolled from approximately 220 sites globally.  There are primary 
efficacy assessments at Week 2 and Week 4, and a key secondary efficacy assessment at 
Week 16.  Efficacy and safety endpoints will be assessed throughout the entire study.  
Participants who complete the study through the Week 26 visit and are deemed eligible may 
enter the long-term extension (LTE) Study B7451015.  A study design schematic is presented 
in Section 1.2.
After providing informed consent, participants will be assessed for study eligibility at the 
screening visit.  Participants will undergo screening within approximately 28 days prior to 
randomization.  Use of screening procedures exceeding 28 days prior to randomization 
should be discussed with the Pfizer Medical Monitor.  
During the screening period, systemic treatments for AD will be washed out, as applicable, 
according to eligibility requirements.  Eligible participants must have a documented history, 
within 6 months of the screening visit, of inadequate response to treatment with medicated 
topical therapy for at least 4 weeks or must have required systemic therapies for control of 
their disease within the previous year.  Eligible participants must meet the eligibility criteria, 
which includes being dupilumab naïve, at baseline.  
In addition, participants must be willing and able to use standardized background topical 
therapy, as per protocol guidelines, throughout the duration of the study. After Week 4, if 
medically necessary, participants with intolerable AD symptoms may receive locally-
approved rescue therapy, at the investigator’s discretion, pursuant to the protocol guidelines 
(refer to Section 6.5.2).
Participants may be re-screened once if they fail the screening evaluation for reasons related 
to incidental transitory conditions.  Participants 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.


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Participants who continue to meet eligibility criteria at baseline will undergo Day 1 
assessments and be randomized in a 1:1 ratio to receive abrocitinib 200 mg QD with 
dupilumab-matching placebo administered every other week or dupilumab 300 mg 
administered every other week (with a loading dose of 600 mg at baseline) with 
abrocitinib-matching placebo administered QD.  Investigators, participants, and the sponsor 
study team will be blinded to treatment group assignment.
The total treatment period is 26 weeks.  Participants discontinuing early from treatment, or 
who are otherwise ineligible for the LTE study, will undergo a 4-week follow-up period (See 
Section 10.12.3 for UK country-specific requirements).
Disclosure Statement:
This is a Parallel Treatment study with 2 Arms that are double-blind, double-dummy.
Number of Participants:
Approximately 600 participants will be randomly assigned to study intervention. 
Intervention Groups and Duration:

Abrocitinib 200 mg (2 x 100 mg tablets) administered orally QD and 
dupilumab-matching placebo administered by subcutaneous injection every other 
week (2 injections at baseline; to dummy the loading dose) from Day 1 to Week 26 
(the last injection of dupilumab-matching placebo will occur at Week 24).

Dupilumab 300 mg administered by subcutaneous injection every other week (with a 
loading dose of 600 mg at baseline) and abrocitinib-matching placebo administered 
orally QD from Day 1 to Week 26 (the last injection of dupilumab will occur at Week 
24).
Data Monitoring Committee: Yes


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Page 21
1.2. Schema


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1.3. Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the relevant noted sections of the protocol for 
detailed information on each procedure and assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Enrollment
Informed consent
X
Refer to Section 10.1.3 in Appendix 1.
Register participant in 
IRT system
X
Inclusion/Exclusion 
Criteria
X
X
Refer to Section 5.1 and Section 5.2 for 
Inclusion and Exclusion Criteria, 
respectively.
Demographics: Medical, 
Tobacco, Alcohol, and 
Atopic Dermatitis (AD) 
Disease Histories
X
Any previous history of 
intolerance/allergy to any drug, 
regardless of indication. AD disease 
history includes collection of AD 
diagnosis and duration
Review 
Prior/Concomitant 
Medications & 
Treatments
X
X
X
X
X
X
X
X
X
X
X
X


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Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Dispense eDiary and 
instruct participants on 
use
X
Train/check 
understanding of 
participants on protocol 
guidance for
background medicated 
and non-medicated
topical therapy and 
daily recording in 
eDiary
X
X
X
X
X
X
X
X
X
X
Refer to Section 6.5.1.
Collect eDiary
X
X
Collect the eDiary at Week 26/EOT for 
participants who rollover into the 
B7451015 long-term extension study.
Collect the eDiary from all other 
participants at Week 30/EOS (or at the 
last visit a participant will have if ED).
Provide Participant 
Emergency Contact 
Card
X
Medical Procedures
Complete Physical 
Exam
X
X
X
Refer to Section 8.2.1  
Targeted Physical Exam
X
X
X
X
X
X
X
Refer to Section 8.2.1
Vital Signs
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.2.2.  Temperature 
does not need to be recorded at the 
Week 8 visit.
Weight
X
Refer to Section 8.2.1
Height
X
X
X
X
Refer to Section 8.2.1
Chest X-ray
X
Refer to Section 8.2.3.


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Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
ECG (12-lead)
X
X
X
X
Refer to Section 8.2.4.
Laboratory Assessments 
Refer to Section 8.2.5 and Appendix 2 for more information on clinical safety laboratory assessments.
Serum Chemistry and 
Hematology (including 
Coagulation Panel and 
additional sample for 
infection studies) 
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.2.6 for the infection 
studies and Appendix 2 for all tests
Lipid Panel
X
X
X
X
X
X
X
8-hour fast required.
High-sensitivity 
C-Reactive Protein 
(hsCRP) 
X
X
X
X
X
X
X
X
X
X
This assessment will be blinded after 
the screening visit.
Urinalysis
X
X
X
X
X
X
X
X
X
X
Serum FSH or 
Pregnancy Test 
X
Serum pregnancy testing at screening is 
required for WOCBP.  FSH test to be 
performed at screening to confirm 
postmenopausal status in female 
participants who have been 
amenorrhoeic for at least 12 months.
Urine Pregnancy Test 
(conducted at study site) 
X
X
X
X
X
X
X
X
X
This test must be performed prior to 
dosing with study intervention for 
WOCBP.
HIV Testing
X
Will be performed for all participants; 
those who screen positive will be 
excluded from the study.
HBV and HCV 
Testing
X
Refer to Section 8.2.5.1
HBV DNA reflex 
testing 
X
X
X
Refer to Appendix 2 and 
Section 8.2.5.1.


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Page 25
Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Tuberculosis Test
X
A documented TB test performed 
within 12 weeks prior to Day 1 (Week 
0) is acceptable.  Refer to Appendix 2  
and Section 8.2.5.2.
Lymphocyte Subsets
X
X
X
X
X
X
X
X
X
Serum Sample for 
Baseline Infection Study
X
Refer to Section 8.2.6. and Appendix 2
Study Intervention Administration (NOTE: should occur at the end of the site visit where applicable).
Randomization 
X
Oral Drug Dispensing
X
X
X
X
X
X
Refer to Section 6.1.1.1
Injectable Drug 
Dispensing
X
X
X
X
X
X
X
Refer to Section 6.1.1.2
Study Intervention 
Accountability  
X
X
X
X
X
X
X
Participant Injection 
Training
X
Refer to Section 6.1.1.2
Observed Study 
Intervention 
Administration
X
X
X
X
X
X
X
Refer to Section 6.1.1.2
Review eDiary to assess 
completion
X
X
X
X
X
X
X
X
X
X
Assess eligibility for 
B7451015
X
Participants who complete the Week 26 
visit will be assessed for eligibility for 
participation in the long-term extension 
study B7451015.
Atopic Dermatitis Clinical Assessments 
Eczema Area and 
Severity Index (EASI)
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.1.2


Abrocitinib and Dupilumab
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Page 26
Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Body Surface Area 
(BSA from EASI) 
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.1.2.1
SCORing Atopic 
Dermatitis (SCORAD)
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.1.3
Investigator’s Global 
Assessment (IGA) 
X
X
X
X
X
X
X
X
X
X
Refer to Section 8.1.4
Patient-reported Outcomes
Peak Pruritus Numerical 
Rating Scale (PP-NRS)
X-------X
→
→
→
→
→
→
→
→
→
→
X
Refer to Section 8.1.6.1.  PROs must 
be completed before all other clinical 
assessments.
Dermatology Life 
Quality Index (DLQI)
X
X
X
X
X
X
X
Refer to Section 8.1.6.2
EQ-5D-5L
X
X
X
X
X
Refer to Section 8.1.6.3
Healthcare Resource 
Utilization (HCRU)
X
X
X
Refer to Section 8.1.6.4
Patient-Oriented 
Eczema Measure 
(POEM)
X
X
X
X
Refer to Section 8.1.6.5
Hospital Anxiety and 
Depression Scale 
(HADS)
X
X
X
X
Refer to Section 8.1.6.6
Medical Outcomes 
Study (MOS) Sleep 
Scale
X
X
X
X
Refer to Section 8.1.6.7
Skin Pain NRS
X
X
X
X
X
X
Refer to Section 8.1.6.8
Asthma Control 
Questionnaire (ACQ)
X
X
X
X
Refer to Section 8.1.6.9. Given to all 
participants with a prior diagnosis of 
asthma.


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Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Optional Accelerometry
Accelerometry 
training/retraining
X
X
X
X
X
X
X
X
Refer to Section 8.1.7
Issue/collect 
accelerometry devices
X
X
X
X
X
X
X
Night Time Itch 
Accelerometry
X--------X
X-----------------X
X
X
X
X
Hand Eczema Clinical Assessments
History, subtype, 
clinical signs and extent
X
Refer to Section 8.1.8.
Investigator’s global 
assessment (IGA)
X
X
X
X
X
X
X
X
X
X
Safety
C-SSRS
X
X
X
X
X
X
X
X
Refer to Section 8.2.7.1
PHQ-8
X
Refer to Section 8.2.7.2
Serious and non-serious 
adverse event 
monitoring
X
X
X
X
X
X
X
X
X
X
X
X
Refer to Appendix 3.
Contraception Check
X
X
X
X
X
X
X
X
X
X
X
X
Refer to Appendix 4 for contraceptive 
guidance.
Banked Biospecimens
Banked Biospecimen 
for Genetics
X
Required to be collected for all 
participants (as local regulations and 
IRBs/ECs allow).
Collect a 2 mL blood sample optimized 
for DNA isolation (Prep D1.5).  Refer 
to Section 8.7.2.


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Procedure
Screening
Study Intervention Period
EOT / 
ED 
Visit
EOS 
Follow-up
Visit (4 
weeks after 
ED/EOT)
Notes
Visit
1
2
3
4
5
6
7
8
9
10
11
12
Study Day
D1
D8
D15
D29
D57
D85
D113
D141
D169
D183
D211
Study Week
WK0 WK1
Call
WK2 WK4 WK8 WK12 WK16 WK20 WK24
Call
WK26
WK30
Visit Window (Days)
-28
0
1 
1
2
3 
3
3
3
3
3
3
Banked Biospecimens 
for Biomarkers
X
X
Required to be collected for all 
participants (as local regulations and 
IRBs/ECs allow).
Collect 4 mL blood sample optimized 
for biomarkers (Prep B2.5) and isolate 
serum.
Collect a 2.5 mL blood sample 
optimized for RNA isolation (Prep R1). 
Refer to Section 8.8.4.
Abbreviations: → = completed daily; Ab = antibody; ACQ = Asthma Control Questionnaire; BSA = body surface area; C-SSRS = Columbia Suicide Severity Rating Scale; 
DLQI = Dermatology Life Quality Index; DNA = deoxyribonucleic acid; D=Day; EASI = Eczema Area and Severity Index; ECG = electrocardiogram; EOS=End of Study; EOT 
= End of Treatment; ED= early discontinuation; EQ-5D-5L = EuroQol Quality of Life 5-Dimension 5-Level Scale; FSH = follicle stimulating hormone; HADS= Hospital Anxiety 
and Depression Scale; HBsAg = hepatitis B surface antigen; HBsAb = hepatitis B surface antibody; HBcAb = hepatitis B core antibody; HBV =hepatis b virus; HCRU = 
Healthcare Resource Utilization; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hsCRP = high-sensitivity C-Reactive Protein; IGA = Investigator’s Global 
Assessment; IRT = Interactive Response Technology; LLQ = lower limit quantification; PHQ-8 = Patient Health Questionnaire 8 items; PP-NRS = Peak Pruritus Numerical 
Rating Scale; POEM = Patient-Oriented Eczema Measure;  PRO = Patient Reported Outcome; RNA = Ribonucleic acid; SCORAD = SCORing Atopic Dermatitis; WK=Week; 
WOCBP = women of childbearing potential.


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2. INTRODUCTION
Dupilumab, an injectable human monoclonal antibody targeting IL-4 and -13, was first 
approved in the US and EU (European Union) in 2017 for the treatment of moderate to 
severe AD.  
Abrocitinib (formerly known as PF-04965842) 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 broader range of human kinases.  The selective inhibition of JAK1 will lead 
to modulation of multiple cytokine pathways involved in the pathophysiology of AD, 
including IL-4, IL-13, IL-31 and IFN-.  Abrocitinib is being developed as an oral treatment 
for patients with moderate to severe AD based on the existing unmet need in AD, its novel 
mechanism of action, and the clinical results obtained in Phase 1 and Phase 2 studies.  The 
clinical development program for abrocitinib includes healthy volunteers, participants with 
psoriasis and participants with AD.
Data from a Phase 2b POC study (B7451006) that evaluated participants with moderate to 
severe AD have shown positive efficacy with both 100 and 200 mg, as well as an acceptable 
safety profile, sufficient to support further clinical development in a larger Phase 3 program.
2.1. Study Rationale
Atopic dermatitis (AD), also known as atopic 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 US.1,2  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 with a lifetime prevalence of those affected in 
childhood reported to be 34%.3  Earlier reports indicated that, in up to 70% of cases, the 
disease greatly improves or resolves 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 participants enrolled in the 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.4 At every age, more than 80% of PEER study participants 
had symptoms of AD and/or were using medication to treat their AD.  In 833 AD participants 
who were aged 20 years or older when they visited the clinic and 45 years or older when they 
responded to a follow-up questionnaire, 59% responded that they had defined persistent AD 
at some time during the last 12 months.10
Of the currently available therapies, none offers a cure; therefore, the main aims of existing 
treatments are to improve skin lesions, to reduce the occurrence of acute flares, to increase 
the time between relapses, and to reduce pruritus and the resulting sleep disturbance.5,6
Non-medicated topical therapies include emollients.  Medicated topical therapy for moderate 
to severe AD include TCS (eg, betamethasone, clobetasol, fluocinonide), TCI (eg, 


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pimecrolimus, tacrolimus), and coal tar preparations.  TCS are limited in terms of the 
treatment duration (eg, corticosteroid use is limited to 2 to 4 weeks) and the body region of 
treatment, due to consistent skin toxicities, as well as having risks associated with their broad 
immunosuppressive actions.  TCI have a limited role as a second-line treatment, due to their 
limitations in the duration and the body region of treatment, inhibition of tumor surveillance 
in the skin, and safety concerns with malignancies.  Crisaborole was approved as a medicated 
topical therapy (PDE4 inhibitor) in December 2016 by the FDA for use in patients with mild 
to moderate AD and is being evaluated for approval in several other regions.  Additional 
treatments generally reserved for severe AD include phototherapy (eg, UVA with or without 
psoralen, UVB narrowband or broadband) and systemic agents (eg, corticosteroids, 
cyclosporine, recombinant interferon gamma (IFN-), mycophenolate mofetil, methotrexate 
[MTX], azathioprine, intravenous immunoglobulin).7
There are a limited number of approved systemic treatments for moderate to severe AD and 
in the US, the only approved systemic drugs are corticosteroids and dupilumab.  Per the 
American Academy of Dermatology (AAD) guidelines, the use of steroids should be avoided 
for the treatment of AD and should be exclusively reserved for acute, severe exacerbations 
and as a short-term bridge therapy to other systemic, steroid-sparing therapies.8
The predominant unmet medical need is for a conveniently administered therapy with an 
acceptable safety profile, for long-term use, which is effective for moderate to severe AD.  
Patients with moderate to severe AD require other systemic treatment options beyond those 
which are currently approved. 
2.2. Background
2.2.1. Atopic Dermatitis
The majority of AD studies conducted across multiple age groups suggest decreasing 
prevalence with older age.11 Adult-onset AD does occur, though it is less common.  The 
prevalence of AD in adults is estimated to be 10%.12 Recent studies have indicated that adults 
with AD are more likely to smoke cigarettes, drink alcohol, and have a sedentary lifestyle, 
potentially associated with increased comorbidities, such as asthma and cardiovascular 
disease.13
Although great strides have been made in understanding the causes, 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, allergic responses,
defective antimicrobial immune defense, and a genetic predisposition.  The predominant 
symptom 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
Acute AD lesions have been associated with the type 2 helper T cell (TH2) phenotype, 
showing dominance of IL-4, -5, -13, and -31 secretion.9,14,15 Recent research showed that a 


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small increase of type 1 helper T cell (TH1) associated genes has also been detected in the 
acute phase.16
While IL-4-producing TH2 cells may drive the development of atopic skin lesions, chronic 
lesions show either the coexistence of both IL-4-producing TH2 and IFN--producing TH1 
cells or TH1 dominance.14  This coexistence of TH2 and TH1 responses or TH1 dominance 
is more likely to be the underlying immunopathology in adult patients who have had AD 
chronically or intermittently since childhood.  Recent evidence also supports IL-31’s role in 
pruritus and inflammation in AD.9,15
In Europe, cyclosporine is approved for use in patients with severe AD when systemic 
therapy is required.  Cyclosporine use is associated with several undesirable side effects and 
due to its narrow therapeutic index, occasional therapeutic drug monitoring is recommended.  
Known adverse effects include infections, renal toxicity, hepatotoxicity, skin malignancies, 
lymphoma and other malignancies. 
2.2.2. Clinical Efficacy and Safety of Dupilumab in AD
Dupilumab, an injectable human monoclonal antibody targeting interleukin (IL) -4 and -13, 
was approved by the FDA in March 2017 and received marketing authorization in Europe in 
September 2017, for the treatment of moderate to severe AD.  Treatment with systemic 
corticosteroids has known and well documented adverse effects.
During a 1 year, randomized, double blinded study with dupilumab, in the dupilumab 300 mg 
every 2 weeks (marketed maintenance dose) plus TCS group, the estimated difference from 
placebo of the Investigator's Global Assessment (IGA) response rate and Eczema Area and 
Severity Index (EASI) 75 response rate (≥75% improvement from baseline in EASI score) 
were 26% and 46%, respectively.  The placebo response rate for IGA and EASI-75 was 12% 
and 23%, respectively. The dupilumab response rate for a ≥4-point improvement from 
baseline in PP-NRS4 at Week 2 and ≥90% improvement from baseline in EASI score (EASI-
90) was 18% and 40%, respectively.9  There is a need for therapies for those patients who do 
not respond to dupilumab or who after responding, fail to improve with dupilumab. The 
development of potential treatments with further improvements in efficacy remains desirable.
In 2 randomized, placebo-controlled, Phase 3 trials of identical design (SOLO 1 and SOLO 
2), adults with moderate-to-severe atopic dermatitis whose disease was inadequately 
controlled by topical treatment were enrolled. Participants were randomly assigned in a 1:1:1 
ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the 
same dose of dupilumab every other week alternating with placebo. The primary outcome 
was the proportion of participants who had both a score of 0 or 1 (clear or almost clear) on 
the Investigator’s Global Assessment and a reduction of 2 points or more in that score from 
baseline at week 16.  In SOLO 1 (671 participants), the primary outcome occurred in 85 
participants (38%) who received dupilumab every other week and in 83 (37%) who received 
dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both 
comparisons with placebo). The results were similar in SOLO 2 (708 participants), with the 
primary outcome occurring in 84 participants (36%) who received dupilumab every other 
week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who 


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received placebo (P<0.001 for both comparisons). In addition, in the 2 trials, an improvement 
from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was 
reported in significantly more participants who received each regimen of dupilumab than in 
participants who received placebo (P<0.001 for all comparisons). Dupilumab was also 
associated with improvement in other clinical end points, including reduction in pruritus and 
symptoms of anxiety or depression and improvement in quality of life. Injection-site 
reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo 
groups.17
In the CAFÉ study, the efficacy and safety of dupilumab in combination TCS was evaluated 
in 325 adults with inadequate response to/intolerance of cyclosporin A (CsA), or for whom 
CsA treatment was not medically advisable.  In this 16-week, double-blind, randomized, 
placebo-controlled, Phase 3 trial, participants were randomized 1:1:1 to subcutaneous 
dupilumab 300 mg weekly (QW) or every 2 weeks (Q2W) or placebo. All received 
concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered 
if lesions cleared or could be stopped for adverse reactions to TCS.  Significantly more 
participants in the dupilumab QW + TCS and Q2W + TCS groups achieved ≥ 75% 
improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the 
placebo + TCS group (primary endpoint) (59.1% and 62.6% vs. 29.6%, respectively; P < 
0·001 vs. placebo + TCS, both doses). More participants in the dupilumab QW + TCS and 
Q2W + TCS groups achieved ≥ 90% improvement from baseline in the EASI at Week 16 vs. 
the placebo + TCS group (post-hoc outcome) (37.3% and 45.8% vs. 12.0%, respectively). 
Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the 
dupilumab QW + TCS and Q2W + TCS groups, including pruritus, pain, sleep disturbance, 
symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar 
overall rates of adverse events (QW + TCS, Q2W + TCS and placebo + TCS groups: 69.1%, 
72.0% and 69.4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, 
respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were 
more frequent with placebo + TCS.18
In the CHRONOS study, the long-term efficacy and safety of dupilumab with medium-
potency topical corticosteroids versus placebo with topical corticosteroids was evaluated in 
740 adults with moderate-to-severe atopic dermatitis.  Participants were randomly assigned 
(3:1:3) to subcutaneous dupilumab 300 mg QW, dupilumab 300 mg Q2W, or placebo.  At 
Week 16, more participants who received dupilumab plus topical corticosteroids achieved the 
coprimary endpoints of IGA 0/1 (39% [125 participants] who received dupilumab plus 
topical corticosteroids QW and 39% [41 participants] who received dupilumab Q2W plus 
topical corticosteroids vs 12% [39 participants] who received placebo plus topical 
corticosteroids; p<0·0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0·0001). 
Week 52 results were similar. Adverse events were reported in 261 (83%) participants who 
received dupilumab qw plus topical corticosteroids, 97 (88%) participants who received 
dupilumab Q2W, and 266 (84%) participants who received placebo, and serious adverse 
events in 9 (3%), 4 (4%), and 16 (5%) participants, respectively. No significant dupilumab-
induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were 
more common in participants treated with dupilumab plus topical corticosteroids than in 
participants treated with placebo plus topical corticosteroids.9


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Treatment with systemic corticosteroids has known and well documented adverse effects.  
Treatment with dupilumab has the risk of injection site reactions, allergic reactions, eye and 
eyelid inflammation and cold sores.  Another potential limitation of dupilumab is the 
possibility for development of antidrug antibodies, which may result in loss of efficacy over 
time and the development of safety concerns such as serum sickness-like reactions.  
Furthermore, dupilumab is delivered via subcutaneous injection, which may not be a method 
of administration tolerated well by all participants.20
2.2.3. Clinical Efficacy and Safety of Abrocitinib in AD
Abrocitinib is being developed as an oral treatment for participants with moderate to severe 
AD based on the existing unmet need in AD, its novel mechanism of action, and the clinical 
results obtained in Phase 1, Phase 2, and Phase 3 studies.  The clinical development program 
for abrocitinib includes healthy participants, as well as participants with psoriasis and with 
AD.
Abrocitinib is an oral tablet, providing a more convenient route of administration compared 
with the subcutaneous injection required for dupilumab and so it does not have the potential 
risk of injection site reactions.  Unlike dupilumab, abrocitinib is a small molecule and there is 
no anticipated immunogenicity to abrocitinib, and so it is unlikely to generate antidrug 
antibodies and may be used intermittently.
Key cytokines implicated in the pathophysiology of AD include IL-4, IL-5, IL-13, IL-31, and 
IFN-, and require Janus kinase 1 (JAK1) for signal transduction; this suggests that selective 
JAK1 inhibitors that modulate the activity of these cytokines represent a compelling 
approach to the treatment of inflammatory skin diseases such as AD.9 Broader inhibition of 
cytokines, including those important in the pathogenesis of AD, may result in an increased 
proportion of responders, with an acceptable safety profile.
B7451006 was a Phase 2b POC trial in 269 adults (ages 18-75) with moderate to severe AD 
investigating doses of abrocitinib at doses of 10, 30, 100, and 200 mg or placebo taken once 
daily for up to 12 weeks.  The primary endpoint in this study was the proportion of 
participants achieving an 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 abrocitinib 100 mg and 200 mg dose groups were 
significantly greater than placebo in participants with moderate to severe AD.  The IGA 
response rates of the 200 mg and 100 mg groups were 44.5% and 27.8%, respectively.  The 
IGA response rate in the placebo group was 6.3% and 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 (% CFB) in EASI scores at Week 12 were significantly 
higher for both the 200 mg and 100 mg groups compared to placebo.  The estimated percent 
change from baseline in EASI score was -35.2% in the placebo group, -82.6% in the 200 mg 
group and -59.0% in the 100 mg group.  At Week 12, the proportion of participants achieving 


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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.  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.  
At Day 15, the proportion of response based on achieving at least a 4-point improvement in 
the severity of PP-NRS from baseline of abrocitinib 100 mg and 200 mg dose groups was 
greater than placebo.  The estimated proportion of PP-NRS 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.  Response rates at Week 12 for the 10 mg and 30 mg groups were not 
significantly different from placebo.  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 (PP-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 PP-NRS score).
Abrocitinib appeared generally safe and well tolerated in this study.  Overall, adverse events 
(AE)s and serious adverse events (SAE)s 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 (SOC), and the majority of the AEs were mild.  
There were 2 cases of herpes zoster, 1 in the 10 mg group (not treatment related), and 1 in the 
30 mg group (treatment related).  There were dose-dependent decreases in platelet counts 
observed in the study, with a return towards baseline after Week 4.
Further details of the clinical development program can be found in the Investigator’s 
Brochure (IB).
Abrocitinib has been in Phase 3 development since December 2017 treating participants with 
moderate to severe AD with or without topical treatment.  The first Phase 3 studies,
B7451012 and B7451013, that evaluated 100 and 200 mg QD abrocitinib in participants with 
moderate to severe AD, which completed in 2019, reported statistically significant 
improvement in efficacy endpoints in both treatment groups compared to the placebo group, 
with an acceptable safety profile. 
B7451012 and B7451013 were replicate randomized, double-blind, placebo-controlled, 
parallel-group, Phase 3 studies which evaluated the efficacy and safety of abrocitinib 
monotherapy in 387 and 391 participants, respectively, aged 12 years and older, with 
moderate to severe AD. The treatment duration for both studies was 12 weeks. Eligible 
participants were randomized in a 2:2:1 ratio to receive abrocitinib 200 mg or 100 mg QD or 
matching placebo. Randomization was stratified by baseline disease severity (moderate 
[IGA=3] and severe [IGA=4] AD) and age (age <18 and ≥18 years).


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The co-primary efficacy endpoints were response based on the IGA score of clear (0) or 
almost clear (1) and a reduction from baseline of ≥2 points at Week 12 and response based 
on ≥75% improvement from baseline in EASI score (EASI-75) at Week 12. The key 
secondary efficacy endpoints were response based on ≥4 points improvement from baseline 
in the peak pruritus NRS (PP-NRS) for severity at Weeks 2, 4, and 12 and change from 
baseline in PSAAD at Week 12.
Both studies met both co-primary endpoints. Specifically, abrocitinib 200 mg QD was 
superior to placebo at Week 12 for both IGA and EASI-75 responses. 

In B7451012, IGA response rate was 43.8% in the 200 mg QD arm and 7.9% for the 
placebo arm. The EASI-75 response rate was 62.7% in the 200 mg QD arm and 
11.8% for the placebo arm. The treatment difference (95% confidence interval [CI]) 
for IGA was 36% (26.2, 45.7), p<0.0001 and that for EASI-75 was 51% (40.5, 61.5), 
p<0.0001.
At Week 12, abrocitinib 100 mg QD was also superior to placebo for both IGA and 
EASI-75 responses. The IGA and EASI-75 response rates were 23.7% and 39.7%, 
respectively, in the 100 mg QD arm. The treatment difference (95% CI) for IGA was 
15.8% (6.8, 24.8), p=0.0037 and that for EASI-75 was 27.9% (17.4, 38.3), p<0.0001. 

In B7451013, the IGA response rate was 38.1% in the 200 mg QD arm and 9.1% for 
the placebo arm. The EASI-75 response rate was 61.0% in the 200 mg QD arm and 
10.4% for the placebo arm. The treatment difference (95% CI) for IGA was 28.7% 
(18.6, 38.8), p<0.0001 and that for EASI-75 was 50.5% (40.0, 60.9), p<0.0001.
At Week 12, abrocitinib 100 mg QD was also superior to placebo for both IGA and 
EASI-75 responses. The IGA and EASI-75 response rates were 28.4% and 44.5%, 
respectively, in the 100 mg QD arm. The treatment difference (95% CI) for IGA was 
19.3% (9.6, 29.0), p=0.0008 and that for EASI-75 was 33.9% (23.3, 44.4), p<0.0001. 
In addition, the treatment difference for abrocitinib 200 mg QD relative to abrocitinib 
100 mg QD was 9.7% (-0.7, 20.0) for IGA and 16.5% (5.6, 27.4) for EASI-75 at 
Week 12.
Both studies met both the key secondary endpoints. Both abrocitinib doses showed 
statistically significant separation from placebo in response rates at all visits after baseline. In 
addition, response rates in the 200 mg QD arm were consistently higher than in the 100 mg 
QD arm.
Change from baseline in the total PSAAD score at Week 12 was statistically significant for 
both abrocitinib doses relative to placebo. In addition, the change from baseline in the 200 
mg QD arm was greater in magnitude than in the 100 mg QD arm.
Safety results in both studies show that both doses of abrocitinib were well-tolerated, and 
there were no unexpected safety events. The proportion of participants experiencing adverse 
events was higher in the abrocitinib group compared with the placebo group. The proportion 
of participants experiencing serious adverse events (SAEs) and severe adverse events was 


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similar across all treatment arms. The discontinuation rates due to an adverse event were low 
in each treatment arm compared to placebo.
This Phase 3b study will investigate whether abrocitinib provides comparable or improved 
efficacy and safety compared with duplilumab in the treatment of moderate to severe AD.  
2.3. Benefit/Risk Assessment
There was clinically meaningful benefit demonstrated with abrocitinib in the Phase 2b POC 
study in adult participants with moderate to severe AD and the completed Phase 3 studies 
B7451012 and B7451013.  The potential risks of treatment include those that were noted in 
Phase 2b and Phase 3 studies and those based on the pharmacology of Janus kinase (JAK) 
inhibitors and include viral reactivation, serious and opportunistic infections, hematopoietic 
effects (including reduced platelet count), and malignancy and immunoproliferative 
disorders.  The most common events were gastrointestinal disorders, nervous system 
disorders, and skin/subcutaneous tissue disorders.  In Study B7451001, 2 participants 
discontinued from the study due to AEs.  One participant in the abrocitinib 100 mg group 
discontinued due to an AE of second-degree atrioventricular block, which was considered as 
non-treatment-related and was attributed to a pre-existing condition by the investigator.  
Appropriate risk evaluation and mitigation strategies have been incorporated into this 
protocol.
It was recognized that history of venous thromboembolism (VTE) is an important potential 
risk. Participants with a history or family history of VTE are excluded from this study.
Overall, there is a favorable benefit-risk profile to support the continued development in 
Phase 3 of abrocitinib in the treatment of adult participants with AD for both the 100 mg and 
200 mg doses.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of abrocitinib may be found in the IB19, which is the single 
reference safety document (SRSD) for this study. The SRSD for the comparator agent, 
dupilumab, is the United States Package Insert (USPI)20.
3. OBJECTIVES, ESTIMANDS AND ENDPOINTS
Objectives
Endpoints
Primary

To compare the efficacy of 
abrocitinib 200 mg once daily 
(QD) versus dupilumab (as per 
label guidelines) in adult 
participants on background topical 
therapy with moderate to severe 
atopic dermatitis (AD).

Response based on achieving at least a 
4-point improvement in the severity of 
Peak Pruritus Numerical Rating Scale 
(PP-NRS4) from baseline at Week 2.

Response based on achieving the 
Eczema Area and Severity Index 


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Objectives
Endpoints
(EASI)-90 (≥90% improvement from 
baseline) at Week 4.
Key Secondary

To compare the efficacy of 
abrocitinib 200 mg once daily 
versus dupilumab on additional 
efficacy endpoints in adult 
participants on background topical 
therapy with moderate to severe 
atopic dermatitis (AD).

Response based on achieving the 
Eczema Area and Severity Index 
(EASI)-90 (≥90% improvement from 
baseline) at Week 16.
Secondary

To compare the efficacy of 
abrocitinib 200 mg once daily 
versus dupilumab on additional 
efficacy endpoints in adult 
participants on background topical 
therapy with moderate to severe 
atopic dermatitis (AD).

Response based on achieving a ≥90% 
improvement in the EASI total score 
(EASI-90) at all other scheduled time 
points up to Week 26;

Response based on achieving a 75% 
improvement in the EASI total score 
(EASI-75) at all scheduled time points 
up to Week 26;

Response based on 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 up to Week 26;

Response based on achieving at least a 
4-point improvement in the severity of 
PP-NRS4 from baseline at all 
scheduled time points except Week 2;

Time from baseline to achieve at least 
a 4-point improvement in the severity 
of PP-NRS4 scale;

Percent Change from Baseline in the 
% Body Surface Area (BSA) affected 
at all scheduled time points;

Percent Change from Baseline in the 
SCORing Atopic Dermatitis 


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Objectives
Endpoints
(SCORAD) at all scheduled 
timepoints;

Change from baseline in the Hospital 
Anxiety and Depression Scale 
(HADS) at all scheduled timepoints;

Change from baseline in Dermatology 
Life Quality Index (DLQI) at all 
scheduled time points;

Change from baseline in EuroQol 
Quality of Life 5-Dimension 5-Level 
Scale (EQ-5D-5L) at all scheduled 
time points;

Change from baseline in 
Patient-Oriented Eczema Measure 
(POEM) at all scheduled time points;

Change from baseline in Medical 
Outcomes Study – Sleep Scale (MOS-
Sleep Scale) at all scheduled time 
points;

Change from baseline in Skin Pain 
NRS at all scheduled time points;

Medicated topical background 
therapy-free days.
Safety

To compare the safety and 
tolerability of abrocitinib 200 mg 
QD versus dupilumab in adult 
participants on background topical 
therapy with moderate to severe 
AD.

Incidence of treatment-emergent 
adverse event (AE)s;

Incidence of serious adverse event 
(SAE)s and AEs leading to 
discontinuation;

Incidence of clinical abnormalities and 
change from baseline in clinical 
laboratory values, electrocardiogram 
(ECG) measurements, and vital signs.


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Objectives
Endpoints
Tertiary/Exploratory

To compare the efficacy of 
abrocitinib 200 mg QD versus 
dupilumab on Healthcare Resource 
Utilization (HCRU) in adult 
participants on background topical 
therapy with moderate to severe 
AD.

Change from baseline in the HCRU 
questionnaire at all scheduled time 
points.

To compare the effect of 
abrocitinib 200 mg QD versus 
dupilumab on the frequency and 
duration of scratching during the 
night and sleep quantity in adult 
participants on background topical 
therapy with moderate to severe 
AD using wearable accelerometry 
devices.

Number of scratching episodes during 
the evening sleep period that occur 
pre-treatment versus on-treatment, as 
derived from data analyses using 
wearable accelerometry monitors at 
scheduled time points;

Duration of scratching episodes during 
the evening sleep period that occur 
pre-treatment versus on-treatment, as 
derived from data analyses using 
wearable accelerometry monitors at 
scheduled time points;

Quantity of total sleep opportunity, 
total sleep time, percent time asleep, 
WASO, sleep onset latency, and 
number of wake bouts that occur 
pre-treatment versus on-treatment, as 
derived from data analyses using 
wearable accelerometry monitors at 
scheduled time points.

To evaluate the efficacy of 
abrocitinib 200 mg QD in adult 
participants on background topical 
therapy with hand eczema.

Response based on 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.
3.1. Estimands
The objective of the study is to demonstrate superiority of abrocitinib 200 mg once daily 
(QD) to dupilumab as measured by Peak Pruritus Numerical Rating Scale (PP-NRS4) 
response at Week 2 and EASI-90 response at Week 4. Additionally, this study is intended to 


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demonstrate that abrocitinib 200 mg QD is non-inferior to dupilumab and if non-inferior, to 
demonstrate the superiority to dupilumab as measured by EASI-90 response at Week 16.
There are two estimands for the study.
Estimand 1, composite estimand:

Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population; 

Variable: response based on achieving at least a 4-point improvement in the severity 
of PP-NRS4 from baseline at Week 2; for participants who drop out for any reason or 
use rescue therapy (Section 6.5.2) at any time during the treatment period, the 
response will be defined as “non-responsive” after that point;

Interventional effect: Effect of randomized treatment accounting for treatment 
adherence, rescue therapy, and response; the intercurrent event (drop-out or use of 
rescue therapy) is captured through the variable definition;

Population-level summary: differences in proportions of responders between
abrocitinib and dupilumab.
Estimand 1 composite estimand is the primary estimand for the primary and key secondary 
endpoints: PP-NRS4 response at Week 2, EASI-90 at Week 4, and EASI-90 at Week 16. 
Other binary outcome measures such as response based on PP-NRS4 and EASI-90 at all 
other scheduled timepoints, EASI-75, and IGA will follow the same structure.
Estimand 2, hypothetical estimand:  

Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population;  

Variable: Percent change from baseline in SCORAD at all scheduled timepoints;

Interventional effect: Effect of randomized treatment as if all participants maintain 
their randomized treatment; drop-out for any reason and use of rescue therapy are the 
intercurrent events; data after dropout or use of rescue therapy at any time during the 
treatment period will be censored;

Population-level summary: Difference in least-square means between abrocitinib and 
dupilumab.
Percent change from baseline or change from baseline to each specific post baseline 
scheduled time points in a continuous outcome measure such as HADS, POEM, DLQI, and 
EQ-5D-5L will follow the same structure as defined for SCORAD.


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3.2. Adjudication Committee
This protocol will use an independent adjudication committee to determine whether certain 
investigator-reported adverse events meet the definition of disease-related safety endpoints, 
using predefined endpoint criteria.
To help assess the specific, complex safety events related to malignancies, cardiovascular 
events, hepatic and opportunistic infections (including 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.
4. STUDY DESIGN
     
4.1. Overall Design
This is a randomized, double-blind, double-dummy, active-controlled, multi-center study to 
assess the efficacy and safety of abrocitinib 200 mg (2 x 100 mg tablets) administered 
orally QD compared with dupilumab 300 mg administered by subcutaneous injection every 
other week (as per label guidelines) in adult participants on background topical therapy, with 
moderate to severe AD.  The treatment duration is 26 weeks.  A total of approximately 
600 participants will be enrolled from approximately 220 sites globally.  Approximately 600 
participants will be randomly assigned to study intervention. There are primary efficacy 
assessments at Week 2 and Week 4, and a key secondary efficacy assessment at Week 16.  
Efficacy and safety endpoints will be assessed throughout the entire study. Exploratory 
endpoints related to hand eczema efficacy will be assessed throughout the study.
After providing informed consent, participants will be assessed for study eligibility at the 
screening visit.  Participants will undergo screening within 28 days prior to randomization. 
Use of screening procedures exceeding 28 days prior to randomization should be discussed 
with the Pfizer medical monitor.   
During the screening period, systemic treatments for AD will be washed out, as applicable, 
according to eligibility requirements (refer to Inclusion and Exclusion Criteria in Section 5.1
and Section 5.2, respectively).  Eligible participants must have a documented history, within 
6 months of the screening visit, of inadequate response to treatment with medicated topical 
therapy for at least 4 weeks or must have required systemic therapies for control of their 
disease within the previous year.  


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Eligible participants must meet the eligibility criteria at baseline.  In addition, participants 
must be willing and able to use standardized background topical therapy, as per protocol 
guidelines, throughout the duration of the study. 
Participants may be re-screened once if they fail the screening evaluation for reasons related 
to incidental transitory conditions.  Participants 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.
Participants who continue to meet eligibility criteria at baseline will undergo Day 1 
assessments and be randomized in a 1:1 ratio to receive abrocitinib 200 mg QD with 
dupilumab-matching placebo administered every other week or dupilumab 300 mg 
administered every other week (with a loading dose of 600 mg at baseline) with 
abrocitinib -matching placebo administered QD.  Investigators, participants, and the sponsor 
study team will be blinded as to treatment group.  
After Week 4, if medically necessary, participants with intolerable AD symptoms may 
receive locally-approved rescue therapy, at the investigator’s discretion, pursuant to the 
following guidelines (refer to Section 6.5.2).
The total treatment period is 26 weeks.  Participants discontinuing early from treatment, or 
who are otherwise ineligible for the B7451015 LTE study, will undergo a 4-week follow-up 
period.  At Week 24 in the treatment period, all participants will cease injectable dupilumab 
or its matching placebo.  Administration of abrocitinib 200 mg QD or its matching placebo 
will continue until Week 26. Efficacy and safety endpoints will be assessed throughout the
entire study.  Participants who complete the study through the Week 26 visit and are deemed 
eligible may enter the LTE Study B7451015.
See Section 10.12.3 for United Kingdom (UK) country-specific requirements.
For study estimands, refer to Section 3.1.
4.2. Scientific Rationale for Study Design
This study is part of the global Phase 3 clinical development program investigating the safety
and efficacy of abrocitinib in participants with moderate to severe AD.  Dupilumab is the 
most recent treatment available for the disease area and is expected to be a future standard of 
care.  The comparison of dupilumab 300 mg to abrocitinib 200 mg in this study will provide 
efficacy and safety data for use in treating participants.  In addition, medicated topical 
therapy is commonly used to treat moderate to severe AD.  For this reason, including 
background medicated topicals will mimic real world medical practice.  Due to the chronic 
nature of AD, the study will allow assessment of any difference in efficacy that may persist 
at month 6 of treatment.  This study is designed to specifically evaluate abrocitinib and 
dupilumab when co-administered with background medicated topical therapy in adults with 
moderate to severe AD.


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Participants with moderate to severe AD who also have hand eczema will undergo additional 
hand eczema assessments. The pathophysiology of atopic and non-atopic forms of hand 
eczema involve cytokines that can be affected through JAK1 inhibition, including ILγ, IL4, 
and IL13.45 Therefore, this study includes exploratory endpoints related to hand eczema 
efficacy.
Quantitatively evaluating nighttime scratch and sleep via accelerometry using digital 
wearables and associated algorithms, to passively and continuously monitor participants in 
their “home environment,” provides an opportunity to examine new and distinct endpoints. 
Moreover, this evaluation contributes to the understanding how scratch and sleep endpoints 
correlate to currently used measures of AD severity. The amount and duration of nighttime 
scratching and the duration and arousals from the total sleep opportunity (nighttime sleep) 
will be assessed using accelerometry, in selected countries. 
Banked Biospecimens will be collected for pharmacogenomic/genomic/biomarker analyses 
and retained in the Biospecimen Banking System (BBS), which makes it possible to better 
understand the study intervention’s mechanism of action and to seek explanations for 
differences in, for example, exposure, tolerability, safety, and/or efficacy not anticipated 
prior to the beginning of the study. 
4.3. Justification for Dose
The original 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 AD.  The 200 mg QD dose as a monotherapy is expected to 
provide efficacy similar to that of currently approved systemic treatments (eg cyclosporine, 
systemic corticosteroids and dupilumab) in moderate to severe AD, based on dose-response 
modeling of IGA response in the Phase 2 study, and was therefore selected as the high dose 
for evaluation in Phase 3 studies.  
The 200 mg dose demonstrated acceptable safety and tolerability in the Phase 2 study and in 
the completed Phase 3 studies (B7451012 and B7451013).  Further details are available in 
the IB.  The dosing regimen of dupilumab used in the study will be based on the approved 
USPI.20
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 the last visit or the last scheduled procedure shown in the Schedule of 
Activities.
The end of the study is defined as the date of the last visit of the last participant in the study 
or last scheduled procedure shown in the Schedule of Activities for the last participant in the 
trial globally.


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5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
Participant eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before participants are included in the study.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participants must be 18 years of age or older inclusive, at the time of signing the 
informed consent. 
Type of Participant and Disease Characteristics
2. Participants who meet all of the following atopic dermatitis criteria:

Clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for 
at least 6 months prior to Day 1 and has confirmed atopic dermatitis at the 
screening and baseline visits according to Hanifin and Rajka criteria for AD.21
Refer to Appendix 9.

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 within the past year. 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 (BSA 10%, IGA 3, EASI 16, and PP-NRS severity 
score 4 on the day of the baseline visit).     


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Sex
3. Male or Female
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.
     
a.
Male participants:
     No contraceptive measures are 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 definitions below in 
Section 10.4.3)
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), as described below, during the intervention period 
and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s).  If a highly effective method that is user dependent is 
chosen, a second effective method of contraception, as described below, must also 
be used. The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
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
4. Capable of giving signed informed consent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
5. For the treatment of AD, the participant may use low- or medium-potency medicated 
and non-medicated topical therapy, with response to treatment remaining inadequate 
at baseline.  The participant must also be willing and able to comply with 
standardized background topical therapy, as per protocol guidelines Section 6.5.1, 
throughout the remainder of the study.
6. Participants willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, lifestyle considerations, and other study procedures.


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7. Participants must agree to avoid prolonged exposure to the sun and to refrain from the 
use of tanning booths, sun lamps, and other sources of ultraviolet light during the 
study.
8. If participants are receiving concomitant medications for any reason other than AD, 
these participants 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.  Administration of these stable regimen concomitant medications will be 
allowed to continue throughout the study.
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 including 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 
judgement 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).

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: Patient Health Questionnaire 8 items (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.


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3. Have increased risk of developing venous thromboembolism, e.g. deep vein 
thrombosis or pulmonary embolism:

History of venous thromboembolism, or 

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 coagulation disorder (e.g. Factor V Leiden).
4. A current or past medical history of conditions associated with thrombocytopenia, 
coagulopathy, or platelet dysfunction.
5. Receiving anti-coagulants or medications known to cause thrombocytopenia (unless 
considered safe to stop and washout for the duration of the study).
6. 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.
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 a known helminth infection;

Have active chronic or acute skin infection requiring treatment with systemic 
antimicrobials 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. 

Participants who are hepatitis B surface antigen (HBsAg) negative, hepatitis B
core antibody (HBcAb) positive, and hepatitis B surface antibody (HBsAb) 
positive at Screening will have reflex testing for hepatitis B Virus (HBV) 
deoxyribose nucleic acid (DNA). Participants who have HBV DNA above the 
lower limit of quantification (LLQ) are excluded. Participants who have HBV 


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DNA negative or below LLQ may be randomized but will have HBV DNA 
testing repeated at Week 16 and Week 26 End of Treatment (EOT) visit, or 
Early Discontinuation (ED) visit, whichever is sooner.

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 known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
10. 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.
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. Require treatment with prohibited concomitant medications (refer to Section 6.5) or 
have received a prohibited concomitant medication within the specified timeframe 
prior to the first dose of study intervention(s).
13. Have evidence of active, 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 performed at or 
within the 12 weeks prior to Day 1.  NOTE: The QFT-G may be repeated once if 
the investigator deems this to be necessary. If approved by the Pfizer clinician, 
other TB testing may be performed by a local lab.  A negative QFT-G, 
Mantoux/PPD tuberculin skin test or other local lab TB test is required unless the 
participant has previously received a documented adequate course of therapy for 
latent (9 months of isoniazid in a locale where rates of primary multi-drug TB 
resistance are <5% or an acceptable alternative regimen per local standards of 
care) 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.

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.  Refer to Section 8.2.5.2
for requirements for Mantoux/PPD tuberculin skin testing. 


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
Chest radiograph (or chest computed tomography scan, or magnetic resonance 
imaging [MRI] if available) taken at screening with changes suggestive of active 
TB infection as determined by a qualified radiologist.  A chest X-ray or other 
appropriate imaging is required, unless previously performed and documented 
within 12 weeks prior to Study Day 1.

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
14. Participants who are vaccinated or exposed to a live or attenuated vaccine within the 
6 weeks prior to the first dose of study intervention(s), or who are expected to be 
vaccinated or to have household exposure to these vaccines during treatment or 
during the 6 weeks following discontinuation of study intervention(s).
15. Participants who have received prior treatment with any systemic JAK inhibitors.  
Prior treatment with topical JAK inhibitors is not exclusionary.
16. Previous treatment with IL-4 or IL-13 antagonists, including dupilumab, 
lebrikizumab, or tralokinumab, or a history of hypersensitivity, intolerance, adverse 
event, or allergic reaction associated with prior exposure to excipients in these 
products.
17. Have received any of the following treatment regimens specified in the timeframes 
outlined below:
Within 1 year of first dose of study intervention(s):

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(s):

Other biologics: within 12 weeks of first dose of study intervention(s) or 
5 half-lives (if known), whichever is longer.


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Within 4 weeks of first dose of study intervention(s):

Use of oral immunosuppressive drugs (eg, CsA, azathioprine, methotrexate, 
systemic corticosteroids, mycophenolate-mofetil, IFN-) within 4 weeks of first 
dose of study intervention(s) 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 (refer to Appendix 10) within 
5 half-lives of the inducer plus 14 days of first dose of study intervention(s).  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(s).  

Phototherapy narrowband UVB (NB-UVB) or broadband 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 interventions:

Use of CYP2C9 and CYP2C19 inhibitors within 1 week of first dose of study 
intervention(s) or within 5 half-lives (if known) of the inhibitor, whichever is 
longer.  NOTE: Half-life refers to the half-life of the parent drug and its 
metabolites, which are inhibitors, as detailed in Appendix 10.

Anti-platelet drugs.  NOTE: low dose acetyl salicylic acid (100 mg QD) is 
permitted, for the purpose of cardiovascular prophylaxis, at the discretion of the 
investigator.
Prior/Concurrent Clinical Study Experience
18. Participation in other studies involving study intervention(s) within 8 weeks or within 
5 half-lives (if known), whichever is longer, prior to study entry and/or during study 
participation.  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 Medical Monitor (or designee).  
Participants cannot participate in studies of other investigational or experimental 
therapies or procedures at any time during their participation in this study.


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Diagnostic assessments
19. 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.
20. ANY of the following abnormalities in clinical laboratory tests at screening, as 
assessed by the study-specific laboratory and confirmed by a single repeat, if deemed 
necessary:

Absolute neutrophil count of <1.2 x 109/L (<1200/mm3);

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.
21. 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 enrollment in the study.
Other Exclusions
22. Have undergone significant trauma or major surgery within 1 month of the first dose 
of study interventions.
23. 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 


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Pfizer employees, including their family members, directly involved in the conduct of 
the study.
5.3. Lifestyle Considerations
1. On study visit days, participants must not administer study intervention until 
instructed to do so by the investigator or designated study site staff.  The study sites 
need to ensure PROs are completed and clinical assessments performed before dose is 
administered.
2. On study visit days, showering or bathing is permitted prior to attending the study 
visit.
3. On study visit days, topical therapies (ie, non-medicated topical therapy and 
medicated topical therapy, per protocol guidelines as described in Section 6.5) 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).
4. 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 from the permitted list of contraception methods (see 
Appendix 4 Section 10.4) and will confirm that the participant has been instructed in 
its consistent and correct use.  At time points indicated in the SoA, 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 or partner.
5. Male participants are not required to use contraception.
5.3.1. Meals and Dietary Restrictions
On study visit days as per the Schedule of Activities, participants must comply with fasting 
requirements for at least 8 hours prior to the visit. Water and permitted non-study 
medications are allowed (Section 6.5.1).
If the participant experiences nausea, consideration should be given to administering the oral 
study intervention with food.


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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. Vaccine and Exposure to Infections Guidelines
5.3.3.1. Participant Specific Recommendations
It is recommended that all participants should be up-to-date with respect to standard-of-care 
vaccinations (as defined by their country health ministry or AD guidelines). Vaccination of 
participants with live components is prohibited within the 6 weeks prior to first dose of study 
intervention. 
5.3.3.2. Guidance Regarding Household Contact Vaccine-Related Exposure
Current routine household contact with children and others who have been vaccinated with 
live vaccine components may pose a risk during treatment and for 6 weeks following 
completion of the study. Some of these vaccines include varicella (“chickenpox”) vaccine, 
oral polio vaccine, and the inhaled flu vaccine. Following vaccination with live component 
vaccines, the virus may be shed in bodily fluids, including stool, and there is a potential risk 
that the virus may be transmitted. General guidelines for immunosuppressed participants 
suggest that exposure (through routine contact) should be avoided following vaccination (of 
others) with these vaccines for the stated time period:
a. Varicella or attenuated typhoid fever vaccination for 4 weeks following 
vaccination.
b. Oral polio vaccination for 6 weeks following vaccination.
c. Attenuated rotavirus vaccine for 10 days following vaccination.
d. FluMist® (inhaled flu vaccine) for 1 week following vaccination.
e. Measles, Mumps and Rubella vaccine for 4 weeks following vaccination.
f. Yellow fever vaccine for 4 weeks following vaccination.
Participants should avoid exposure to vaccinated or infected persons and contact the 
investigator promptly should they develop signs or symptoms of infections.
5.3.4. Surgery
During the study, no elective surgery should occur without first consulting with the Pfizer 
clinician or designee. 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 


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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.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/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 criterion for participation in this study (screen failure) may 
be rescreened once 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 criteria 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.


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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.
6.1. Study Intervention(s) Administered
NOTE:  Abrocitinib may be referred to as PF-04965842. 
ARM Name
Abrocitinib 
Dupilumab
Abrocitinib 
Matching Placebo
Dupilumab 
Matching Placebo
Intervention 
Name
Abrocitinib   
Dupilumab
Placebo
Placebo
Type 
Small 
molecule
Biological product
Other
Other
Dosage Form
Tablet
Injectable
Tablet
Injectable
Dose Strength
200 mg
300 mg
0 mg
0 mg
Dosage
100 mg x 2 
tablets
300 mg x 1 
injection (2 
baseline injections)
0 mg x 2 tablets
0 mg x 1 injection (2 
baseline injections)
Route of 
Administration
Oral
Subcutaneous
Oral
Subcutaneous
Sourcing
Provided 
centrally by 
the Sponsor.
Provided centrally 
by the Sponsor.
Provided centrally by 
the Sponsor.
Provided centrally by the 
Sponsor.
Packaging and 
Labeling
Study 
Intervention 
will be 
provided in 
bottles. Each 
bottle will be 
labeled as 
required per 
country 
requirement.
Study Intervention 
will be provided in 
prefilled syringes. 
Each prefilled 
syringe 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 prefilled 
syringes. Each prefilled 
syringe will be labeled as 
required per country 
requirement.
6.1.1. Administration of Study Interventions

Treatment duration is 26 weeks (with the blind maintained throughout).

A guidance document with detailed dosing instructions will be provided to the 
participant to support at-home dosing.

Participants who do not enroll into the long-term extension study, B7451015, will 
enter a 4-week follow-up post-treatment period. (See Section 10.12.3 for UK country-
specific requirements).


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6.1.1.1. Administration of Abrocitinib/Matching Placebo

Orally administered study intervention, abrocitinib 200 mg, or its matching placebo, 
will be administered QD from Day 1 to Week 26.  Participants will be dispensed 2 
bottles of oral study intervention at the Day 1, Week 4, Week 8, Week 12, Week 16 
visits, and 3 bottles of study intervention at the Week 20 visit. 

Participants will be given clear dosing instructions to take two tablets of study 
intervention once daily by mouth, preferably in the morning whenever possible, at 
approximately the same time of day.  On study visit days, participants (and 
caregivers, if applicable) are to be instructed to refrain from dosing at home and are to 
administer study intervention in the clinic under observation, at the end of the study 
visit.

Participants will swallow the oral study intervention whole and will not manipulate or 
chew the medication prior to swallowing.  Oral study intervention may be taken with 
or without food, other than on study visit days where fasting is required.  If the 
participant experiences nausea, consideration should be given to administering the 
oral study intervention with food.
6.1.1.2. Administration of Dupilumab/Matching Placebo

Injectable study intervention, dupilumab 300 mg (with a loading dose of 600 mg at 
baseline) or its matching placebo (two injections at baseline; to dummy the loading 
dose), will be administered at the site on Day 1, Week 2, Week 4, Week 8, Week 12, 
Week 16, and Week 20 under the observation of the injection administrator/trainer at 
the end of the study visit, and at home by the participant (or caregiver, if applicable) 
at Week 6, Week 10, Week 14, Week 18, Week 22, and Week 24.  

Participants will be dispensed prefilled syringes containing injectable study 
intervention at the Day 1 (2 syringes dispensed and administered), Week 2 (1 syringe
dispensed and administered), Week 4, Week 8, Week 12, and Week 16 visits (2 
syringes dispensed per visit; 1 syringe administered every 2 weeks).  Participants will 
be dispensed 3 prefilled syringes at the Week 20 visit (1 syringe administered every 2 
weeks). 

The injection administrator/trainer will instruct the participant (or caregiver, if 
applicable) on the proper aseptic technique to administer a subcutaneous injection 
when using the prefilled syringes.  

The first injection at the Day 1 visit will be administered by the injection 
administrator/trainer and used to train the participant (or caregiver, if applicable) 
on correct injection technique.  

The second injection will be administered by the participant (or caregiver, if 
applicable) immediately following the first injection, under the observation of the 
injection administrator/trainer.  


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
If any issues with technique are observed, the injection administrator/trainer must 
retrain the participant appropriately.  

All injections should be administered in accordance with the dupilumab drug 
label.

The investigator should assign the responsibility of the injection 
administrator/trainer to a member of the study site staff who will not participate in 
any other study-related activities, ensuring that all other site staff do not risk 
becoming accidentally unblinded.  Contact between the injection 
administrator/trainer and study participants should be kept to a minimum.  The 
injection administrator/trainer must not take any action that may potentially reveal 
treatment assignment to the participant or site staff.  The investigator, site staff, 
and any study participants other than the injection administrator/trainer must not 
be allowed to know the study intervention assigned to any study participant and 
must not be allowed to see the treatment records.
6.1.2. Medical Devices
The medical devices (or devices manufactured by and/or for Pfizer by a third party) provided 
for use in this study are:

pre-filled syringes for subcutaneous injection of dupilumab and matching placebo. 
Instructions for medical device use are provided in the Investigational Product Manual (IP 
Manual).
Pre-filled medical device incidents, including those resulting from malfunctions of the 
device, must be detected, documented, and reported by the investigator throughout the study 
(refer to Section 8.3.6 and Appendix 7).
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).


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4. Further guidance and information for the final disposition of unused study 
interventions are provided in the Investigational Product Manual (IP Manual).
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label.
6. Study interventions should be stored in their original containers and in accordance 
with the labels.
7. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention.
8. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  It will not be considered a protocol deviation if Pfizer 
approves the use of study intervention after the temperature excursion.  Use of the 
study intervention prior to Pfizer approval will be considered a protocol deviation.  
Specific details regarding the definition of an excursion and information the site 
should report for each excursion will be provided to the site in the IP Manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP Manual.
6.2.1. Preparation and Dispensing
The oral study intervention will be dispensed using an interactive response technology (IRT) 
drug management system at the Day 1, Week 4, Week 8, Week 12, and Week 16 visits (two 
bottles dispensed each visit), and the Week 20 visit (three bottles dispensed this visit).  A 
qualified staff member will dispense the study interventions via unique container numbers on 
the bottles provided, in quantities appropriate for the study visit schedule.  The 
participant/caregiver should be instructed to maintain the product in the bottle provided 
throughout the course of dosing and return the bottle to the site at the next study visit.


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The injectable study intervention will be provided as prefilled syringes (PFSs) packaged and 
dispensed in cartons with tamper-evident seals.  The study interventions will be dispensed 
using an IRT drug management system at the Day 1 (2 syringes dispensed and administered), 
Week 2 (1 syringe dispensed and administered), Week 4, Week 8, Week 12, and Week 16 
visits (2 syringes dispensed per visit; 1 syringe administered every 2 weeks).  Participants 
will be dispensed 3 prefilled syringes at the Week 20 visit (1 syringe administered every 2 
weeks). A qualified staff member will dispense the study interventions via unique container 
numbers in the cartons provided, and in quantities appropriate so that participants will 
receive enough PFSs to cover the number of doses until the next scheduled clinic visit.  The 
participant/caregiver should be instructed to maintain the product in the cartons provided, 
and the cartons should not be opened until the study intervention is to be administered.
Refer to the IP manual for instructions on how to prepare the study interventions for 
administration.  Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance.
The dupilumab and matching placebo will be administered by qualified site personnel or by 
the participant/caregiver according to the IP manual.  The study interventions will be 
administered to blinded participants.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation of participants to treatment groups will proceed through the use of an IRT system 
(interactive Web-based response [IWR]).  The block randomization method will be used, and 
participants will be stratified by baseline disease severity (IGA = 3 vs. IGA = 4).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when study intervention is being supplied via the IRT system.  The IRT system will provide 
a confirmation report containing the participant number, randomization number, and DU or 
container number assigned.  The confirmation report must be stored in the site’s files. 
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be re-dispensed to the participants.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Breaking the Blind
Investigators, participants and the sponsor study team will be blinded as to treatment group.  
At each site, an injection administrator/trainer will administer the first dose of dupilumab or 


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its matching placebo to train the participant (or caregiver, if applicable) in proper injection 
technique.  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 investigator is responsible for, and may break the blind for safety 
reasons, where the knowledge of actual treatment is essential for the further management of 
the participant.  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 or 
Medical Monitor.  The participant for whom the blind has been broken will be discontinued 
from the study and undergo the early discontinuation (ED) procedures.
6.4. Study Intervention Compliance
Participant compliance with study intervention will be assessed at each visit. Compliance 
will be assessed by direct questioning and counting of syringes/tablets as applicable.
Deviation(s) from the prescribed dosage regimen should be recorded in the electronic case 
report form (eCRF).
Participants will be issued an electronic dosing diary (eDiary) and will be educated to record 
the date and time of their dosing and date and time of their last meal before taking the study 
intervention.  Participants will also use the eDiary to record their daily use of standardized 
background topical therapy for the treatment of AD, as required and as per protocol 
guidelines in Section 6.5.1, beginning at Day 1 visit through the EOT visit.
Compliance with the dosing of study intervention will be monitored and verified by 
delegated site personnel through a combination of observed study intervention administration 
at study visits, 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 may be temporarily withheld for a maximum of 28 days at investigator's 
discretion due to abnormal laboratory tests or adverse event.  Refer to Section 7.1.1 for 
further guidance on temporary withholding of study intervention.  Doses not taken for the 
reasons mentioned above do not constitute protocol deviations or medication errors and 
should not be considered dosing errors but should be noted in the dosing log with the reason 
for reduced drug consumption.
Compliance with background topical therapy guidelines in Section 6.5.1 will be monitored 
and verified by delegated site personnel through a combination of review of the electronic 
diary, and discussion with the participant, which will be documented in the source 
documents.


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Other than for the above reasons, the following compliance cases will be considered 
medication errors and will be discussed with the sponsor for possible withdrawal from the 
study:

Participants interrupting oral study intervention for more than 4 consecutive days or 
for a total of more than 7 days between visits;

Participants interrupting injectable study intervention for ≥ 2 doses between visits (≥ 
4 week visit intervals);

Participants administering >8 tablets in 1 day or administering 4 tablets/day for 
4 consecutive days;

Participants administering >1 prefilled syringe every 2 weeks, with the exception of 
the initial loading dose of 2 prefilled syringes on Day 1;

Participants who have an overall compliance of <80% or >120% between visits for 
oral study intervention; 
Non-compliance with background topical therapy will not be considered medication error.
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 also Section 8.3.10).
6.4.1. Abrocitinib Compliance
Study intervention should be administered in the morning.  Participants should be instructed 
that if an oral dose is inadvertently missed then it should be taken as soon as remembered, 
but not within 12 hours of the next scheduled dose.  
From the Day 1 visit onward, participants will be dispensed abrocitinib or 
abrocitinib-matching placebo to take home with them for self-administration on non-study 
visit days.
6.4.2. Dupilumab Compliance
There are viscosity differences between dupilumab and the matched placebo, and as such 
there is a potential for the administrator/trainer who may have previous experience 
administering dupilumab to notice this difference in viscosity.  Although no injection 
administrator/trainer will know the treatment allocation of participants, as a risk mitigation 
against accidental unblinding affecting study integrity this injection administrator/trainer will 
only administer injectable study intervention, or observe/train participants administering 
injectable study intervention, and will account/reconcile any unused syringes returned by 
participants, will be isolated from all other study activities, and will be treated as if unblind.  
Throughout the protocol, these individuals will be referred to as "injection 
administrator/trainer" in order to make this clear distinction from other site personnel.


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When injectable study intervention is administered at the research facility, it will be 
administered under the supervision of the injection administrator/trainer only. 
If the participant is unwilling/unable to self-administer the injectable study intervention or 
arrange for a caregiver to administer the injectable study intervention, then it is permissible 
for the site to arrange for the participant to return to the site for administration by the 
injection administrator/trainer.  
Participants will be directed to bring any used and unused syringe cartons to visits following 
administration at home.  Study sites will provide participants with a sharps container for 
disposal of used syringes.  Participants will return this sharps container to the study site at the 
final visit for disposal.
If an injectable dose is missed, participants (or caregivers, if applicable) should be instructed 
to administer the injection within 7 days from the missed dose and then resume the 
participant’s original schedule.  If the missed dose is not administered within 7 days, 
participants (or caregivers, if applicable) should be instructed to wait until the next dose on 
the original schedule.
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.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (refer to Appendix 4).
Participants must abstain from taking prescription or nonprescription drugs (including 
vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a 
potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study 
intervention until completion of the follow-up visit (refer to Appendix 10 for washout 
periods for CYP2C9 inhibitors and inducers), unless, in the opinion of the investigator and 
sponsor, the medication will not interfere with the study.
Participants will abstain from all prohibited concomitant medications as described in 
Section 6.5.3 and Appendix 10 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 


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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.
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. Following Day 1, the addition of concomitant medications or any change in the
dosage should be limited to those considered medically essential.
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.
The concomitant medication for any reason must be a locally-approved medication and dose. 
Participants are not allowed any other investigational drugs or treatments during the study.
Participants should report any changes to medications during the study to the investigator as 
soon as they occur. Medication changes must be documented in the participant’s record and 
eCRF.
6.5.1. Permitted Concomitant Treatments
Background Topical Therapy
Participants must comply with standardized background topical therapy guidance throughout 
the study. Medicated and non-medicated background topical therapy will not be provided 
directly by the sponsor. Standardized background topical therapy begins on Day 1 but topical 
therapies can be taken during the screening period since washout of topical therapies for AD 
is not required. Standardized background topical therapy refers to the guidance below, in 
accordance with the local standard of care and according to the Investigator’s usual practice:
Non-medicated Topical Therapy

Non-medicated topical emollient without other active ingredients indicated to treat 
AD, or other additives which could affect AD (eg, hyaluronic acid, urea, ceramide or 
filaggrin degradation products) must be applied at least twice daily to all body areas 
affected with AD starting on Day 1 and throughout the remainder of the study.
Medicated Topical Therapy

TCS must be applied once daily to areas with active lesions, starting on Day 1 
(Baseline) and throughout the study, according to the guidance below:

Medium potency TCS (eg, Triamcinolone acetonide 0.1% cream or fluocinolone 
acetonide 0.025% ointment) must be applied to body areas with active lesions that 


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are suitable for the use of medium potency TCS. Participants must be clinically 
monitored for toxicity to TCS and stepped down as needed.

After lesions are under control (clear or almost clear), treat once daily for a 
further 7 days, then stop;

If lesions return then resume treatment with medium potency TCS, but use the 
approach described above upon lesion resolution.

If the participant experiences toxicity attributable to the background TCS, the 
following step-down is allowed: 

Change from medium-potency TCS to low-potency TCS once daily (if the 
participant has been receiving medium-potency TCS); OR 

Change from a TCS to a topical calcineurin inhibitor or a 
phosphodiesterase type 4 inhibitor; OR 

Discontinue background medicated topical treatment, if there is 
documented evidence that the participant did not tolerate any of the 
background medicated topical treatments allowed in the protocol.

Low potency TCS (ie, hydrocortisone 1% cream) must be applied to body 
areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin 
atrophy, etc.) with active lesions instead of medium potency TCS or to body 
areas where continued treatment with medium potency TCS is considered 
unsafe. Participants must be clinically monitored for toxicity to TCS and 
stepped down as needed.

After lesions are under control (clear or almost clear), treat once daily for 
a further 7 days, then stop;

If lesions return then resume treatment with low potency TCS, but use the 
approach described above upon lesion resolution.
TCI (eg, tacrolimus, pimecrolimus) or a PDE4 inhibitor (eg, crisaborole) may be used instead 
of corticosteroids in body areas of thin skin (face, neck, intertriginous, and genital areas, 
areas of skin atrophy, etc.) with active lesions or if continued treatment with TCS of any 
potency is considered unsafe, and according to locally approved label at the investigator’s 
discretion and considering prior response or intolerance to these medications.  
NOTE: Background topical therapy must not be applied prior to attending a study visit, on 
the day of the study visit. Background topical therapy should instead be applied after the 
visit, on study visit days.


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Other Permitted Concomitant Treatments
The following other concomitant AD therapies are permitted during the study and will not be 
provided by the sponsor:

Oral antihistamines.
The following concomitant medications are permitted during the study:

Corticosteroid inhalers and intranasal sprays are permissible for participants receiving 
a stable dose;

Ophthalmic corticosteroids are permissible for participants receiving a stable dose;

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 gram per 
day;

Dietary supplements (defined as vitamins and minerals, and purified food substances) 
of standard potency are allowed in amounts not known to be associated with adverse 
effects (such as hyper-vitaminosis).
Locally approved treatments for AD other than what is outlined in this section, including 
topical or systemic medications, are considered rescue therapy.
Reference Appendix 10 for prohibited concomitant medications.
6.5.2. Rescue Therapy for Atopic Dermatitis
The study site will not supply rescue therapy for AD. This will be obtained locally.
After Week 4, if medically necessary, participants with intolerable AD symptoms may 
receive locally-approved rescue therapy, at the investigator’s discretion, pursuant to the 
following guidelines.

Rescue therapy may include high-potency TCS for up to 2 weeks at a time or 
systemic corticosteroids for up to 10 days at a time according to local product label,
or other systemic therapy according to local productlabel.8,52

Investigators should make every attempt to conduct efficacy and safety assessments 
(eg, disease severity scores, safety labs) immediately before administering rescue 
therapy. An unscheduled visit may be used for this purpose if necessary.


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
Participants receiving systemic rescue therapy must temporarily discontinue study 
intervention during the time they take the systemic rescue therapy. Participants 
receiving systemic rescue therapy should continue study visits and assessments.

Participants receiving topical rescue therapy may continue to receive study 
intervention concurrently. Participants receiving topical rescue therapy should 
continue study visits and assessments. 

Rescue therapy administration must be recorded.
See Section 10.12.2 for Czech-Republic country-specific requirements.
6.5.3. Prohibited Medications and Treatments
Participants are required to discontinue and avoid using certain medications and treatments 
(refer to Inclusion Criteria [Section 5.1], Exclusion Criteria [Section 5.2], and Appendix 10). 
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 and low- or medium-potency medicated topical therapy. Starting on Day 1, 
standardized background topical therapy will be used as per protocol guidance in 
Section 6.5.1. After Week 4, rescue therapy for AD with high-potency TCS or systemic 
corticosteroids may be used as per protocol guidance in Section 6.5.2.
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.  Prior treatment with topical JAK inhibitors is not exclusionary.
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. Restrictions on 
certain vaccinations are described in Section 5.3.3.
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 judgement on the 
ongoing eligibility of any participant with prohibited medication use during the study.
6.6. Dose Modification
No dose modifications of either study intervention are allowed.
6.7. Intervention after the End of the Study
No intervention will be provided to study participants at the end of the study.


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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. Per the study estimands, if study intervention is permanently discontinued, the 
participant will remain in the study to be evaluated for EOT assessments (as per the Schedule 
of Activities) (See Section 6.5.2). 
If a participant has a clinically significant, treatment-emergent, abnormality at the time of 
withdrawal from the study, the Pfizer Medical Monitor (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.  
Note that discontinuation of study treatment does not represent withdrawal from the study.  
Refer to Appendix 11 for discontinuation criteria.
Refer to 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.
Discontinuation of study intervention for abnormal liver function should be considered by the 
investigator when a participant meets one of the conditions outlined in Appendix 6 or if the 
investigator believes that it is in best interest of the participant.
     
If a clinically significant finding is identified (including, but not limited to changes from 
baseline in Fridericia-corrected Q wave interval [QTcF]) after enrollment, the investigator or 
qualified designee will determine if the participant can continue in the study and if any 
change in participant management is needed. This review of the ECG printed at the time of 
collection must be documented. Any new clinically relevant finding should be reported as an 
AE.  Refer to Appendix 8 for ECG values of potential clinical concern.
See the SoA 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
An investigator can temporarily interrupt oral study intervention for up to a maximum of 28 
consecutive days and up to 2 consecutive doses of injectable study intervention for a 
participant, for safety reasons or while monitoring abnormal laboratory tests if the 
investigator judges that this is necessary. In the case of study intervention(s) being withheld, 
all study intervention(s) that the participant is receiving should be withheld (ie, both oral and 
injected study intervention, as applicable). The investigator should use their judgement with 
regard to unscheduled visits/laboratory/clinical assessments required to monitor the 
participant during this timeframe. If within this timeframe the investigator judges that it is 


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safe to restart dosing, then the participant may restart the study intervention. If the 
investigator judges that it is not safe to restart dosing within this timeframe then the 
participant must be permanently discontinued from study intervention, have an End of 
Treatment visit, and enter the 4-week follow-up period (See Section 10.12.3 for UK country-
specific requirements). Doses not taken for the reasons mentioned above do not constitute 
protocol deviations or medication errors and should not be considered dosing errors but 
should be noted in the dosing log with the reason for reduced drug consumption clearly 
described.
7.2. Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. See also 
Section 10.11.

At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA. See the SoA for data to be collected at the 
time of study discontinuation and follow-up and for any further evaluations that need 
to be completed.  The participant will be permanently discontinued both from the 
study intervention and from the study at that time.

The early discontinuation visit applies only to participants who are randomized and 
then are prematurely withdrawn from the study.  Participants should be questioned 
regarding their reason for withdrawal.  The participant will be permanently 
discontinued both from the study intervention and from the study at that time.

If the participant withdraws consent (see below) 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 
a withdrawal of consent.

If a participant withdraws from the study, he/she may request destruction of any 
remaining samples but data already generated from the samples will continue to be 
available, and may be used to, to protect the integrity of existing analyses. The 
investigator must document any such requests in the site study records.

When a participant withdraws from the study because of an SAE, the SAE must be 
recorded on the CRF and reported on the clinical trial (CT) SAE Report.

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 interventions will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 


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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 Appendix 1.
All attempts should be documented in the participant’s medical records.  If it is determined 
that the participant has died, the site will use locally permissible methods to obtain the date 
and cause of death.  If the investigator’s use of a third-party representative to assist in the 
follow-up portion of the study has been included in the participant’s informed consent, then 
the investigator may use a sponsor-retained third-party representative to assist site staff with 
obtaining the participant’s contact information or other public vital status data necessary to 
complete the follow-up portion of the study.  The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information.  If, after all attempts, the participant remains lost to follow-up, 
then the last-known-alive date as determined by the investigator should be reported and 
documented in the participant’s medical records.
Participants may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 


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reasons, or the inability of the participant to comply with the protocol-required schedule of 
study visits or procedures at a given study site.  Participants that discontinue study 
intervention will remain in the study and must have their end of treatment visit within 1 week 
after their last dose and will then enter the 4-week follow-up period.  Refer to Appendix 11
for guidelines for monitoring and discontinuation. 
If the participant withdraws from the study, and also withdraws consent for disclosure of 
future information, no further evaluations should be performed, and no additional data should 
be collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
8. STUDY ASSESSMENTS AND PROCEDURES
Every effort should be made to ensure that protocol required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
wellbeing of the participant. Guidance on the conduct of study procedures in the context of 
COVID-19 or other virus/infection or public health related travel restrictions or emergency is 
described Appendix 10.13. When a protocol required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.

Study procedures and their timing are summarized in the SoA. 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 SoA, 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 approximately 28 days prior to administration of the study intervention to 
confirm that they meet the participant selection criteria for the study. Use of 
screening procedures exceeding 28 days prior to randomization should be discussed 
with the Pfizer medical monitor.  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 of Appendix 1.


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
If the Mantoux PPD tuberculin skin test is given, the participant must return between 
48-72 hours post-injection for induration evaluation.

Due to the 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. During the fasting period, participants should refrain from all 
food and liquids (water and permitted non-study medications are allowed).

ECGs will be interpreted by a central reader for all visits where it is performed.

Urine pregnancy test must be performed prior to dosing with the study intervention 
for WOCBP through the EOT visit.

Prior to attending a study visit, participants are allowed to shower and bathe but 
should not moisturize or apply emollient.

Participants will be instructed about the use of standardized background topical 
therapy (refer to Section 6.5.1).

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 SoA.
8.1. Efficacy Assessments
8.1.1. Rater Qualifications 
Clinical evaluations of AD and hand eczema 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 and 
hand eczema when designated by the primary site Investigator. The clinical 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.


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8.1.2. Eczema Area and Severity Index (EASI)
The EASI quantifies the severity of a participant’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 Table 1.
Table 1.
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


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Table 1.
Clinical Sign Severity Scoring Criteria for the Eczema Area and Severity 
Index (EASI)
Score
Description
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 
atopic dermatitis in a body region can be used to determine the extent (%) to which a body 
region is involved with atopic dermatitis (Table 2).  When measuring, the handprint unit 
refers to the size of each individual participant’s hand with fingers in a closed position.
Table 2.
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 extent (%) to which each of the four body regions is involved with atopic dermatitis is 
categorized to a numerical Area Score using a non-linear scaling method according to the 
following BSA scoring criteria (Table 3).
Note: The BSA for a subset of body regions (scalp, palms and soles of feet) assessed in 
Table 2 will be entered in the eCRF.
Table 3.
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


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Table 3.
Eczema Area and Severity Index (EASI) Area Score Criteria
Percent BSA with Atopic Dermatitis in a 
Body Region
Area Score
90 - 100%
6
Body Region Weighting: Each body region is weighted according to its approximate 
percentage of the whole body (Table 4).
Table 4.
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 
the Body Region Weighting to provide a body region value, which is then summed across all 
4 body regions resulting in an EASI score as described in Equation 3 on the following page.
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 atopic dermatitis.
8.1.2.1. 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 3).  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 atopic dermatitis.  
8.1.3. SCORing Atopic Dermatitis (SCORAD)
SCORAD is a validated scoring index for atopic dermatitis, which combines extent (0-100), 
severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored 
using a visual analog scale (0-10). 


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Extent (A, maximum score of 100%)
To determine extent of AD, rule of 9 is used to calculate body surface area affected by AD as 
a percentage of the whole-body surface area.  Body surface area as percentage of total body 
surface area for each body region is as follows:

Head and neck 9%; 

Upper limbs 9% each; 

Lower limbs 18% each; 

Anterior trunk 18%; 

Back 18%; 

1% for genitals. 
The score for each body region is added up to determine the BSA affected by AD (A), which 
has a possible maximum score of 100%. 
Severity (B, maximum score of 18)
A representative area of AD is selected.  In this area, the severity of each of the following 
signs is assessed as none (0), mild (1), moderate (2) or severe (3). 

Erythema (reddening);

Edema (swelling)/papulation;

Oozing/crusting; 

Excoriation (scratch marks);

Skin thickening (lichenification); 

Xerosis (dryness) (this is assessed in an area where there is no inflammation).
The severity scores are added together to give 'B' (maximum score of 18).
Subjective Symptoms (C, maximum score of 20)
Subjective symptoms, ie, itch and sleep loss, are each scored by the participant or caregiver 
using a visual analog scale (VAS) where “0” is no itch (or no sleep loss) and “10” is the 
worst imaginable itch (or sleep loss).  The value for each should reflect the average on a 10-
point scale for the last 3 days/nights.  These scores are added to give 'C' (maximum score 
of 20). 


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SCORAD Total Score
The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range 
from 0 to 103).
8.1.4. Investigator’s Global Assessment (IGA) of Atopic Dermatitis
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 Table 5. The assessment will 
be a static evaluation without regard to the score at a previous visit.
Table 5.
Investigator’s Global Assessment (IGA) of Atopic Dermatitis 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.
8.1.5. Standardized Background Topical Therapy
Participants will be instructed to keep a daily record of use of standardized background 
topical therapy. At each visit, the participant’s understanding of background topical therapy 
requirements (refer to Section 6.5.1) and adherence to the use of background topical therapy 
will be checked. Participants will be re-educated as required. Standardized background 


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topical therapy use and adherence with guidelines will be recorded daily in the participant 
eDiary during the treatment period, through the EOT visit:

Non-medicated topical therapy must be applied at least twice daily to all body areas 
affected with AD starting on Day 1, and continued through the EOT visit;

Refer to Section 6.5.1 for required background medicated topical therapy during 
treatment through the EOT visit.
8.1.6. 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 
handheld device to complete the PP-NRS 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 on the device. If a participant is unable to 
complete the PROs on the handheld device due to documented difficulty using the 
technological devices or other limitation, the participant will be permitted to enter or remain 
in the study (for example, if the participant doesn’t have internet access, he or she can 
complete the PROs offline and then they can upload the PROs to the internet when they 
return to the site and have internet access).  In the event of electronic malfunction, a 
replacement device will be shipped to the site.
In instances where an electronic device is used to collect the PRO data, the electronic version 
may differ slightly in format or wording compared with the paper version to facilitate 
electronic implementation.
All PROs should be completed as per the Schedule of Activities.
8.1.6.1. Peak Pruritus Numerical Rating Scale (PP-NRS)
The severity of itch (pruritus) due to AD will be assessed using the PP-NRS, a validated 
horizontal NRS.22,23 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 the PP-NRS 
assessment into an eDiary on a daily basis from the Screening visit through the Week 30 
visit.
8.1.6.2. Dermatology Life Quality Index (DLQI)
The DLQI is a validated general dermatology questionnaire that consists of 10 items to assess 
participant-reported health-related quality of life (daily activities, personal relationships, 
symptoms and feelings, leisure, work and school, and treatment).24 It has been extensively 
used in clinical trials for AD. The DLQI is a psychometrically valid and reliable instrument 
that has been translated into several languages, and the DLQI total scores have been shown to 


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be responsive to change. The minimally important difference for the DLQI has been 
estimated as a 3 to 5-point change from baseline.25
8.1.6.3. EuroQuol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)
The EQ-5D is a validated, standardized, generic instrument that is the most widely used 
preference-based health-related quality of life questionnaire in cost-effectiveness and health 
technologies assessment (HTA).26-29  Recently, a version was developed called EQ-5D-5L 
with 5 response levels on each dimension compared to the 3 response levels in the Euroquol 
Quality of Life 5-Dimension 3-Level Scale (EQ-5D-3L).26-32  
Measurement properties of the EQ-5D-5L demonstrated to be a valid version of the 3-level 
questionnaire that improved measurements by adding discriminatory power, reducing the 
ceiling, and establishing convergent and known-groups validity.26,28,30,31  Both the EuroQol 
EQ-5D-3L and EQ-5D-5L versions are well-established instruments used to measure health 
states and utilities in various diseases areas and assess mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression and health status using a VAS.29,33 The EQ-5D-3L was 
used previously in AD studies, including the dupilumab trials, to measure utilities.17,34-36
8.1.6.4. Healthcare Resource Utilization (HCRU) Questionnaire
The HCRU is a 14-item questionnaire.  This instrument is appropriate for use in participants 
aged 18 years and older.37
8.1.6.5. Patient-Oriented Eczema Measure (POEM)
The POEM is a validated 7-item PRO measure used to assess the impact of AD recalled over 
the past week.38-39
8.1.6.6. Hospital Anxiety and Depression Scale (HADS)
The HADS is a validated 14-item PRO measure used to assess states of anxiety and 
depression over the past week.40
8.1.6.7. Medical Outcomes Study (MOS) Sleep Scale
The Medical Outcomes Study Sleep Scale (MOS-Sleep) is a validated 12-item measure used 
to assess sleep quality in the pastweek. The instrument has been validated for use by 
participants 18 years and older.41
8.1.6.8. Skin Pain Numerical Rating Scale (SP-NRS)
The SP-NRS queries “worst skin pain” in the past 24 hours on an 11-point scale (0 [no skin 
pain] – 10 [worst skin pain imaginable]).42
8.1.6.9. Asthma Control Questionnaire (ACQ)
Asthma control for all participants with a history of asthma, regardless of whether they are 
receiving medication for their asthma, should be assessed at times specified in the Schedule 
of Activities (SoA) using the Asthma Control Questionnaire (ACQ). The ACQ measures the 
adequacy of asthma control and change in asthma control which occurs either spontaneously 


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or as a result of treatment. The ACQ has 6 questions and participants are asked to recall how 
their asthma has been during the previous week and to respond to the symptom questions on 
a 7-point scale (0 = no impairment, 6 = maximum impairment). The questions are equally 
weighted and the ACQ score is the mean of the 6 questions and, therefore, between 0 (totally 
controlled) and 6 (severely uncontrolled). 54, 55, 56
8.1.7. Exploratory Accelerometry
AD is often accompanied by nighttime pruritus as well as disrupted and reduced overall 
sleep. Pruritus can lead to scratching, which can result in a worsening of the lesions and a 
further perpetuation of the disease. All of these contribute to altered quality of life for the 
participant. Quantitatively evaluating nighttime scratch and sleep via accelerometry using 
digital wearables and associated algorithms, to passively and continuously monitor 
participants in their “home environment,” provides an opportunity to examine new and 
distinct endpoints. Moreover, this evaluation contributes to the understanding how scratch 
and sleep endpoints correlate to currently used measures of AD severity.
Academic collaborative studies have shown nighttime scratch (number of scratch events and 
scratch duration) in AD participants correlated to the Investigator’s Static Global 
Assessment. In addition, accelerometry data processed by Pfizer algorithms to measure 
nighttime scratch and sleep quantity were able to distinguish between scratch and non-scratch 
movements, validated by thermal videography/annotation, and were able to detect sleep 
quantity, correlated to polysomnography measures (Clinicaltrials.gov study 
NCT03490877).53 The amount and duration of nighttime scratching and the duration and 
arousals from the total sleep opportunity (nighttime sleep) will be assessed using 
accelerometry, in selected countries.  Participants will wear wrist-worn, watch-like, 
accelerometry devices to continuously monitor the frequency of day and night time 
scratching and sleep disturbance for 1 week prior to the Day 1 visit, for 2 weeks following 
the Day 1 visit, and for 1-week periods during the weeks after the Week 12, Week 16, Week 
20, and Week 26 visits.  
Participation in accelerometry assessments is voluntary.  Participants may refuse or remove 
the devices at any time, either entirely or for activities during which the devices are 
uncomfortable (ie, showering), without any impact on their study participation.  Participants 
may also wear the devices over sleeves for comfort.
The following will be measured by accelerometry and subsequent algorithm assessment:

Scratch (during the total sleep opportunity):

Number of scratching episodes;

Duration of scratching.

Sleep (during the evening/major rest period):

Duration of the total sleep opportunity; 


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
Total sleep time (total time and percent time asleep);

Sleep onset latency;

Number of wake bouts (total and per hour of sleep);

Wake after sleep onset (WASO);

Sleep efficiency.
Data will remain blinded during the accelerometry endpoint processing in order to reduce 
bias when analyzing accelerometry data.
8.1.8. Exploratory Assessments of Hand Eczema
8.1.8.1. History, Subtype, Clinical Signs, and Extent
Participants will undergo evaluation at the screening visit of the presence and chronicity of 
hand eczema.46 Not all participants are expected to have hand eczema. For participants with 
bilateral hand eczema, the Investigator will identify the worse hand, which will be the target 
hand for evaluation throughout the study. Participants with hand eczema will also undergo 
assessments of the subtype(s) (at sites that have capacity for this), clinical signs, and extent 
of hand eczema.46, 47, 48, 49, 50 They will also be examined to determine if they have eczema of 
the feet.47
8.1.8.2. Investigator’s Global Assessment (IGA) of Hand Eczema
The Investigator’s Global Assessment of hand eczema is scored on a 5-point scale (0-4), 
reflecting a global consideration of erythema, scaling, and fissuring/cracking of the target 
hand, selected at the screening visit.51 The clinical evaluator of hand eczema will perform an 
assessment of the overall severity of hand eczema of the target hand and assign an IGA score 
and category as described in Table 6. The assessment will be a static evaluation without 
regard to the score at a previous visit.
Table 6.
Investigator’s Global Assessment (IGA) of Hand Eczema Score
Score
Category
Descriptiona
0
Clear
No signs of hand eczema.
1
Almost Clear
Just perceptible scaling and/or erythema.
2
Mild
Mild scaling, and/or mild erythema and/or mild cracking.
3
Moderate
Moderate scaling, and/or moderate erythema and/or moderate 
cracking/ fissuring.
4
Severe
Severe scaling, and/or severe erythema and/or severe 
cracking/fissuring.
a. If the participant has bilateral hand eczema, the worse hand is assessed.


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8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
8.2.1. Medical History and Physical Examinations

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. Additionally, a record of prior vaccinations will be obtained to 
determine if the participant has received tetanus, diphtheria and/or pertussis vaccines 
within the past 5 years.

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.

Complete physical examinations must be performed by the investigator, 
sub-investigator or a qualified health professional per local guidelines.  Complete 
physical examinations consist of assessments of general appearance; skin; head, eyes, 
ears, nose and throat (HEENT); mouth; heart; lungs; breast (optional); abdomen; 
external genitalia (optional); extremities; neurologic function; and lymph nodes.  In 
addition, height (screening visit only) and weight (screening, Week 0, Week 12, and 
Week 20 visits) will also be recorded.

Targeted physical examinations must be performed by the investigator, 
sub-investigator or a qualified health professional per local guidelines and should 
include skin, heart, lungs, and abdomen and examination of body systems where there 
are symptom complaints by the participant.

Investigators should pay special attention to clinical signs related to previous serious 
illnesses.


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
All AEs regarding conjunctivitis should be referred for an ophthalmology exam.

All AEs regarding conjunctivitis, herpes zoster, and acne or folliculitis should have 
additional details collected.
8.2.2. Vital Signs

Temperature (oral or tympanic), pulse rate, respiratory rate, and blood pressure will 
be assessed (pre-dose, if applicable).

Blood pressure and pulse measurements will be assessed with the participant in a 
seated position, after at least 5 minutes of rest in a quiet setting without distractions, 
using a standard calibrated blood pressure measuring device.  A blood pressure 
device that uses multiple cuff sizes based on the arm circumference is the required 
type of device.  The appropriate cuff size for the participant must be used to ensure 
accurate measurement.  The arm circumference at the midpoint of the length of the 
upper arm should be measured to determine the appropriate cuff size in accordance 
with the specifications of the BP measuring device.  The same properly sized and 
calibrated blood pressure cuff will be used to measure blood pressure each time.  
Participants should be seated in a chair, back supported, and arms bared (free of 
restrictions such as rolled up sleeves, etc.) and supported at heart level.  
Measurements should be taken on the same arm at each visit (preferably non-
dominant).  Participants should refrain from smoking or ingesting caffeine during 
the 30 minutes preceding the measurements.

Vital signs will be measured in a seated position after 5 minutes rest and will 
include temperature, systolic and diastolic blood pressure, and pulse. Heart rate 
should be measured at approximately the same time as BP for a minimum of 30 
seconds.  When the timing of BP and pulse (heart) rate measurements coincides 
with a blood collection or other study procedure, BP and pulse (heart) rate should be 
obtained first.
8.2.3. Chest X-Ray
Chest X-ray or other appropriate diagnostic image (ie, computerized tomography or magnetic 
resonance imaging) to aid in TB status determination may be performed up to 12 weeks prior 
to Day 1.  Chest X-rays (posterior/anterior and lateral views) are required. Official reading 
must be located and available in the source documentation.
8.2.4. Electrocardiograms

A single 12-lead ECG will be performed at visits specified in the Schedule of 
Activities after the participant has rested for at least 10 minutes quietly in the supine 
position. ECG will be interpreted by a central reader.  Clinically significant or 
exclusionary ECG findings at the screening visit will result in screen failure.  


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
A participant’s screening ECG must not demonstrate clinically significant 
abnormalities prior to randomization.

If a post-dose corrected Q wave interval (QTc) interval remains ≥30 msec from the 
baseline and is >450 msec; or b) an absolute QTc value is ≥500 msec for any 
scheduled ECG for greater than 4 hours (or sooner, at the discretion of the 
investigator), or QTc intervals get progressively longer, the participant should 
undergo continuous ECG monitoring.  A cardiologist should be consulted if QTc 
intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).

In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper 
lead placement as contributing to the ECG abnormality.  It is important that leads be 
placed in the same positions each time in order to achieve precise ECG recordings.  
If a machine read QTc value is prolonged, as defined above, repeat measurements 
may not be necessary if a qualified medical provider’s interpretation determines that 
the QTc values are in the acceptable range.

ECG values of potential clinical concern are listed in Appendix 8.
8.2.5. Clinical Safety Laboratory Assessments

See Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency. Refer to Appendix 11 for monitoring and 
discontinuation criteria.

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 as per the Schedule of Activities. 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 


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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 SoA.
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.
8.2.5.1. Hepatitis Testing
Hepatitis B (HB) testing: HB surface antigen (HBsAg), HB core antibody (HBcAb), HB 
surface antibody (HBsAb), HBV DNA (where required).

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 the LLQ are excluded. Participants who have HBV DNA negative or 
below LLQ may be randomized but will have HBV DNA testing repeated at 
Week 16 and Week 26 End of Treatment (EOT) visit, or Early Discontinuation 
(ED) visit, whichever is sooner (refer to Section 7.1.). A single HBV DNA test 
result above the LLQ for a participant requires immediate and permanent 
discontinuation from treatment.
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 positive: Participant may be eligible for 
study if HBV DNA is negative or below LLQ;
HBsAg negative and HBcAb positive and HBsAb negative: Participant is excluded from 
study participation.
Hepatitis C testing: Hepatitis C virus Antibody (HCV Ab), Hepatitis C virus ribonucleic 
acid (RNA) (HCV RNA for confirmation of positive HCV Ab result).
Interpretation of Hepatitis C Testing Results:
HCV Ab positive and HCV RNA positive: Participant is excluded from study participation.


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8.2.5.2. Tuberculosis Testing
A documented TB test performed within 12 weeks prior to Day 1 (Week 0) is acceptable.  

Perform TB test procedure using the QuantiFERON-TB Gold In-Tube Test (QFT-
G).  The QFT-G may be repeated once if the investigator deems this to be necessary. 

A Purified Protein Derivative (PPD) test may be performed if the central laboratory 
is unable to determine results of QFT-G. 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.

Other TB testing may be performed at a local lab with approval from the Pfizer 
clinician.
Participants with a history of tuberculosis may not require TB testing as per the protocol 
exclusion criteria in Section 5.2. 
In addition to protocol required TB testing, a chest X-ray (or other imaging as specified in 
Section 8.2.3) is required, unless previously performed and documented within 12 weeks 
prior to Study Day 1.  Refer to Section 8.2.3.
8.2.6. Infection Studies
Blood samples will be collected per the SOA and serum isolated for infection studies; these 
samples will be analyzed only if the participant has suspected infection/reactivation where 
results are needed to assess the case. Additional sample collection instructions will be 
provided in the lab manual. The retained samples will be destroyed upon participant 
completion of this study or, if the participant enrolls in the long-term extension study, the 
samples will be destroyed upon participant completion of that study. 
8.2.7. Suicidal Ideation and Behavior Risk Monitoring

Site staff is to administer the C-SSRS to all participants at screening and score 
immediately.  Based on the judgment of the investigator, the participant must either be 
excluded or 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.

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.


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
Any lifetime history of serious or recurrent suicidal behavior (non-suicidal self-
injurous 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 ≥ 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 participant’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 must be done prior to randomization by 
a qualified MHP to determine whether it is safe for the participant to continue in the trial.  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 must 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 two 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. 
8.2.7.1. Columbia Suicide Severity Rating Scale (C-SSRS)
The Columbia Suicide Severity Rating Scale is a validated tool for investigative staff to use 
to evaluate suicidal ideation and behavior.43 Trained site staff is to administer the C-SSRS to 
all participants at screening and assess the participant’s eligibility based on the answers. 
Refer to Section 8.2.7 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 must determine 
whether an adverse event has occurred.
8.2.7.2. Patient Health Questionnaire – 8 Items (PHQ-8)
The Patient Health Questionnaire – 8 items is a participant-reported questionnaire consisting 
of 8 items to assess the participant’s depression level.44 Site staff is to administer the PHQ-8 
to all participants at screening and score immediately. Refer to Section 8.2.7 for information 
on using this tool in SIB risk monitoring.


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8.2.8. Pregnancy Testing 
For all WOCBP (refer to Appendix 4 for WOCBP definition), 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 every site visit including the follow-up visit (EOT) 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 further progress 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.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 7.  Device deficiencies are covered in Section 10.7.
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 (see Section 7).
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 


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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.
Follow up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 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 AEs and SAEs 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 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an 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/Independent Ethics 
Committees (IEC), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure (IB) and will notify the 
IRB/IEC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention(s) 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 exposure during pregnancy (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 or skin contact.
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 
preprocedure 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.


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8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the
study intervention, which may or may not lead to the occurrence of an AE. Such persons may 
include healthcare providers, family members, and other roles that are involved in the trial 
participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE. The information 
must be reported using the CT SAE Report Form,.  Since the information does not pertain to 
a participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
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
Medical devices are being provided for use in this study for the purpose of subcutaneous 
injection of dupilumab or matching placebo.  In order to fulfill regulatory reporting 
obligations worldwide, the injection administrator/trainer is responsible for the detection 
and documentation of events meeting the definitions of incident or malfunction that occur 
during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 7.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 3 of the protocol. 
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, 
and reported during all periods of the study in which the medical device is used.
If the injection administrator/trainer learns of any device deficiency at any time after a 
participant has been discharged from the study, and such incident is considered 


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reasonably related to a medical device provided for the study, the injection 
administrator/trainer will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 7.
8.3.9.2. Follow-up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The injection administrator/trainer is responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality of the 
deficiency.
New or updated information will be recorded on a follow-up form with all changes 
signed and dated by the investigator.
8.3.9.3. Prompt Reporting of Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the injection 
administrator/trainer determines that the event meets the protocol definition of a medical 
device deficiency. Information will be provided to the sponsor as described in the IP Manual.
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Sections 8.3.1.1 and 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The injection administrator/trainer will promptly report all device deficiencies occurring with 
any medical device provided for use in the study in order for the sponsor to fulfill the legal 
responsibility to notify appropriate regulatory authorities and other entities about certain 
safety information relating to medical devices being used in clinical studies.
The injection administrator/trainer, or responsible person according to local requirements (eg, 
the head of the medical institution), will comply with the applicable local regulatory 
requirements relating to the reporting of device deficiencies to the IRB/IEC.
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(s) under study may occur in clinical trial settings, such as 
medication errors.


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Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
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(s);

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating participant.
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 non-serious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of abrocitinib greater than 8 tablets within a 24-hour time period (+/-
2 hours) will be considered an overdose.  For this study, any dose of dupilumab greater than 
1 prefilled syringe every 2 weeks, with the exception of the initial loading dose of two 
prefilled syringes on Day 1, will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose of either study intervention.
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. A plasma sample for pharmacokinetic (PK) analysis may be requested by the Pfizer 
clinician (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 a SAE.


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Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
PK parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.7.2. Banked Biospecimens for Genetics
A 2 mL blood sample optimized for DNA isolation (Prep D1.5) will be collected as local 
regulations and IRBs/IECs allow.
Banked Biospecimens may be used for research related to drug response and AD. 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 Biospecimens 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 participants.  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 study manual.
8.8. Biomarkers
Biomarkers (specified analyses) are not evaluated in this study.
8.8.1. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study.
8.8.2. Specified Protein Research 
Specified protein research is not included in this study.
8.8.3. Specified Metabolomic Research 
Specified metabolomic research is not included in this study.


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8.8.4. Banked Biospecimens for Biomarkers
A 4 mL blood sample optimized for biomarkers (Prep B2.5) will be collected and isolate 
serum retained as local regulations and IRBs/IECs allow.
A 2.5 mL blood sample optimized for RNA isolation (Prep R1) will be collected as local 
regulations and IRBs/IECs allow.
Banked Biospecimens may be used for research related to the study intervention and AD. 
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 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 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.
Refer to Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the study manual.
8.9. Medical Resource Utilization and Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study with the exception of self-reported healthcare resource utilization as 
indicated in the Schedule of Activities.
9. STATISTICAL CONSIDERATIONS
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
There are two estimands for the study.
Estimand 1, composite estimand:

Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population; 

Variable: response based on achieving at least a 4-point improvement in the severity 
of PP-NRS from baseline (PP-NRS4) at Week 2; for participants who drop out for 
any reason or use rescue therapy (Section 6.5.2) at any time during the treatment 
period, the response will be defined as “non-responsive” after that point;


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
Interventional effect: Effect of randomized treatment accounting for treatment 
adherence, rescue therapy, and response; the intercurrent event (drop-out or use of 
rescue therapy) is captured through the variable definition;

Population-level summary: differences in proportions of responders between
abrocitinib and dupilumab.
Estimand 1 composite estimand is the primary estimand for the primary and key secondary 
endpoints: PP-NRS4 response at Week 2, EASI-90 at Week 4, and EASI-90 at Week 16. 
Other binary outcome measures such as response based on PP-NRS4 and EASI-90 at all 
other scheduled timepoints, EASI-75, and IGA will follow the same structure.
Estimand 2, hypothetical estimand: 

Population: Participants with moderate-to-severe Atopic Dermatitis (AD) as defined 
by the inclusion criteria to reflect the targeted participant population;  

Variable: Percent change from baseline in SCORAD at all scheduled timepoints;

Interventional effect: Effect of randomized treatment as if all participants maintain 
their randomized treatment; drop-out for any reason and use of rescue therapy are the 
intercurrent events; data after dropout or use of rescue therapy at any time during the 
treatment period will be censored;

Population-level summary: Difference in least-square means between abrocitinib and 
dupilumab.

Percent change from baseline or change from baseline to each specific post baseline 
scheduled time points in a continuous outcome measure such as HADS, POEM, 
DLQI, and EQ-5D-5L will follow the same structure as defined for SCORAD.
9.2. Sample Size Determination
This is a randomized, double-blind, double-dummy, active-controlled, multi-center study to 
assess the efficacy and safety of abrocitinib 200 mg QD compared with dupilumab (as per 
label guidelines) in adult participants on background topical therapy, with moderate to severe 
AD.  The treatment duration is 26 weeks.  A total of approximately 600 participants will be 
enrolled from approximately 220 sites globally.  There are primary efficacy assessments at 
Week 2 and Week 4, and a key secondary efficacy assessment at Week 16.  Efficacy and 
safety endpoints will be assessed throughout the entire study.


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A total sample of 600 participants, with 300 participants randomized to abrocitinib, 300 
participants randomized to dupilumab (1:1 randomization) is planned. The proposed sample 
size provides adequate power for all superiority hypotheses, as follows:
Week 2: This sample size would provide at least 99% power to detect a difference assuming 
a difference of at least 25% in PP-NRS4 between abrocitinib and dupilumab and assuming 
the dupilumab response rate is 11% at Week 2.
Week 4: This sample size will provide approximately 99% power to detect a difference 
assuming a difference of at least 15% in Week 4 EASI-90 between abrocitinib and 
dupilumab and assuming the dupilumab response rate is 12%. 
Week 16: this sample size will provide at least 99% power to show the difference is no more 
than 10% favoring dupilumab in EASI-90 at Week 16 (non-inferiority (NI) with a 10% 
margin), assuming the abrocitinib response rate is 53% and the dupilumab response rate is 
43% at Week 16. This sample size will also provide approximately 70% power to 
demonstrate superiority of abrocitinib 200 mg QD to dupilumab as measured by EASI-90 
response at Week 16.
While the power to detect a difference at the early time points of 2 and 4 weeks and non-
inferiority at week 16 is strong implying a decrease sample size could be used, the power to 
demonstrate superiority at week 16 requires the larger number of participants.  Superiority at 
week 16 is a valuable endpoint for the scientific community and prescribers justifying the 
larger sample size.  In addition, the study design avoids exposing participants to the use of 
placebo alone.  While a larger number of participants are utilized, they will be guaranteed 
treatment on 1 of the 2 active treatment arms, which allows for potential benefit for all 
participants included in the study. 
The 10% NI margin between abrocitinib and dupilumab was chosen for Week 16 EASI-90 
based on the historical data from dupilumab in treating participants with moderate to severe 
atopic dermatitis described in Section 2.2.2. Difference and the associated 95% confidence 
intervals (CIs) between dupilumab and placebo in combination therapy was 31.2% (22.9, 
39.5). The 10% NI margin preserves around two thirds of the treatment effect of dupilumab. 
Added advantages of convenient route of administration, early onset of pruritus relief, and 
unlikely development of anti-drug antibodies support that a <10% difference would not be 
considered clinically important. 
In projecting the difference between abrocitinib and dupilumab in Week 16 EASI-90 in 
combination therapy, the following assumptions were made.  Based on the monotherapy and 
combination therapy studies in the dupilumab program (Section 2.2.2), and the monotherapy 
studies in the abrocitinib program (Section 2.2.3), the projected difference between 
abrocitinib in combination with TCS and dupilumab in combination with TCS will be similar 
to the projected difference between abrocitinib and dupilumab under the monotherapy 
setting. Similar assumptions were made for Week 2 PP-NRS4 response and Week 4 EASI-
90.


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The familywise Type I error rate (for testing the primary and key secondary endpoints) will 
be strongly controlled at 5% (2-sided) using a sequential multiple testing procedure outlined 
in  Section 9.4.2.
9.3. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICD.
Randomly Assigned to 
Study Intervention
All participants who were randomly assigned to abrocitinib 
or dupilumab.
Full Analysis Set (FAS)
All randomized participants receiving at least one dose of 
study intervention. Participants will be analyzed according 
to the intervention to which they were randomized. 
Per-Protocol Analysis Set 
(PPAS)
All randomized participants receiving at least one dose of 
study intervention who had no major protocol violations.
This set will include participants 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 baseline efficacy data 
(EASI score).

Had actual, observed EASI scores at Week 16. 

Took the correct randomized treatment for at least 
80% and at most 120% of the assigned amount until 
Week 16.

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 participant and will be defined by 
the clinical team before database is locked and any 
analysis is performed for this study.
Safety
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 actually 
received.


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Unless otherwise specified, all observations after dropout or use of rescue therapy will be 
censored. For the responder analysis, data after dropout or use of rescue therapy will be 
defined as “non-responsive” after that point.
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; however, any major modifications of the primary or key secondary endpoint 
definitions or their analyses will also be reflected in a protocol amendment.
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The primary endpoints (PP-NRS4 response at Week 2, and 
EASI-90 at Week 4) will be analyzed using the Cochran Mantel 
Haenszel (CMH) test adjusted by baseline disease severity group 
(moderate and severe).  The difference between the abrocitinib 
200 mg group and the dupilumab 300 mg group in the proportion 
of participants achieving the response along with its 95% 
confidence interval (using the normal approximation for the 
difference in binomial proportions) will be reported.  The 
difference in proportions will be calculated within each 
randomization stratum.  The final estimate of the difference in 
proportions will be a weighted average of these stratum specific 
estimates using CMH weights.  This analysis is based on 
Estimand 1 composite estimand and on population defined set 
FAS. 

Secondary analysis 1: CMH test on population defined set FAS. 
This analysis will not consider the use of rescue therapy as an 
intercurrent event. For participants who drop out for any reason, 
the response will be defined as “non-responsive” after that point.

Secondary analysis 2 utilizes the longitudinal nature of the binary 
endpoint. A Generalized Linear Mixed Model (GLMM) will be 
fit to all observed data (ie, regardless of rescue therapy and 
without defining missing data as “non-response”). Under the 
missing at random (MAR) framework, imputations will be based 
on the posterior predictive probability of response obtained from 
the posterior distribution under the mixed model.  For each such 
completed dataset, the estimates of the proportions and CMH-


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Endpoint
Statistical Analysis Methods
weighted difference of proportions between abrocitinib and 
dupilumab will be obtained and Rubin’s rule will be used to 
combine the multiple estimates and standard errors across the 
imputed datasets and provide p-values.
Key 
Secondary

The non-inferiority test of the key secondary endpoint EASI-90 
at Week 16 will be analyzed using the 95% CMH weighted 
confidence interval adjusted by baseline disease severity group 
(moderate and severe). NI will be declared if the lower bound of 
the confidence interval for the response difference (abrocitinib -
dupilumab) is greater than -10%.  This analysis is based on 
Estimand 1 composite estimand and on population defined set 
FAS.

For the superiority test of the key secondary endpoint EASI-90 at 
Week 16 will be analyzed using the Cochran Mantel Haenszel 
test adjusted by baseline disease severity group (moderate and 
severe) similarly to the primary endpoints.  This analysis is based 
on Estimand 1 composite estimand and on population defined set 
FAS.

Secondary analysis 1: CMH test on population defined set PPAS. 

Secondary analysis 2: CMH test on population defined set FAS. 
This analysis will not consider the use of rescue therapy as an 
intercurrent event. For participants who drop out for any reason, 
the response will be defined as “non-responsive” after that point.

Secondary analysis 3: Missing observations will be multiply 
imputed similarly to secondary analysis 2 of the primary 
endpoints.
Secondary

The secondary endpoints which are summarized as proportions 
such as EASI-90 at Week 12, will be analyzed using the same 
method as for the primary endpoints.  This would also apply to 
any other binary endpoint in the study, such as the proportion of 
response based on IGA of clear (0) or almost clear (1) and ≥2-
point improvement from baseline. 

For continuous endpoints, a mixed effect model with repeated 
measures (MMRM) will be used.  This model will include the 
factors (fixed effects) for treatment group, disease severity group, 
visit, treatment by visit interaction, and relevant baseline value.  
Within the framework of MMRM, the treatment difference will 


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Endpoint
Statistical Analysis Methods
be tested at Week 16, as well as at the other time points by time 
point specific contrasts from the MMRM model. This analysis is 
based on Estimand 2 hypothetical estimand and on population 
defined set FAS. Observations after dropout or use of rescue 
therapy will be censored.
Exploratory
Will be described in the statistical analysis plan finalized before database 
lock.
9.4.2. Type I Error Control Procedure
The Type I error rate is set at 5% (two sided).  The familywise Type I error rate (for testing 
the primary and key secondary endpoints) will be strongly controlled at 5% using a 
sequential testing approach.  
The procedure will test all hypothesis sequentially. If one hypothesis is not rejected at the 5% 
level, then the statistical significance will be not claimed for the subsequent hypotheses 
testing. The procedure will first test superiority of PP-NRS4 response at Week 2 and then 
EASI-90 at Week 4 between abrocitinib and dupilumab by CMH test specified in the primary 
analysis. If both hypotheses are rejected, the procedure will continue to test the NI of EASI-
90 at Week 16 between abrocitinib and dupilumab. The 95% CMH weighted confidence 
interval will be constructed for the response difference and NI will be declared if the lower 
bound of the confidence interval for the response difference (abrocitinib - dupilumab) is 
greater than -10%. If the non-inferiority is achieved, the procedure will continue to test 
superiority of EASI-90 at Week 16 between abrocitinib and dupilumab by CMH test 
specified in the analysis for the key secondary endpoint.
A sequential, step-down approach with the PP-NRS4 endpoint from Week 2 to earlier time 
points will be utilized as an additional family of hypothesis tests once statistical significance 
is demonstrated at Week 2.  Specifically, further hypotheses of no difference in PP-NRS4 
between abrocitinib and dupilumab will be assessed at Day 15, Day 14, Day 13, Day 12, …, 
Day 2, in that order. Any hypotheses after the last Day for which the comparison is 
significant will not be considered statistically significant. All hypotheses in the sequence will 
be assessed at the 5% level of significance. Although this will not protect the Type-I error for 
the family of all possible comparisons, it will provide Type-I error protection for the family 
of PP-NRS4 comparisons over the first 2 weeks.
9.4.3. Safety Analyses
All participants who receive study intervention (safety population) will be included in the 
safety analyses.  All safety analyses will be performed on the Safety Population. The safety 
data will be summarized in accordance with Pfizer Data Standards. All safety data will be 


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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;

Safety laboratory tests (eg, hematology [including coagulation panel], chemistry and 
lipid profiles);

Vital signs;

ECG parameters if applicable. 
9.4.4. Other Analyse(s)
Informal interim analyses (IA) may be performed for study monitoring for internal decision-
making, due to health technology assessment requirements. The results from the IA will not 
be used to make decisions for modifying the study design or for stopping the study.  The 
conclusions with regards to the primary endpoints and the secondary endpoints will be based 
on the final analysis after study completion and hence the overall family wise Type 1 error 
for this study is maintained. Sites and participants will remain blinded to treatment 
assignment and interim results distribution will be limited.  Details will be described in a 
separate unblinding plan. 
9.5. Interim Analyses
No formal interim analysis will be performed for this study.
9.5.1. Data Monitoring Committee (DMC)
This study will use an external data monitoring committee (E-DMC).  
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. 


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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 International Council for Harmonisation (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.


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10.1.2. Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
10.1.3. Informed Consent Process

The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative 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 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 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) 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
form and will be password protected 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):  Refer to Section 9.5.1
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 participants) 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 


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(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 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 
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 participant-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.  Participant-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.


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10.1.7. Data Quality Assurance

All participant data relating to the study will be recorded on 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 form and are password protected 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 Clinical Monitoring Plan and contracts.

The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.

Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements.

Records and documents, including signed 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 


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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.
The investigator may initiate study-site closure at any time upon notification to the 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.


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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.
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 


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advice on medical questions or problems that may arise during the study.  For sites other than 
a Pfizer clinical research unit (CRU), the contact number is not intended for use by the 
participant directly, and if a participant calls that number, he or she will be directed back to 
the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 1 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 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.

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 
o
Refer to Section 5.1 Inclusion Criteria and Section 8.2.8 Pregnancy Testing for 
screening pregnancy criteria.
o
For details of timing of recommended pregnancy testing refer to the Schedule of 
Activities.
Table 1.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
Red blood cell (RBC) 
Count
Hemoglobin
Hematocrit
RBC Indices:
MCV
MCH
MCHC
RBC Morphology
Reticulocyte Count
White blood cell (WBC) count 
with Differential:
Neutrophils (%, Abs)
Lymphocytes (%, Abs)
Monocytes (%, Abs)
Eosinophils (%, Abs)
Basophils (%, Abs)
Coagulation Panel

Prothrombin 
Time/International
Normalized Ratio 
(PT/INR)
Clinical 
Chemistry1
Albumin
Alkaline 
Phosphatase
ALT
Calcium
Chloride
Creatine
GGT
Glucose (non-
fasting)
LDH
Sodium
Total CO2 (bicarbonate)
Total Protein


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Table 1.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
AST
Blood urea 
nitrogen (BUN)
Creatinine
Phosphokinase
Phosphorus
Potassium 
Total, indirect, and direct 
bilirubin
Uric Acid
Lipid Profile 
Panel2
HDL
LDL
Total Cholesterol
Triglycerides
Routine 
Urinalysis3

pH, glucose (qual), protein (qual), blood (qual), ketones, nitrites, leukocyte 
esterase by dipstick

Microscopic and/or culture examination (if blood or protein is abnormal)
Other Tests
1.
HIV4
2.
HBsAg4
3.
HBcAb4
4.
HBsAb4,5
5.
HBV DNA6
6.
HCVAb4,5
7.
HCV RNA4,5
8.
Serum Pregnancy Test7
9.
Urine Pregnancy Test7
10. QFT-G/PPD/local lab TB test (if applicable)8
11. Baseline infectionstudies (if applicable)
12. Additional infection studies (if applicable)10
13. hsCRP9
14. Lymphocyte Subsets (Lymphocyte Markers)

Total T-cells (CD3+)

CD4+ T-cells (CD3+CD4+)

CD8+ T-cells (CD3+CD8+)

NK cells (CD3-CD16+CD56+)

B-cells (CD3-CD19+)
NOTES:
1 Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Appendix 6. All events of ALT 3 × upper limit of normal (ULN) and bilirubin 2 × 
ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if INR measured 
which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis).  
2 Lipid profile panel requires at least an 8 hour fast.  
3 Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC.


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Table 1.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
4 At screening only.  HIV testing will be performed for all participants.
5 HBsAb reflex testing only if HbsAg negative but HbcAb positive. HCV RNA is reflex testing only if HCVAb is 
positive.  
6 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 LLQ will be excluded. Participants who are HBV DNA negative 
or below LLQ may be randomized and will have repeat HBV DNA testing at Week 16 and Week 26 (EOT or ED).  
7 Pregnancy testing for all WOCBP; serum FSH for confirmation of post-menopausal status.
8 PPD results should be read within 48 to 72 hours. QFT-G may be repeated once and local lab TB test may be used if 
approved by Pfizer clinician. (reference Section 8.2.5.2)
9 Results will be blinded after the screening visit.
10 Samples will be collected at each study visit for potential SARS-CoV-2 or other emergent microbial organism
testing.
Abbreviations:  cAb = core antibody ;sAb =  surface antibody; sAg = surface antigen; ALT = alanine 
aminotransferase; AST = aspartate aminotransferase; APTT = activated partial thromboplastin time; B-cell = bone 
marrow derived cell; BUN = blood urea nitrogen; CO2= carbon dioxide; CRF = case report form; hsCRP = high 
sensitivity C-reactive protein; DNA = deoxyribonucleic acid; GGT = Gamma-glutamyl transferase; HDL = high-
density lipoprotein; HBV= hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IGRA = 
interferon gamma release assay; INR = international normalized ratio; LDL =  low-density lipoprotein;  LLQ = lower 
limit of quantitation; RBC = red blood cell; LDH = lactate dehydrogenase; MCV = mean corpuscular volume ; MCH = 
mean corpuscular hemoglobin ; MCHC = mean corpuscular hemoglobin concentration ; NK = natural killer; PPD = 
purified protein derivative ; PT = prothrombin time; QFT-G = QuantiFERON-TB Gold; RNA = ribonucleic acid; TB 
= tuberculosis;  T-cell = thymus-derived cell; ULN = upper limit of normal; WBC = white blood cell; WOCBP = 
women of childbearing potential.
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. 


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


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assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE 
or SAE.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, “lack 
of efficacy” or “failure of expected pharmacological action” also constitutes 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).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 


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serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
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 Clinical Trial (CT) Serious Adverse Event 
(SAE) Report Form to Pfizer Safety.  These requirements are delineated for 3 types of 


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events: (1) SAEs; (2) non-serious adverse events (AEs); and (3) exposure to the study 
interventions  during pregnancy or breastfeeding, and occupational exposure.  
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
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 during 
pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (And exposure during 
pregnancy [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 Pfizer Safety /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.


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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an 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 Pfizer Safety. 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 
Pfizer Safety.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.


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
If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for 
reporting purposes, as defined by the sponsor" and "In addition, if the 
investigator determines that an SAE is associated with study procedures, the 
investigator must record this causal relationship in the source documents and 
CRF, and report such an assessment in the dedicated section of the CT SAE 
Report Form and in accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Pfizer 
Safety to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
post-mortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the Pfizer Safety within 24 
hours of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.


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
Contacts for SAE reporting can be found in the investigator site file.
SAE Reporting to Pfizer Safety via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to Pfizer Safety.

In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.

Contacts for SAE reporting can be found in the investigator site file.


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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is 100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), as described below, during the intervention period 
and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s).  If a highly effective method that is user dependent is 
chosen, a second effective method of contraception, as described below, must also 
be used.  The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
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. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy


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For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
NOTE: Documentation for any of the above categories 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.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, a

high follicle stimulating hormone (FSH) level in the postmenopausal 
range must be used to confirm a postmenopausal state in women under 60 
years of age not using hormonal contraception or hormonal replacement 
therapy (HRT).

female on HRT and whose menopausal status is in doubt will be required 
to use one of the nonestrogen hormonal highly effective contraception 
methods if they wish to continue their HRT during the study. Otherwise, 
they must discontinue HRT to allow confirmation of postmenopausal 
status before study enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed.  If not, an additional highly effective 
method of contraception should be used.  The spermatogenesis cycle is 
approximately 90 days.


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6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;

Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
In addition, one of the following effective barrier methods must also be used when 
option 6 or 7 are chosen above:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).


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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 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 (refer to Section 8.7.2 and Section 8.8.4) 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 
ULN should be monitored more frequently to determine if they are an “adaptor” or are 
“susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
o
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
o
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
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 Hepatic 


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Injury Council (HIC) should be informed if such a situation occurs during the study; the HIC 
will provide the necessary support to the study teamThe participant should return to the 
investigator site and be evaluated as soon as possible, preferably within 48 hours from 
awareness of the abnormal results.  This evaluation should include laboratory tests, detailed 
history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s Law, additional laboratory tests should include albumin, creatine kinase (CK), direct 
and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time 
(PT)/international normalized ratio (INR), total bile acids, and alkaline phosphatase. 
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) and collection of serum sample for acetaminophen drug and/or protein 
adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the 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: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with ISO 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (refer to Section 6.1.2 for the list of sponsor 
medical devices).
10.7.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory finding) in study 
participants, users, or other persons, whether or not related to the investigational 
medical device.  This definition includes events related to the investigational 
medical device or comparator for study participants, users, and other persons.  This 
definition also includes events considered related to procedures for study 
participants only.

An ADE is defined as an adverse event related to the use of an investigational 
medical device.  This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device 
as well as any event resulting from use error or from intentional misuse of the 
investigational medical device.
10.7.2. Definition of SAE, SADE, and Unanticipated Serious Adverse Device Effect
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).


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An SAE is an AE that:
a. Led to death. 
b.
Led to serious deterioration in the health of the participant, that either resulted in:

A life-threatening illness or injury.  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, that hypothetically might have caused 
death, if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

An SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
USADE Definition

A USADE is a serious adverse device effect which by its nature, incidence, 
severity, or outcome has not been identified in the current version of the risk 
analysis management file.
10.7.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance.  Device deficiencies 
include malfunctions, use errors, and inadequate labeling.


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10.7.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the injection 
administrator/trainer to review all documentation (eg, hospital progress notes, 
laboratory reports, and diagnostic reports) related to the event.

The injection administrator/trainer will then record all relevant AE/SAE/device 
deficiency information in the participant’s medical records, in accordance with the 
investigator’s normal clinical practice and on the appropriate form of the CRF.

It is not acceptable for the injection administrator/trainer to send photocopies of the 
participant’s medical records to Pfizer Safety in lieu of following the reporting 
process described in the IP Manual.

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.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.


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
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/device deficiency.

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 product information, for marketed products, 
in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency 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 an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

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/SAE/device deficiency as 
fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.


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
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 
postmortem 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.
10.7.5. 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.

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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10.7.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.


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10.8. Appendix 8: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events (AEs)

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by 60 msec from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm.

New-onset type I second-degree (Wenckebach) atrioventricular (AV) block of >30 
seconds’ duration.

Frequent premature ventricular complexes (PVCs), triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events (SAEs)

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:
In awake, symptom-free participants in sinus rhythm, with documented periods of 
asystole 3.0 seconds or any escape rate <40 beats per minute (BPM), or with 
an escape rhythm that is below the AV node; 
In awake, symptom-free participants with atrial fibrillation and bradycardia with 1 
or more pauses of at least 5 seconds or longer; 
Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 BPM) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).


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
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate 
<40 BPM), accelerated idioventricular rhythm (40< x <100), and 
monomorphic/polymorphic ventricular tachycardia >100 BPM (such as torsades de 
pointes).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events

Change in pattern suggestive of new myocardial infarction. 

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.


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10.9. Appendix 9: Diagnostic Criteria for Atopic Dermatitis
Per Inclusion Criterion 2, a participant is to have a clinical diagnosis of atopic dermatitis 
according to the criteria of Hanifin and Rajka.21
Hanifin and Rajka’s Diagnostic Criteria for Atopic Dermatitis
Must have 3 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 3 or more following minor features:
Xerosis
Ichthyosis/palmar hyperlinearity, keratosis pilaris
Immediate (type 1) skin test reaction
Elevated serum Immunoglobulin E (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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10.10. Appendix 10: Prohibited Concomitant Medications which may result in Drug-
Drug Interaction (DDI)
The prohibited concomitant medications listed below should not be taken with abrocitinib for 
the period of time listed below.  
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
After consulting with the sponsor, the investigator will make a judgement on the ongoing 
participation of any participant with prohibited medication use during the study.
This list of drugs prohibited for potential DDI concerns with the study intervention may be 
revised during the course of the study with written notification from sponsor, to include or 
exclude specific drugs or drug categories for various reasons (e.g., emerging DDI results for 
the study intervention, availability of new information in literature on the DDI potential of 
other drugs).
This is not an all-inclusive list.  Site staff should consult with the sponsor or designee with 
any questions regarding potential DDI.
Drug Category 
Drugs
Required Washout Period 
requirement
CYP2C9 Inhibitors
amiodarone
fluconazole
fluvoxamine
miconazole
oxandrolone 
voriconazole 
1 week
or
5 half-lives
whichever is longer
CYP2C19 Inhibitors
esomeprazole
fluconazole
fluoxetine
fluvoxamine
isoniazid
moclobemide
omeprazole
ticlopidine
voriconazole
1 week
or
5 half-lives
whichever is longer
CYP2C9 Inducers
carbamazepine 
enzalutamide 
rifampicin
5 half-lives plus 14 days
For example, 
carbamazepine:
The average half-life of 
carbamazepine after repeat 
dosing is on average 15 
hours, so 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.
CYP2C19 Inducers
enzalutamide 
rifampicin
5 half-lives plus 14 days


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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, for a total of approximately 80 days prior to the first dose of study 
intervention.
Investigators should consult the dupilumab product label for information regarding 
medication that is prohibited for concomitant use. 
Investigators should consult the product label for any other medication used during the study 
for information regarding medication that is prohibited for concomitant use.


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10.11. Appendix 11: Monitoring and Discontinuation Criteria
This appendix documents the monitoring and discontinuation criteria for this study that, in 
rare instances, may be extenuating circumstances that might mitigate the need for 
discontinuation that can be discussed with the medical monitor.
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 the baseline 
value and is also below the lower limit of normal; 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
An investigator can temporarily interrupt oral study intervention for up to a maximum of 28 
consecutive days and up to 2 consecutive doses of injectable study intervention for a 
participant, for safety reasons or while monitoring abnormal laboratory tests if the 
investigator judges that this is necessary.  In the case of study intervention being withheld, all 
study interventions that the participant is receiving should be withheld (ie, both oral and 
injected study interventions).  The investigator should use their judgement with regard to 
unscheduled visits/laboratory/clinical assessments required to monitor the participant during 
this timeframe.  If within this timeframe the investigator judges that it is safe to restart 
dosing, then the participant may restart study intervention.  If the investigator judges that it is 
not safe to restart dosing within this timeframe then the participant must be permanently 
discontinued from treatment, have an End of Treatment visit and enter the 4-week follow-up 
period (See Section 10.12.3 for UK country-specific requirements).  Doses not taken for the 
reasons mentioned above do not constitute protocol deviations or medication errors and 
should not be considered dosing errors but should be noted in the dosing log with the reason 
for reduced drug consumption clearly described.


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Discontinuation Criteria
Participants must be permanently discontinued from treatment if they meet any of the 
following criteria at any point in the study:

Participants who have recurrent suicidal ideation and behavior (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 
two 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. 

Marked prolongation of the QTcF interval to >500 ms or >60 ms change from 
screening ECG (refer to Appendix 8). 

Serious infection (refer to 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 unless discussed and agreed 
with the medical monitor. If the participant cannot be restarted on study intervention 
within 28 days or the infection is not resolved, or there is no agreement received from 
the medical monitor then the participant must be permanently discontinued. 

Any bleeding event thought to be associated with a platelet count or hemoglobin 
reduction per the judgement of the investigator (or, if necessary/desired, following 
discussion with the medical monitor).

Adverse event, per judgment of the investigator, requiring discontinuation from 
treatment (or, if necessary/desired, following discussion with the medical monitor).

Any adverse event or laboratory abnormality, that per the investigator’s judgement 
requires withholding of oral study intervention for >28 consecutive days and > 2 
consecutive doses of injectable study intervention.
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 or <30% from baseline value.

Two sequential increases in serum creatinine that are >50% over the average of 
screening and baseline values AND an absolute increase in serum creatinine 


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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.

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 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 LFT findings should prompt review of Appendix 6 (Liver Safety) 
for which additional investigations must be conducted.
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 
(See Section 10.12.3 for UK country-specific instructions). 
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 their judgment of safety concerns.  Unscheduled laboratory testing through 
the central laboratory may be obtained at any time during the study to assess such concerns. 
If a participant has a clinically significant, treatment emergent, abnormality at the time of 
withdrawal from the study, the Pfizer medical monitor (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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10.12. Appendix 12: Country-specific Requirements
10.12.1. France Contrat Unique
1. GCP Training
Before enrolling any participants, the investigator and any sub-investigators will 
complete the Pfizer-provided Good Clinical Practice training course (“Pfizer GCP 
Training”) or training deemed equivalent by Pfizer. Any investigators who later join 
the study will complete the Pfizer GCP Training or equivalent before performing 
study-related duties. For studies of applicable duration, the investigator and sub-
investigators will complete Pfizer GCP Training or equivalent every 3 years during 
the term of the study, or more often if there are significant changes to the ICH GCP 
guidelines or course materials.
2. Study Intervention
No participants or third-party payers will be charged for study intervention.
3. SUSARs.
Pursuant to a sponsor’s safety reporting obligations under 21 CFR 312.32(c)(1), 
Pfizer will report to the Investigator all Serious Unexpected Suspected Adverse 
Reactions (“SUSARs”). Investigator will receive and review SUSAR reports and 
report SUSARs to the responsible IRB/IEC according to institution’s guidelines.
4. Collection of ethnic origin information
Information regarding ethnic origin will be collected in this study in compliance with 
the French Data Protection Authority, Commission nationale de l'informatique et des 
libertés (CNIL): Deliberation no. 2016-262 of 21 July 2016 amending the reference 
methodology for the processing of personal data conducted in connection with 
biomedical research (MR-001), §2.2.3 Nature of the data.
individuals participating in this study will consent that this information can be 
collected in the study before they enter the study.
The electronic Case Report Form (eCRF) will be used as the source file for ethnic 
origin in France. This information will not be recorded in the participant’s medical 
records.
5. Termination Rights
Pfizer retains the right to discontinue development of abrocitinib at any time.+


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10.12.2. Czech Republic Country-specific Requirements
Participants receiving topical or systemic rescue therapy must be permanently discontinued 
from the study intervention, have an End of Treatment visit, and enter the 4-week follow-up 
period.
10.12.3. United Kingdom Country-specific Requirements
WOCBP in the UK who do not rollover into the long-term extension study (B7451015) will 
have a follow-up visit 4 weeks after the ED/EOT visit and have a follow-up phone call at 12 
weeks after the ED/EOT visit to confirm adherence to contraception guidelines per protocol.


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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 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 eDiary for completion, including the participant’s understanding of the daily 
completion requirements;

Review accelerometry and arrange for return of used devices and sending of new 
devices, if applicable.

Complete contraceptive check and results of pregnancy testing. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. Refer 
to Appendix 4 regarding pregnancy tests.

Administer the C-SSRS and follow-up as necessary per protocol Section 8.2.7.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
10.13.2. Home health visits
A home health care service may be utilized 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 8.4.


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
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

PROs

Vital sign measurements

Review eDiary for completion, including the participant’s understanding of the daily 
completion requirements;

Review accelerometry and arrange for return of used devices and sending of new 
devices, if applicable.

Complete contraceptive check and results of pregnancy testing. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. Refer 
to Appendix 4 regarding pregnancy tests.

Administer the C-SSRS and follow-up as necessary per protocol Section 8.2.7.
10.13.3. Alternative Facilities for Safety Assessments
10.13.3.1. Laboratory testing
Protocol-specified safety laboratory tests may be performed by in-home visit (e.g. home 
phlebotomy service), where allowable by law or local guidance, if the study participant is 
unable to visit the local laboratory utilized by the study site. There must (at a minimum) be a 
record of verbal consent of the participant or, as applicable for minor participants, a record of 
verbal consent of the participant’s legally authorized representative including whether they 
consent to provide their personal information to the 3rd party vendor for this purpose and 
verbal assent of the study participant.
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible.  The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should 
be recorded on the CRF. 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 IU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records. Confirm that the participant is adhering to the contraception 
method(s) required in the protocol. 
If the safety of a participant is at risk because they cannot complete required evaluations
or adhere to critical mitigation steps, then potential temporary interruption or permanent
discontinuation of that participant from study intervention must be discussed with the
sponsor. A benefit-risk judgment by the investigator, agreed with the sponsor, will
ultimately be required.


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10.13.3.2. Electrocardiograms
If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must order, 
receive, and review results.
10.13.4. 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.
Examples of potentially acceptable delivery methods (not an all-inclusive list): 

Site staff delivery with confirmation of temperature monitoring and time in transit 
(time study intervention leaves site until delivered to participant);

Site courier with confirmation of temperature monitoring and time in transit (time 
study intervention is picked up at site until delivered to participant. There must (at a 
minimum) be a record of verbal consent of the participant, including whether they 
consent to provide their personal information to a 3rd party vendor for this purpose. 
Note: If no temperature monitoring is available, assess and document if average 
temperature in the geographic area is within the stability range, anticipating shipping 
transit times and possible travel delays – and ensure to discuss this further with the 
sponsor.
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 event (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 efficacy assessments may be assessed by a qualified rater and PROs administered on the 
tablet may be completed as part of a home health care visit but cannot be completed as part 
of a TeleHeath visit.  


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10.13.7. Data monitoring committee
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.


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10.14. Appendix 14: Abbreviations
Abbreviation
Term
AAD
American Academy of Dermatology
Ab
antibody
ACQ
Asthma Control Questionnaire
AD
atopic dermatitis
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AV
atrioventricular
BBS
Biospecimen Banking System
BCG
Bacille Calmette Guérin
BP
blood pressure
BPM
beats per minute
BSA
body surface area
CAFÉ
A Study to Assess the Efficacy and Safety of Dupilumab in 
Patients with Severe Atopic Dermatitis (AD) That Are Not 
Controlled with Oral Cyclosporine A (CSA) or for Those Who 
Cannot Take Oral CSA Because it is Not Medically Advisable
CD
cluster of differentiation
CFB
change from baseline
CFR
Code of Federal Regulations
CHRONOS
Study to Assess the Efficacy and Long-term Safety of 
Dupilumab (REGN668/SAR231893) in Adult Participants with 
Moderate-to-Severe Atopic Dermatitis
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CNIL
Commission nationale de l'informatique et des libertés
CO2
carbon dioxide
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease of 2019
CK
creatine kinase
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CsA
cyclosporine A
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
DDI
Drug-drug interaction
DILI
drug-induced liver injury
DLQI
Dermatology Life Quality Index


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Abbreviation
Term
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
eDiary
electronic diary
ED
early discontinuation
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EOS
End of Study
EOT
End of Treatment
EQ-5D-3L
EuroQol Quality of Life 5-Dimension 3-Level Scale
EQ-5D-5L
EuroQol Quality of Life 5-Dimension 5-Level Scale
EU
European Union
EudraCT
European Clinical Trials Database
FACS
fluorescence-activated cell sorting
FAS
full analysis set
FDA
Food and Drug Administration 
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLMM
generalized linear mixed model
HADS
Hospital Anxiety and Depression Scale
HB
hepatitis B
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBcAb 
hepatitis B core antibody
HBV
hepatitis B virus
HCRU
Healthcare Resource Utilization
HCV
hepatitis C virus
HDL
high-density lipoprotein 
HEENT
head, eyes, ears, nose and throat
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormonal replacement therapy
hsCRP
high-sensitivity C-reactive protein
HTA
health technologies assessment 
IA
Interim Analysis
IB
Investigator’s Brochure


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Abbreviation
Term
ICD
informed consent document
ICF
informed consent form
ICH
International Council for Harmonisation
ID
identification
IEC
independent ethics committee
IFN
interferon
IFN-
interferon-gamma
IGA
Investigator’s Global Assessment
IgE 
Immunoglobulin E
IL
interleukin
INR
international normalized ratio
IP Manual
Investigational Product Manual
IRB
institutional review board
IRT
interactive response technology
IWR
interactive Web-based response
JAK
Janus kinase
JAK1
Janus kinase 1
JAK2
Janus kinase 2
JAK3
Janus kinase 3
LDH
lactate dehydrogenase
LDL
low-density lipoprotein
LFT
liver function test
LLQ
lower limit of quantification
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
MMRM
mixed-effect model with repeated measures
MOS
medical outcomes study
MTX
methotrexate
NB-UVB
narrowband ultraviolet B light
NI 
non-inferiority
OTC
over the counter
NRS 
numerical rating scale
PACL
Protocol Administrative Change Letter
PCD
primary completion date
PDE4
phosphodiesterase 4
PEER 
Pediatric Eczema Elective Registry 
PFS
prefilled syringe
PHQ-8
Patient Health Questionnaire - 8 items
PK
Pharmacokinetic(s)


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Abbreviation
Term
PP-NRS
Peak Pruritus Numerical Rating Scale
PP-NRS
Peak Pruritis Numerical Rating Scale 4
POC
proof of concept
POEM
Patient-Oriented Eczema Measure
PPAS
per-protocol analysis set
PPD
purified protein derivative 
PRO
patient reported outcome
PSAAD
Pruritus and Symptoms Assessment for Atopic Dermatitis
PT
prothrombin time
PVC(s)
premature ventricular complex(es)
QD
once daily
QFT-G
QuantiFERON-TB Gold
QoL
quality of life
QT
Q wave interval
QTc
corrected Q wave interval
QTcF
Fridericia corrected Q wave interval
QW
weekly
Q2W
every two weeks
RBC
red blood cell
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCORAD
SCORing atopic dermatitis
SIB
suicidal ideation and behavior
SoA
schedule of activities
SOC
system organ class
SOLO 1
Study of Dupilumab Monotherapy Administered to Adult 
Patients with Moderate-to-Severe Atopic Dermatitis
SOLO 2
Study of Dupilumab Monotherapy Administered to Adult 
Patients with Moderate-to-Severe Atopic Dermatitis
SOP
standard operating procedure
SP-NRS
Skin Pain Numerical Rating Scale
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBili
total bilirubin
TCI
topical calcineurin inhibitors
TCS
topical corticosteroids
TH1
type 1 helper T cell
TH2
type 2 helper T cell
TYK2
tyrosine kinase 2
UK
United Kingdom


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Abbreviation
Term
ULN
upper limit of normal
US
United States
USPI
United States Package Insert
UVA
ultraviolet A light
UVB
ultraviolet B light
VAS
visual analog scale
VTE
venous thromboembolism
WASO
wake after sleep onset
WBC
white blood cell
WOCBP
woman of childbearing potential


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54. Juniper EF, O'Byrne PM, Guyatt GH, et al. Development and validation of a 
questionnaire to measure asthma control. Eur Respir J 1999; 14: 902–7.
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2005; 99:553-58.

SAP_001.pdf: 
Protocol B7451050 (PF-04965842) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 1
Protocol B7451050
A PHASE 3B RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, ACTIVE 
CONTROLLED MULTI-CENTER STUDY ASSESSING THE EFFICACY AND 
SAFETY OF ABROCITINIB COMPARED WITH DUPILUMAB IN ADULT 
PARTICIPANTS ON BACKGROUND TOPICAL THERAPY WITH MODERATE 
TO SEVERE ATOPIC DERMATITIS
Statistical Analysis Plan 
(SAP)
Version:
2
Date: 21 Jul 2021




































































Protocol B7451050 (PF-04965842) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 35
9. APPENDICES
Appendix 1. Summary of Efficacy Analyses
Endpoint
Analysis Type
Population
Data Inclusion and Rules for Handling 
Intercurrent Events and Missing Data 
Analysis Model
Week 2 PP-NRS4 Response
Main analysis
FAS with 
baseline 
PP-NRS 
൒4
For participants who drop out for 
any reason or use rescue therapy, the 
response will be defined as “non-
responsive” after that point.
CMH
Sensitivity/supplementary 
analysis
FAS with 
baseline 
PP-NRS 
൒4
For participants who drop out for 
any reason, the response will be 
defined as “non-responsive” after 
that point.
CMH
Sensitivity/supplementary 
analysis
FAS with 
baseline 
PP-NRS 
൒4
All observations will be used; 
missing values will be handled 
through multiple imputations.
CMH
Week 4 EASI-90 Response
Main analysis
FAS 
For participants who drop out for 
any reason or use rescue therapy, the 
response will be defined as “non-
responsive” after that point.
CMH
Sensitivity/supplementary 
analysis
FAS 
For participants who drop out for 
any reason, the response will be 
defined as “non-responsive” after 
that point.
CMH


Protocol B7451050 (PF-04965842) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 36
Endpoint
Analysis Type
Population
Data Inclusion and Rules for Handling 
Intercurrent Events and Missing Data 
Analysis Model
Sensitivity/supplementary 
analysis
FAS 
All observations will be used; 
missing values will be handled 
through multiple imputations.
CMH
Week 16 EASI-90 Response
Main analysis
FAS 
For participants who drop out for 
any reason or use rescue therapy, the 
response will be defined as “non-
responsive” after that point.
CMH
Sensitivity/supplementary 
analysis
PPAS
For participants who drop out for 
any reason or use rescue therapy, the 
response will be defined as “non-
responsive” after that point.
CMH
Sensitivity/supplementary 
analysis
FAS 
For participants who drop out for 
any reason, the response will be 
defined as “non-responsive” after 
that point.
CMH
Sensitivity/supplementary 
analysis
FAS 
All observations will be used; 
missing values will be handled 
through multiple imputations.
CMH
Weeks 2, 4, 8, 12, 16, 20 and 
26 Percent Change from 
Baseline in %BSA
Main analysis
FAS 
Data after dropout or use of rescue 
therapy will be set as missing; only 
observed data will be used.
MMRM
Time from baseline to 
achieve at least a 4-point 
Main analysis
FAS with 
baseline 
PP-NRS observations will first be 
censored by use of rescue therapy; 
for all participants who have not 
Time to Event


Protocol B7451050 (PF-04965842) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 37
Endpoint
Analysis Type
Population
Data Inclusion and Rules for Handling 
Intercurrent Events and Missing Data 
Analysis Model
improvement in the severity 
of PP-NRS scale
PP-NRS 
൒4
experienced the event, their time to 
event will be right censored at the 
last available measurement time.
Medicated Topical 
Background Therapy-Free 
days
Main analysis
FAS
The intercurrent event is captured 
through endpoint definition. Missing 
dates will be imputed by Pfizer 
standards.
ANCOVA
CMH=Cochran-Mantel-Haenszel; ANCOVA=Analysis of Covariance; MMRM=Mixed-effect Model Repeated Measures; TP=Tipping Point.
PP-NRS4 Response at all other scheduled timepoints will follow the main analysis of Week 2 PP-NRS4 Response. Other binary 
endpoints will follow the main analysis of Week 4 EASI-90 Response.
Other percent change from baseline or change from baseline to each specific post baseline scheduled time points in a continuous 
outcome measure will follow the main analysis of Weeks 2, 4, 8, 12, 16, 20 and 26 Percent Change from Baseline in %BSA.