A RANDOMIZED, OPEN-LABEL, PARALLEL-GROUP STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ABROCITINIB 100 MG AND 200 MG TABLETS IN PARTICIPANTS AGED 12 YEARS AND OLDER WITH MODERATE TO SEVERE ATOPIC DERMATITIS IN INDIA
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Pfizer



Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 2
Document History
Document 
Version Date
Amendment 1
23 March 2022
Original Protocol
21 December 2021
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any protocol administrative 
clarification letter.
Protocol Amendment Summary of Changes Table
Amendment 1 (23-March-2022)
Overall Rationale for the Amendment: This protocol is being amended to reflect 
recommendations from India BoH: to revise protocol into Phase 3; to add SCORAD 
assessment; to indicate that photography should be utilized to capture the AD lesions.  
Detailed changes are summarized below in a tabular form.
Section # and Name
Description of Change
Brief Rationale

Cover Page
Revision of study phase 
from 3b/4 to 3
Per India BoH’s recommendation

Section 1.1 
(Synopsis);

Section 1.3 (SoA);

Section 3 (Objectives, 
endpoints and 
estimands);

Section 8.1.4 
(SCORAD, Newly 
Added);

Section 9.1.1.2 
(Secondary 
Estimands);

Section 9.3.3 
(Secondary Endpoint 
Analysis)

Section 10.9 
(Abbreviations)
Added SCORAD 
efficacy assessment for 
atopic dermatitis as a 
secondary endpoint
Per India BoH’s recommendation

Section 1.3 (SoA)

Section 8.1.2 (IGA)

Section 8.1.3 (EASI)
Added Photography in 
SoA
Added 1 new section 
for Photography;
Per India BoH’s recommendation

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 3
Section # and Name
Description of Change
Brief Rationale

Section 8.1.6 
(Photography, Newly 
Added)
Removed text from 
Sections 8.1.2 and 
8.1.3: “Photographic 
images of the lesion 
will be taken as part of 
source documentation, 
wherever possible.”

Section 1.3 (SoA);

Section 10.10.2 
(Substudy SoA)
Added contraception 
check at each visit
Updates in SoA and substudy SoA

Section 8.2.5 Clinical 
Safety Laboratory 
Assessments 

Section 10.2 
(Appendix 2: Clinical 
Laboratory Tests);

Section 10.10.2 
(Substudy SoA);

Section 10.10.7.2 
(Substudy Early 
Termination/End of 
Treatment Visit)
Added laboratory tests 
at EoT visit of the 
substudy.
Updated substudy SoA 
and relevant sections.
Updates in substudy SoA and 
relevant sections

Section 10.10.2 
(Substudy SoA)
Added text in time 
frame for substudy 
follow-up visit
Updates in substudy SoA for 
clarity

Section 1.3 (SoA)
Added Weight 
measurement at
Baseline
Updates in SoA

Section 10.10.2 
(Substudy SoA)
Added vital signs 
measurement at all 
visits
Updates in substudy SoA

Section 1.1 (Synopsis)

Section 9.4 (Interim 
Analysis)

Section 10.10.10.4 
(Substudy Interim 
Analysis)
Added text: 
As this is an open-label 
study, the sponsor may 
conduct reviews of the 
data, including MRI 
data, (newly added)
during the course of the 
study for the purpose of 
safety assessment or to 
support regulatory 
To clarify on interim analysis, and 
further define the range and 
purpose of data review

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 4
Section # and Name
Description of Change
Brief Rationale
submissions (newly 
added).
There will be no formal
(newly added) interim 
analysis for this 
substudy.  The sponsor 
may conduct reviews 
of the data, including 
MRI data, during the 
course of the study for 
the purpose of safety 
assessment or to 
support regulatory 
submissions (newly 
added).

Section 9.3.3 
(Secondary Endpoint 
Analysis)
Added text: 
“Descriptive statistics 
for change from 
baseline in POEM and 
ADCT scores will be 
derived at all scheduled 
timepoints, for each 
treatment arm.”
To clarify on secondary PRO 
endpoint analysis

Section 1.1 (Synopsis)

Section 2.3 
(Benefit/Risk 
Assessment)

Section 3 (Objectives, 
Endpoints, and 
Estimands)

Section 4.1 (Overall 
Design)

Section 10.10.1.1 
(Substudy Background 
and Rationale)

Section 10.10.3 
(Substudy Objectives 
and Endpoints)

Section 10.10.4 
(Substudy Design)
Revised “Abnormal 
developmental bone 
findings related to study 
intervention”, 
“abnormal bone 
findings”, “abnormal 
findings” in knee MRI-
related sections to
“Bone safety findings”
To correct an editorial error and 
keep consistency with the program 
objective

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 5
Section # and Name
Description of Change
Brief Rationale

Section 10.10.8.1 
(Bone Safety Findings 
Identified in Central 
Evaluation of Knee 
MRI Images)

Section 10.10.10.3 
(Substudy Safety 
Analyses)
Minor editorial changes throughout the document.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 6
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schema ....................................................................................................................16
1.3. Schedule of Activities .............................................................................................17
2. INTRODUCTION ...............................................................................................................20
2.1. Study Rationale .......................................................................................................20
2.2. Background .............................................................................................................20
2.2.1. Atopic Dermatitis........................................................................................20
2.2.2. Clinical Efficacy and Safety of Abrocitinib ...............................................21
2.3. Benefit/Risk Assessment.........................................................................................24
2.3.1. Risk Assessment.........................................................................................25
2.3.2. Benefit Assessment.....................................................................................27
2.3.3. Overall Benefit/Risk Conclusion................................................................27
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................27
4. STUDY DESIGN.................................................................................................................28
4.1. Overall Design.........................................................................................................28
4.2. Scientific Rationale for Study Design.....................................................................29
4.2.1. Safety Adjudication Committee .................................................................29
4.2.2. Choice of Contraception/Barrier Requirements .........................................29
4.3. Justification for Dose ..............................................................................................29
4.4. End of Study Definition ..........................................................................................30
5. STUDY POPULATION......................................................................................................30
5.1. Inclusion Criteria.....................................................................................................30
5.2. Exclusion Criteria....................................................................................................31
5.3. Lifestyle Considerations..........................................................................................34
5.3.1. Meals and Dietary Restrictions...................................................................35
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................35
5.3.3. Vaccine and Exposure to Infections Guidelines.........................................35
5.3.3.1. Participant Specific Recommendations.....................................35
5.3.4. Contraception..............................................................................................35

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 7
5.4. Screen Failures ........................................................................................................35
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................36
6.1. Study Intervention(s) Administered........................................................................36
6.1.1. Administration............................................................................................36
6.2. Preparation, Handling, Storage, and Accountability...............................................37
6.2.1. Preparation and Dispensing........................................................................38
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................38
6.3.1. Allocation to Study Intervention ................................................................38
6.4. Study Intervention Compliance...............................................................................38
6.5. Dose Modification...................................................................................................39
6.6. Continued Access to Study Intervention After the End of the Study......................39
6.7. Treatment of Overdose............................................................................................39
6.8. Concomitant Therapy..............................................................................................40
6.8.1. Permitted Concomitant Treatments............................................................41
6.8.2. Prohibited Medications and Treatments .....................................................41
6.8.3. Rescue Medicine.........................................................................................41
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................42
7.1. Discontinuation of Study Intervention ....................................................................42
7.2. Participant Discontinuation/Withdrawal From the Study.......................................43
7.2.1. Withdrawal of Consent...............................................................................44
7.3. Lost to Follow-Up ...................................................................................................44
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................44
8.1. Efficacy Assessments..............................................................................................46
8.1.1. Rater Qualifications....................................................................................46
8.1.2. IGA .............................................................................................................46
8.1.3. EASI ...........................................................................................................47
8.1.3.1. BSA Efficacy.............................................................................49
8.1.4. SCORAD....................................................................................................50
8.1.5. PROs...........................................................................................................51
8.1.5.1. PP-NRS .....................................................................................51
8.1.5.2. POEM........................................................................................51

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 8
8.1.5.3. ADCT........................................................................................51
8.1.6. Photography................................................................................................52
8.2. Safety Assessments .................................................................................................52
8.2.1. Physical Examinations................................................................................52
8.2.2. Vital Signs ..................................................................................................52
8.2.3. Chest X-Ray................................................................................................53
8.2.4. Electrocardiograms.....................................................................................53
8.2.5. Clinical Safety Laboratory Assessments ....................................................53
8.2.6. Pregnancy Testing ......................................................................................54
8.2.7. Knee MRI ...................................................................................................54
8.2.8. Suicidal Ideation and Behavior Risk Monitoring.......................................54
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................55
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......55
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................56
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................56
8.3.2. Method of Detecting AEs and SAEs ..........................................................56
8.3.3. Follow-Up of AEs and SAEs......................................................................56
8.3.4. Regulatory Reporting Requirements for SAEs...........................................57
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................57
8.3.5.1. Exposure During Pregnancy......................................................57
8.3.5.2. Exposure During Breastfeeding ................................................59
8.3.5.3. Occupational Exposure .............................................................59
8.3.6. Cardiovascular and Death Events...............................................................59
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................59
8.3.8. Adverse Events of Special Interest.............................................................59
8.3.8.1. Lack of Efficacy........................................................................60
8.3.9. Medical Device Deficiencies......................................................................60
8.3.10. Medication Errors.....................................................................................60
8.4. Pharmacokinetics ....................................................................................................61
8.5. Genetics...................................................................................................................61
8.5.1. Specified Genetics ......................................................................................61

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 9
8.6. Biomarkers ..............................................................................................................61
8.7. Immunogenicity Assessments.................................................................................61
8.8. Health Economics ...................................................................................................61
9. STATISTICAL CONSIDERATIONS ................................................................................61
9.1. Statistical Hypotheses .............................................................................................61
9.1.1. Estimands....................................................................................................61
9.1.1.1. Primary Estimand......................................................................61
9.1.1.2. Secondary Estimands ................................................................62
9.2. Analysis Sets ...........................................................................................................63
9.3. Statistical Analyses .................................................................................................63
9.3.1. General Considerations...............................................................................64
9.3.2. Primary Endpoint Analysis.........................................................................64
9.3.3. Secondary Endpoint Analysis.....................................................................64
9.4. Interim Analyses .....................................................................................................64
9.5. Sample Size Determination.....................................................................................64
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................65
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............65
10.1.1. Regulatory and Ethical Considerations ....................................................65
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................65
10.1.2. Financial Disclosure .................................................................................66
10.1.3. Informed Consent Process ........................................................................66
10.1.4. Data Protection .........................................................................................68
10.1.5. Committees Structure ...............................................................................69
10.1.5.1. Data Monitoring Committee ...................................................69
10.1.6. Dissemination of Clinical Study Data ......................................................69
10.1.7. Data Quality Assurance ............................................................................70
10.1.8. Source Documents....................................................................................71
10.1.9. Study and Site Start and Closure ..............................................................72
10.1.10. Publication Policy...................................................................................72
10.1.11. Sponsor’s Qualified Medical Personnel .................................................73
10.2. Appendix 2: Clinical Laboratory Tests .................................................................74

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 10
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................75
10.3.1. Definition of AE .......................................................................................75
10.3.2. Definition of an SAE ................................................................................76
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Colletion Period..............................................................................77
10.3.4. Reporting of SAEs....................................................................................81
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................83
10.4.1. Male Participant Reproductive Inclusion Criteria....................................83
10.4.2. Female Participant Reproductive Inclusion Criteria.................................83
10.4.3. Woman of Childbearing Potential ............................................................83
10.4.4. Contraception Methods.............................................................................84
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments .......86
10.6. Appendix 6: ECG Findings of Potential Clinical Concern ...................................88
10.7. Appendix 7: Prohibited Concomitant Medications That May Result in DDI.......90
10.8. Appendix 8: Alternative Measures During Public Emergencies ..........................92
10.8.1. Telehealth Visits.......................................................................................92
10.8.2. Alternative Facilities for Safety Assessments ..........................................93
10.8.2.1. Laboratory Testing ..................................................................93
10.8.2.2. Electrocardiograms..................................................................93
10.8.3. Study Intervention ....................................................................................93
10.8.4. Adverse Events and Serious Adverse Events...........................................94
10.9. Appendix 9: Abbreviations ...................................................................................95
10.10. Appendix 10: An Imaging Substudy for Evaluation of Abrocitinib’s 
Potential Effects on Adolescent Bone in Participants With Moderate to Severe 
AD in India................................................................................................................98
10.10.1. Substudy Introduction.............................................................................98
10.10.1.1. Substudy Background and Rationale ....................................98
10.10.2. Substudy Schedule of Activities...........................................................100
10.10.3. Substudy Objectives and Endpoints .....................................................102
10.10.4. Substudy Design...................................................................................102
10.10.5. Substudy Eligibility Criteria.................................................................103
10.10.5.1. Substudy Inclusion Criteria.................................................103

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 11
10.10.5.2. Substudy Exclusion Criteria................................................104
10.10.5.3. Substudy Enrollment Criteria..............................................104
10.10.5.4. Substudy Lifestyle Requirements........................................104
10.10.6. Substudy Study Treatments ..................................................................104
10.10.7. Substudy Study Procedures ..................................................................104
10.10.7.1. Substudy Screening/Enrollment and Initial Knee MRI 
Evaluation........................................................................................104
10.10.7.2. Substudy Early Termination/End of Treatment Visit .........105
10.10.7.3. Substudy Follow-up Visit....................................................106
10.10.7.4. Substudy Discontinuation Criteria ......................................106
10.10.7.5. Substudy Participant Withdrawal........................................106
10.10.8. Substudy Assessments..........................................................................106
10.10.8.1. Bone Safety Findings Identified in Central Evaluation 
of Knee MRI Images .......................................................................107
10.10.8.2. Patient-Report Outcomes for the SubStudy ........................108
10.10.9. Substudy AE Reporting........................................................................108
10.10.9.1. Withdrawal From the Substudy Due to AEs.......................108
10.10.10. Substudy Data Analysis/Statistical Methods......................................109
10.10.10.1. Sample Size Determination...............................................109
10.10.10.2. Substudy Efficacy Analysis ..............................................109
10.10.10.3. Substudy Safety Analyses .................................................109
10.10.10.4. Substudy Interim Analysis ................................................109
10.10.11. Substudy Safety Adjudication Committees........................................109
11. REFERENCES ................................................................................................................110

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 12
LIST OF TABLES
Table 1.
IGA Scores................................................................................................47
Table 2.
Clinical Sign Severity Scoring Criteria for the EASI...............................48
Table 3.
Handprint Determination of BSA.............................................................48
Table 4.
EASI Area Score Criteria .........................................................................49
Table 5.
EASI Body Region Weighting .................................................................49
Table 6.
Protocol-Required Safety Laboratory Assessments .................................74

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 13
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: A randomized, open-label, parallel-group study to evaluate the safety and 
efficacy of abrocitinib 100 mg and 200 mg tablets in participants aged 12 years and older 
with moderate to severe atopic dermatitis in India
Brief Title: A Safety and Efficacy Study of Abrocitinib Tablets in Participants Aged 12 
Years and Older with Atopic Dermatitis in India
Rationale: 
The causes of AD are varied. Both a genetic predisposition and numerous trigger factors play 
an important role in the first manifestation and in exacerbations of the disease.
As per the Indian consensus statement for management of AD, patients with AD suffer from 
dry skin and defective skin barrier function, that manifests mainly as pruritus. Systemic 
therapy is used to treat patients with moderate to severe AD on failure of topical treatments. 
Currently approved systemic agents in India have modest efficacy in patients with moderate 
to severe AD but are associated with adverse events that often limit long-term use. 
Abrocitinib is an oral, once daily JAK1 selective inhibitor under investigation for the 
treatment of moderate to severe AD. Selective inhibition of JAK1 with abrocitinib modulates 
signaling by IL-4, IL-13, and other cytokines (eg, IL-31, IL-22, and TSLP) involved in the 
pathogenesis of AD and pruritus while sparing JAK2 inhibition and minimizing the risk for 
neutropenia and anemia. Inhibition of neuronal JAK1 dependent pathways has also been 
shown to ameliorate pruritus.1
This study is planned to provide additional safety and efficacy data for abrocitinib in India.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 14
Objectives, Endpoints, and Estimands
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary:
To evaluate the safety of 
abrocitinib in participants aged 12 
years and older with moderate to 
severe AD.
Incidence of AEs and SAEs.
The primary estimand for safety 
is the incidence of AEs and SAEs 
in participants aged 12 years and 
older with moderate to severe 
AD, from the time of first dose to 
Week 16, regardless of dosing 
compliance or treatment 
discontinuation.
Secondary: 
Secondary:
Secondary: 
To assess the efficacy of 
abrocitinib in participants aged 12 
years and older with moderate to 
severe AD.

Response based on IGA score 
of clear (0) or almost clear (1) 
and greater than or equal to 2 
points improvement from 
baseline at Week 12.

Response based on achieving 
≥75% improvement from 
baseline in the EASI total score 
(EASI-75) at Week 12.

Response based on ≥75% 
improvement in SCORAD 
(SCORAD75) at Week 12.

Change from baseline in POEM 
at Week 12 and at all scheduled 
time points.

Change from baseline in ADCT 
at Week 12 and at all scheduled 
time points.
The secondary estimand is the 
treatment effect of abrocitinib on 
participants aged 12 years and 
older with moderate to severe 
AD, based on IGA response, 
EASI-75 response and 
SCORAD75 response from 
baseline to Week 12, considering 
patients who discontinued 
treatment as non-responders and 
based on outcome measures of 
POEM and ADCT from baseline 
to Week 12 and at all scheduled 
time points. Data collected after 
treatment discontinuation is 
excluded.
Primary substudy objective(s):
Primary substudy endpoint (as 
secondary endpoints for 
B7451094):
Primary substudy estimand(s):
To evaluate the potential effects 
of abrocitinib on bone 
development in adolescent 
participants 12 to <18 years of 
age, as assessed by knee MRI.
The proportion of bone safety 
findings in knee MRI 1 year after 
randomization in adolescent 
participants exposed to 
abrocitinib 100 mg and 200 mg 
QD.
The primary substudy estimand is 
the incidence of bone safety 
findings in knee MRI after 1 year 
of being exposed to abrocitinib in 
adolescent participants 12 to <18 
years of age, regardless of dosing 
compliance or treatment 
discontinuation.
Overall Design
Brief Summary
This is a randomized, open-label, parallel-group study to assess the safety and efficacy of 
orally administered tablets of abrocitinib 100 mg and 200 mg QD in participants aged 12 
years and older with moderate to severe AD in India. There is a planned treatment duration 
of 12 weeks, with 4 weeks of off-treatment safety follow up thereafter. Study participants 
will be screened within 28 days prior to the first dose of study intervention to confirm that 
they meet the eligibility criteria for the study. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 15
This study protocol also includes a substudy evaluating whether abrocitinib has any potential 
effects on adolescent bone with regard to bone safety findings in knee MRI. Adolescent 
participants (12 to <18 years of age) will continue to receive study intervention until 1 year 
after randomization into the main study. Section 10.10 (Appendix 10) contains complete 
information regarding the substudy.
Number of Participants
Approximately 200 participants will be enrolled and randomized to study intervention at 
approximately 10 sites in India. Adolescent participants 12 to <18 years of age will be 
enrolled in the knee MRI substudy. 
Intervention Groups and Duration
Participants who meet eligibility criteria at baseline will be randomized in a 1:1 ratio to 
receive abrocitinib 200 mg in tablet form (100 mg tablet × 2) (n=100) or abrocitinib 100 mg 
(100 mg tablet × 1) (n=100) taken once daily by mouth. The total treatment duration will be 
12 weeks with a 4-week off-treatment safety follow-up period for the main study, and 1 year 
treatment period for adolescent participants enrolled in the knee MRI substudy. 
Data Monitoring Committee or Other Independent Oversight Committee: Yes
Safety Adjudication Committees:
To independently assess the specific, complex safety events related to malignancies, 
cardiovascular events, and opportunistic infections (including eczema herpeticum and other 
infections of special interest) in this study, Safety Adjudication Committees, consisting of 
clinical experts in each of the relevant clinical areas, will be set up to harmonize and 
standardize assessments. In order to allow for an unbiased safety assessment, the members of 
these committees will be blinded to treatment assignment. Further information about the 
Safety Adjudication Committees will be defined 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. A separate safety adjudication committee will be established for the MRI 
substudy for bone findings.
Statistical Methods
A sample of 200 participants (100 randomized participants per treatment arm) would allow 
estimation of the incidence rate of any AE with maximum margin of error of 10%, in each 
treatment arm. All randomized participants who receive at least 1 dose of abrocitinib will be 
included in the analyses. The number and percentage of treatment-emergent AEs will be 
summarized according to type, frequency, severity, seriousness and relationship to 
abrocitinib in each treatment arm. The response rates, together with the corresponding 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 20
2. INTRODUCTION
Abrocitinib is a JAK1 inhibitor that is being investigated as a treatment for patients with AD. 
Abrocitinib is an orally bioavailable small molecule that selectively inhibits JAK1 by 
blocking the ATP binding site and has a high degree of selectivity for JAK1 when compared, 
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-5, IL-13, IL-22, IL-31, 
TSLP, and IFN-γ.
2.1. Study Rationale 
Abrocitinib is currently being developed as a novel treatment for AD. Data from phase 3 
studies (B7451012, B7451013, B7451014, B7451029, B7451036, B7451050) that evaluated 
abrocitinib 100 mg and 200 mg in patients with moderate to severe AD reported statistically 
significant improvement in efficacy endpoints in both treatment groups compared to the 
placebo group with an acceptable safety profile. The purpose of the study is to provide 
additional safety and efficacy data for abrocitinib in India.
2.2. Background
2.2.1. Atopic Dermatitis
AD, also known as atopic eczema, is a chronic, relapsing inflammatory skin condition 
characterized by dry, pruritic skin lesions which can affect any part of the body. Distribution 
and morphology of AD skin lesions are distinguishably different between pediatric and adult 
populations 2,3 with lesions in infants occurring mainly on the face and extensor surfaces of 
limbs, while adolescents/adults often present with lichenified and excoriated plaques at 
flexures, and with involvement of the head, neck, upper trunk, shoulders, and scalp. The 
lifetime prevalence of AD in children is 10%-20% with 70% of cases occurring in children 
<5 years of age. Most cases (approximately 75%) improve by adulthood, while 
approximately 25% of AD patients have symptoms throughout their life. Key cytokines 
implicated in the pathophysiology of AD including IL-4, IL-5, IL-13, IL-22, IL-31, and 
IFN-, require JAK1 for signal transduction, suggesting 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.4
AD affects up to 25% of children and 2%-4% of adults worldwide.5 Research suggests that 
approximately 17% of adolescents and 58% of adults with AD have moderate-to-severe 
disease,6,7 the burden of which is multidimensional. For example, persons with 
moderate-to-severe AD experience sleep disturbances, physical pain, and psychological 
distress.8 In addition to disease-related atopic comorbidities, those with moderate-to-severe 
AD also experience greater health care resource utilization and incur significant economic 
burdens when compared with non-AD controls.9

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 21
As per the Indian consensus statement for management of AD, patients with AD suffer from 
dry skin and defective skin barrier function, that manifests mainly as pruritus. Systemic 
therapy is used to treat patients with moderate to severe AD on failure of topical treatments. 
Current immunosuppressive agents have modest efficacy in patients with moderate-to-severe 
AD but are associated with AEs that often limit long-term use. 
2.2.2. Clinical Efficacy and Safety of Abrocitinib
Abrocitinib is being developed as an oral treatment for patients with moderate to severe AD 
based on unmet need for an effective oral systemic treatment for moderate-to-severe AD with 
a manageable safety profile, its novel mechanism of action, and the clinical results obtained 
in Phase 1, Phase 2, and Phase 3 studies. Selective inhibition of JAK1 with abrocitinib 
modulates signaling by IL-4, IL-13, and other cytokines (eg, IL-31, IL-22, and TSLP) 
involved in the pathogenesis of AD and pruritus while sparing JAK2 inhibition and 
minimizing the risk for neutropenia and anemia. Inhibition of neuronal JAK1 dependent 
pathways has also been shown to ameliorate pruritus.1
Phase 2b in AD
B7451006 was a Phase 2b POC trial in 269 adults (ages 18-75) with moderate-to-severe AD 
investigating doses of abrocitinib 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 patients 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 changes from baseline 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. 
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 Pruritus 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 Pruritus NRS score).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 22
Abrocitinib appeared generally safe and well tolerated in this study. Overall, AEs and SAEs 
were numerically higher in participants receiving abrocitinib compared to placebo, but did 
not appear to increase with dose. The most common AEs were in the SOCs of infections and 
infestations, skin and subcutaneous tissue disorders and gastrointestinal disorders, and the 
majority of the AEs were mild. There were 2 cases of herpes zoster, one in the 10 mg group 
(not treatment related), and one in the 30 mg group (treatment related). There were dose 
dependent decreases in platelet counts observed in the study, which plateaued at Week 4. 
Further details of the clinical Phase 2 development program can be found in the IB.
Phase 3 in AD
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).
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% 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 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 23
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 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 AEs was 
higher in the abrocitinib group compared with the placebo group. The proportion of 
participants experiencing SAEs and severe AEs was similar across all treatment arms. The 
discontinuation rates due to an AE were low in each treatment arm compared to placebo.
B7451014 was a randomized, responder-enriched, double-blind, placebo-controlled, Phase 3 
dosing regimen study to evaluate the efficacy and safety of abrocitinib monotherapy in 
participants aged 12 years and older with chronic moderate to severe AD as defined per the 
inclusion criteria and a body weight ≥40 kg. The study met its primary endpoint (ie, 
assessment of loss of response requiring rescue treatment during the blinded treatment 
period). By Week 52, participants in each abrocitinib group had a significantly higher 
probability of not flaring compared to placebo. Abrocitinib was well tolerated. The observed 
safety events were consistent with those seen in other abrocitinib studies.
Two Phase 3 studies evaluated 100 mg and 200 mg of abrocitinib in combination with topical 
medicated therapy. Study B7451029 in adults evaluated abrocitinib in context with 
dupilumab for 16 weeks in a double-blind, double-dummy design. Both doses were 
statistically superior to placebo with respect to the co-primary endpoint of IGA 0-1 and 
EASI-75, and met the key secondary endpoint showing a statistically significant difference 
from dupilumab in the relief of itch. Study B7451036 evaluated abrocitinib 100 mg and 
200 mg QD in a 12-week, double-blind placebo-controlled fashion in adolescents, and 
showed similar results as those observed in adolescents from the monotherapy studies. Both 
doses met the co-primary endpoints of IGA and EASI-75 responses at Week 12 and the 
200 mg dose met the key secondary endpoint showing statistically significantly greater 
proportions of PP-NRS4 responders compared with the placebo group at Weeks 2, 4, and 12. 
Safety results show that both doses of abrocitinib were well-tolerated, and there were no 
unexpected safety events. The discontinuation rates due to an AE were low in both 
abrocitinib treatment arms (5.8% for both 100 mg and 200 mg) compared to placebo (9.1%). 
The B7451050 study has evaluated abrocitinib 200 mg QD in a head to head manner 
compared with dupilumab in adult participants. Both primary endpoints were met; abrocitinib 
200 mg QD was clinically and statistically superior to dupilumab at Week 2 in regard to 
proportion of PP-NRS4 responders and at Week 4 with regard to proportion of EASI-90 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 24
responders. Additionally, the prespecified and error controlled key secondary endpoint was 
met; abrocitinib 200 mg QD is clinically and statistically superior to dupilumab in regard to 
proportion of responders at Week 16 attaining EASI-90.
2.3. Benefit/Risk Assessment
There was clinically meaningful benefit demonstrated with abrocitinib in the Phase 2b POC 
study (B7451006) in adult participants with moderate to severe AD and the completed 
Phase 3 studies (B7451012, B7451013, B7451014, B7451029, B7451036, B7451050). 
Similar benefit-risk profile has been observed in adolescents with AD. The potential risks of 
treatment include those that were noted in Phase 2b and Phase 3 studies and those based on 
the pharmacology of JAK inhibitors and include venous thromboembolism, 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. 
An abrocitinib-related long bones finding was observed in repeat-dose short duration (up to 
1 month) toxicity studies in young rats. This microscopic finding of bone dystrophy that was 
noted in young rats is not expected to pose a risk in patients ≥12 years of age at clinically 
relevant therapeutic doses and exposures. This is because the microscopic long bones finding 
was considered reversible, nonprogressive, and the NOEL exposure margin at which no bone 
finding was noted was at least 6 × the unbound human AUC at the maximum clinical dose of 
200 mg QD (the bone finding was noted at ≥23×). No abrocitinib-related clinical 
observations, macroscopic, or microscopic, by histopathological examination, long bones 
findings were observed in rats at any dose in the 6-month toxicity study (up to 26 × the 
unbound human AUC at the maximum clinical dose of 200 mg QD) or in young or adult 
monkeys in any of the toxicity studies up to 9 months in duration (up to 31 × the unbound 
human AUC at the maximum clinical dose of 200 mg QD). The doses used in rats exceeded 
the relevant human equivalent exposures. In addition, young monkey is a sensitive 
nonclinical species for the detection of potential effects on bone growth and development 
relevant to adolescent humans (Section 10.10) and no adverse effects on bone were found in 
monkeys. The risk-benefit for adolescents to participate in this study remains favorable. The 
preclinical findings indicate a low risk of potential effects in human adolescents, however, in 
order to fully investigate this possibility, a substudy has been added to this protocol 
(Appendix 10) to evaluate whether abrocitinib has any potential effects on bone with regard 
to bone safety findings in knee MRI in adolescent participants with moderate to severe AD in 
India. 
Appropriate risk evaluation and mitigation strategies have been incorporated into this 
protocol.
Overall, there is a favorable benefit-risk profile to support the continued development of 
abrocitinib in the treatment of 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 AEs of abrocitinib is provided in the IB, which is the SRSD for this study.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 25
2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s) Abrocitinib
1) Serious infection and opportunistic infections are 
a potential risk of abrocitinib.
1) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
1) Participants with acute and chronic skin 
infections, history of specific recurrent infections 
and/or latent infections will be excluded from the 
study including participants with evidence of 
active, latent, or inadequately treated infection 
with Mycobacterium TB. Participants with a 
known immunodeficiency disorder will be 
excluded. Through regular clinic visits, the 
investigator will closely monitor the participant for 
the development of signs and symptoms of 
infection during study participation. Participants 
who develop serious infections will be evaluated 
for potential discontinuation.
2) Viral reactivation is a potential risk of abrocitinib.
2) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
2) Participants known to be infected with HIV, 
Hepatitis B, or Hepatitis C are excluded from 
study. Participants with a history of disseminated 
herpes zoster or disseminated herpes simplex are 
excluded from the study. 
3) Malignancy and lymphoproliferative disorders.
3) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
3) Participants who 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 will be excluded. At 
regular clinic visits, the investigator will complete 
skin examinations.
4) Decreased lymphocyte counts.
4) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
4) Participants with an absolute lymphocyte count 
of <0.50 × 109 /L (<500/mm3) will be excluded 
from the study. Lymphocyte counts will be 
monitored throughout the study via laboratory 
assessments. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 26
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s) Abrocitinib
5) Decreased platelet counts. 
5) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
5) Participants with any of the following will be 
excluded from the study: platelet counts of <150 ×
109/L (<150,000/mm3); current or past medical 
history of conditions associated with 
thrombocytopenia, coagulopathy, or platelet 
dysfunction. Additionally, platelet counts will be 
monitored throughout the study.
6) Alterations in lipid profile.
6) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
6) Investigators will monitor lipid profiles in 
participants throughout the study. 
7) Venous thromboembolism.
7) The potential risk has been reported for other 
JAK inhibitors. Refer to the IB for more 
information.
7) Participants with an increased risk of 
developing VTE will be excluded from the study 
and discontinued if they develop VTE or become 
high risk for VTE during study treatment. 
8) DDI risk with medications that are strong 
inhibitors and inducers of CYP2C9 and CYP2C19 
enzymes.
8) The risk is based on results of DDI studies. 
Refer to the IB for more information.
8) Concomitant use of inhibitors and inducers of 
CYP2C9 and CYP2C19 enzymes is not allowed in 
the study.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 27
2.3.2. Benefit Assessment
All adolescent and adult participants in this study will receive treatment with abrocitinib 
(100 mg and 200 mg QD) which has previously demonstrated efficacy and an acceptable 
safety profile in Phase 3 studies and has been approved for the treatment of moderate to 
severe AD in Great Britain and Japan. It is possible that a study participant’s AD symptoms 
may improve during treatment with abrocitinib, but there is no guarantee of benefit. 
Participants may also benefit from protocol participation by gaining knowledge about their 
health status through study tests (eg, physical examinations, laboratory assessments, vital 
sign measurements) conducted at regular intervals during the trial.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants in this study, the 
potential risks identified in association with abrocitinib are justified by the anticipated 
benefits that may be afforded to participants with moderate to severe AD who have 
inadequate treatment options. The study will collect safety and efficacy data in a population 
representative of those who will receive the study intervention if approved by regulatory 
authorities.
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary:
To evaluate the safety of 
abrocitinib in participants aged 12 
years and older with moderate to 
severe AD.
Incidence of AEs and SAEs.
The primary estimand for safety is 
the incidence of AEs and SAEs in 
participants aged 12 years and 
older with moderate to severe AD, 
from the time of first dose to 
Week 16, regardless of dosing 
compliance or treatment 
discontinuation.
Secondary: 
Secondary:
Secondary: 
To assess the efficacy of 
abrocitinib in participants aged 12 
years and older with moderate to 
severe AD.
Response based on IGA score of 
clear (0) or almost clear (1) and 
greater than or equal to 2 points 
improvement from baseline at 
Week 12.
Response based on achieving ≥75% 
improvement from baseline in the 
EASI total score (EASI-75) at 
Week 12.
Response based on ≥75% 
improvement from baseline in 
SCORAD (SCORAD75) at Week 12.
Change from baseline in POEM at 
Week 12 and at all scheduled time 
points.
Change from baseline in ADCT at 
Week 12 and at all scheduled 
timepoints.
The secondary estimand is the 
treatment effect of abrocitinib on 
participants aged 12 years and 
older with moderate to severe AD, 
based on IGA response, EASI-75 
response and SCORAD75 
response from baseline to 
Week 12, considering patients 
who discontinued treatment as 
nonresponders and based on 
outcome measures of POEM and 
ADCT from baseline to Week 12 
and at all scheduled timepoints. 
Data collected after treatment 
discontinuation is excluded.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 28
Objectives
Endpoints
Estimands
Primary substudy objective(s):
Primary substudy endpoint (as 
secondary endpoints for B7451094):
Primary substudy estimand(s):
To evaluate the potential effects of 
abrocitinib on bone development 
in adolescent participants 12 to 
<18 years of age, as assessed by 
knee MRI.
The proportion of bone safety 
findings in knee MRI 1 year after 
randomization in adolescent 
participants exposed to abrocitinib 
100 mg and 200 mg QD.
The primary substudy estimand is 
the incidence of bone safety 
findings in knee MRI after 1 year 
of being exposed to abrocitinib in 
adolescent participants 12 to <18 
years of age, regardless of dosing 
compliance or treatment 
discontinuation.
4. STUDY DESIGN
4.1. Overall Design
This is a randomized, open-label, parallel-group study to assess the safety and efficacy of 
orally administered tablets of abrocitinib 100 mg and 200 mg QD in participants aged 12 
years and older with moderate to severe AD in India. A total of approximately 
200 participants will be enrolled from approximately 10 sites in India. Approximately 200 
participants will be randomly assigned to study intervention. Safety endpoints will be 
assessed throughout the entire study. Secondary efficacy assessments are conducted from 
Screening to EOT visit. 
After providing informed consent or, for minor age participants, informed consent of the 
legally authorized representative (parent/guardian) and assent of the study participant, 
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 or intolerance to treatment with 
medicated topical therapy for at least 4 weeks or must have required systemic therapies for 
control of their disease. 
Eligible participants must meet the eligibility criteria at baseline. Participants who meet 
eligibility criteria at baseline will undergo Day 1 assessments and be randomized in a 1:1 
ratio to receive abrocitinib 200 mg QD or abrocitinib 100 mg QD in an open-label fashion. 
The total treatment period is 12 weeks. All participants will undergo a 4week offtreatment 
safety follow-up period thereafter. 
This study protocol also includes a substudy evaluating whether abrocitinib has any potential 
effects on adolescent bone with regard to bone safety findings in knee MRI. All adolescent 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 29
participants 12 to <18 years of age will continue to receive study intervention until 1 year 
after randomization in the main study. Section 10.10 (Appendix 10) contains complete 
information regarding the substudy. 
For study estimands, refer to Section 3.
4.2. Scientific Rationale for Study Design
This study will investigate the safety and efficacy of abrocitinib in participants with moderate 
to severe AD in Indian population if approved by the India regulatory authority, as India was 
not part of the global trials. This study is designed to specifically evaluate abrocitinib in 
participants 12 years of age or older with AD in India. 
4.2.1. Safety Adjudication Committee
To facilitate standardization of assessments within the abrocitinib program, a safety event 
adjudication committee of independent clinical experts will assess malignancies, 
cardiovascular events, and opportunistic infections (including eczema herpeticum and other 
infections of special interest) in this study. A separate adjudication committee will be 
established for the MRI substudy to evaluate bone-related events.
Events requiring review may be identified by the Pfizer study team or designee during the 
review of participant data listings or monitors during routine monitoring of 
participants’ study records. The Pfizer study team or designee will notify relevant 
investigators of any events identified. Investigators will be responsible for obtaining and 
submitting the documentation to be reviewed by the safety event adjudication 
committee. Documentation includes, but is not limited to, hospital progress notes, laboratory 
reports, and diagnostic reports. These documents may be reviewed by Pfizer.
Further information about this safety event adjudication committee is provided in a charter, 
including a description of the scope of the committee’s responsibilities, the process and 
definitions to be utilized by the committee for adjudication, and communication plan 
including timelines.
Additional safety event adjudication committees may be established during the study to 
standardize additional safety event assessments. As described above, individual committee 
charters will provide specific descriptions of the scope of responsibilities and the processes 
and definitions used to assess specific safety events.
4.2.2. Choice of Contraception/Barrier Requirements
Human reproductive safety data are not available for abrocitinib, but there is no suspicion of 
human teratogenicity based on the intended pharmacology of the compound. Therefore, the 
use of a highly effective method of contraception is required for WOCBP (see Appendix 4).
4.3. Justification for Dose
Dose selection for Phase 3 was based on efficacy and safety of abrocitinib from a 
dose-ranging Phase 2b study, B7451006 that evaluated a 20-fold dose range (10 mg to 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 30
200 mg QD) in adults with AD. The 200 mg QD dose is expected to provide efficacy similar 
to that of currently approved systemic treatments in moderate-to-severe AD, and was 
therefore selected as the high dose for evaluation in Phase 3 studies. An additional dose of 
100 mg QD was also selected for evaluation in Phase 3, since this dose is expected to provide 
clinical efficacy in IGA response, while differentiating from the higher dose in terms of 
expected efficacy and systemic exposure. Both 100 mg and 200 mg QD doses demonstrated 
acceptable safety and tolerability in the Phase 2 study, and the 200 mg dose also 
demonstrated acceptable safety and tolerability in the completed Phase 3 studies (B7451012 
and B7451013). Further details are available in the IB. Both abrocitinib 100 mg and 200 mg 
QD doses have been approved for the treatment of moderate to severe AD in Great Britain 
and Japan, for adults and adolescents. Indian patients are not expected to have altered PK or 
altered response to the drug. 
4.4. End of Study Definition
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 SoA for the last participant in the trial.
Participants are considered to have completed the study if they have completed all periods of 
the study, including the last visit or the last scheduled procedure shown in the SoA.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants must be of 12 years of age or older, at the time of informed consent.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Meet all the following AD criteria:

Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 1 year 
prior to Day 1 and has confirmed AD (Hanifin and Rajka criteria of AD10).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 31

Moderate to severe AD (affected BSA ≥10%, IGA ≥3, EASI ≥16, and PPNRS ≥4 
at the baseline visit);

Documented recent history (within 6 months before the screening visit) of 
inadequate response to treatment with topical medications for at least 4 weeks, or 
for whom topical treatments are otherwise medically inadvisable (eg, because of 
important side effects or safety risks), or who have required systemic therapies for 
control of their disease.
3. Negative pregnancy test for females of childbearing potential at Screening. Female 
participants of childbearing potential must agree to use a highly effective method of 
contraception for the duration of the active treatment period and for at least 28 days 
after the last dose of study intervention. 
Weight:
4. Body weight ≥25 kg at Baseline.
Informed Consent:
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol. Evidence of a personally signed and dated ICD indicating that the 
participant (or a legally acceptable representative, parent(s)/legal guardian) has been 
informed of all pertinent aspects of the study. For minors under the age of legal 
consent in India, assent of the participating child needs to be documented for the age 
range 12 to 18 years in addition to the parental informed consent. 
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Currently have active forms of other inflammatory skin diseases or have evidence of 
skin conditions (eg, psoriasis, seborrheic dermatitis, lupus).
2. A current or past medical history of conditions associated with thrombocytopenia, 
coagulopathy or platelet dysfunction or QT interval abnormalities.
3. Have increased risk of developing venous thromboembolism, eg, deep vein 
thrombosis or pulmonary embolism:

History of venous thromboembolism, or

First degree relative with unprovoked venous thromboembolism (ie, 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 (eg, Factor V Leiden).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 32
4. Have a history of any lymphoproliferative disorder such as EBV related 
lymphoproliferative disorder, history of lymphoma, leukemia, or signs or symptoms 
suggestive of current lymphatic or lymphoid disease.
5. Past history or active infection with Mycobacterium TB, disseminated herpes zoster 
or disseminated herpes simplex, HIV, Hepatitis B, or Hepatitis C.
6. 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.
7. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgement, make the participant 
inappropriate for the study. Any psychiatric condition including recent or active 
suicidal ideation or behavior that met any of the following criteria when screened for 
during the main study:

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; 

The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria;

In the opinion of the investigator or Pfizer (or designee) exclusion is required.
Prior/Concomitant Therapy:
8. Prior treatment with systemic JAK inhibitors.
9. Participants who are vaccinated with live attenuated vaccine within the 6 weeks prior 
to the first dose of abrocitinib or who are expected to be vaccinated with these 
vaccines during treatment or during the 6 weeks following discontinuation of 
abrocitinib.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 33
10. Have received any of the following treatment regimens specified in the timeframes 
outlined below: 
Within 1 year of first dose of study intervention:

Prior treatment with non B cell-specific lymphocyte depleting agents/therapies 
(eg, 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 CD 19/20+ counts by FACS analysis.
Within 12 weeks of first dose of study intervention: 

Biologic drugs that have immunomodulatory properties or could be used to treat 
AD: within 12 weeks of first dose of investigational product or 5 half-lives (if 
known), whichever is longer.
Other biologics without immunomodulatory properties (eg, insulin) are permissible at 
the judgement of the Investigator. 
Within 4 weeks of first dose of study intervention: 

Use of oral immunosuppressive drugs (eg, CsA, azathioprine, methotrexate, 
systemic corticosteroids, mycophenolate-mofetil, IFN-) within 4 weeks of first 
dose of study intervention or within 5 half-lives (if known), whichever is longer. 
NOTE: Systemic corticosteroids must be discontinued before Study Day 1, but a 
specific timeframe for discontinuation prior to first dose of abrocitinib is not required. 
NOTE: Corticosteroid inhalers and intranasal sprays are permissible. 
NOTE: Ophthalmic corticosteroids are permissible.
Within 1 week of first dose of study intervention: 

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.
11. Require treatment with prohibited concomitant medication(s) or have received a 
prohibited concomitant medication.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 34
Prior/Concurrent Clinical Study Experience:
12. Participation in other studies involving investigational drug(s) or vaccine within 8 
weeks or within 5 half-lives (if known) whichever is longer, prior to study entry 
and/or during study participation.
Diagnostic Assessments:
13. Any of the following abnormalities in clinical laboratory tests at Screening:

Absolute neutrophil count of 1.0 × 109/L (1000/mm3);

Platelet count of 150 × 109/L (150,000/mm3);

Absolute lymphocyte count of <0.50 × 109/L (500/mm3);

Estimated Creatinine Clearance 60 mL/min using the CockcroftGault method;

AST or ALT values 2 times the ULN;

TBili ≥1.5 times the ULN. 
Other Exclusions:
14. Pregnant or breastfeeding women, or women of childbearing potential who are 
unwilling to use highly effective contraception consistently and correctly for the 
entire duration of the study and for at least 28 days after the last dose of study 
intervention.
15. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 
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 clinical assessments are performed before dose is administered.
2. On study visit days, showering or bathing is permitted prior to attending the study 
visit, but participants must not moisturize or apply emollient.
3. On study visit days, topical therapies (ie, non-medicated topical therapy and 
medicated topical therapy, per protocol guidelines as described in Section 6.8.2) 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 6.8.1).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 35
5.3.1. Meals and Dietary Restrictions
On study visit days as per the SoA participants should comply with fasting requirements for 
at least 8 hours prior to the visit, if possible. Water and permitted non-study medications are 
allowed (Section 6.8.1).
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). This includes 
approved/emergency use authorization COVID-19 vaccinations. Vaccination of participants 
with live attenuated vaccine is prohibited within the 6 weeks prior to first dose of abrocitinib, 
during treatment with abrocitinib, and during the 6 weeks following discontinuation of 
abrocitinib. Routine inactivated or other types of vaccines are allowed before and during the 
study.
5.3.4. Contraception
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 Section 10.4.4) 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) 
considering that their risk for pregnancy may have changed since the last visit. 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.
5.4. 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/enrolled in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the CONSORT publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if they fail the screening evaluation for reasons related to incidental transitory 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 36
conditions. Individuals for whom screen failure is related to failing the disease severity 
(including extent of disease) inclusion criterion and who subsequently experience worsening 
AD, which in the investigator’s judgement would make them eligible for participation, may 
be considered for re-screening. Such cases should be discussed with the Pfizer Medical 
Monitor (or designee) to determine if re-screening is appropriate.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to abrocitinib.
6.1. Study Intervention(s) Administered
Study Intervention
Intervention Name
Abrocitinib
Abrocitinib
ARM Name
Abrocitinib 200 mg QD
Abrocitinib 100 mg QD
Type
Small molecule
Small molecule
Dose Formulation
Tablet
Tablet
Unit Dose Strength
100 mg
100 mg
Dosage Level
100 mg x 2 tablets
100 mg x 1 tablet
Route of Administration
Oral
Oral
Sourcing
Provided centrally by the 
Sponsor
Provided centrally by the 
Sponsor
Packaging and Labeling
Study Intervention will be 
provided in bottles. Each bottle 
will be labeled as required per 
country requirement.
Study Intervention will be 
provided in bottles. Each bottle 
will be labeled as required per 
country requirement.
Study Arms
Arm Title
Abrocitinib 200 mg QD
Abrocitinib 100 mg QD
Arm Type
Experimental
Experimental
Arm Description
Participants will receive 
abrocitinib 200 mg QD for 12 
weeks.
Participants will receive 
abrocitinib 100 mg QD for 12 
weeks.
Associated Intervention Labels
Abrocitinib
Abrocitinib
6.1.1. Administration
Orally administered study intervention, abrocitinib 100 mg tablet(s), will be administered QD 
from Day 1 to Week 12. Participants will be dispensed bottles of study intervention at Day 1, 
Week 2, Week 4 and Week 8 visits. Study intervention administration details for substudy 
participants is mentioned in Section 10.10 (Appendix 10).
Participants will be given clear dosing instructions to take either 1 tablet or 2 tablets of study 
intervention once daily by mouth with meals, preferably in the morning whenever possible, 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 37
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. If the participant experiences nausea, might consider 
administering the oral study intervention at night.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions 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 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. 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. 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.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention.
7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record. All study intervention that is 
taken home by the participant, both used and unused, must be returned to the 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 38
investigator by the participant. Returned study intervention must not be redispensed 
to the participants.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
A qualified staff member will dispense the study intervention using the IRT system via 
unique container numbers in the bottles provided, in quantities appropriate according to the 
SoA. A second staff member will verify the dispensing. The participant or 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.
6.3. Measures to Minimize Bias: Randomization and Blinding
There will be no blinding measures, because the study is open label.
6.3.1. Allocation to Study Intervention
This is an open-label study and the specific study intervention dispensed to the participant 
will be assigned using an IRT. The site will contact the IRT prior to the start of study 
intervention administration for each participant. The site will record the study intervention 
assignment on the applicable CRF, if required. Potential bias will be reduced by the 
following steps: central randomization. Re-randomizations are not allowed. In case a 
participant is randomized in error, the participant must be discontinued from study before any 
study intervention is dispensed.
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be redispensed 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.
6.4. Study Intervention Compliance
Participant compliance with study intervention will be assessed at each visit by delegated site 
personnel. Compliance will be assessed by combination of counting returned tablets and 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 39
discussion with the participant during the site visits and documented in the source documents 
and CRF. Deviation(s) from the prescribed dosage regimen should be recorded in the CRF.
A record of the number of abrocitinib tablets dispensed to and taken by each participant must 
be maintained and reconciled with study intervention and compliance records. Intervention 
start and stop dates, including dates for intervention delays and/or dose reductions, will also 
be recorded in the CRF.
The following compliance cases will be considered medication errors and will be discussed 
with the sponsor for possible withdrawal from the study:

Participants administering >8 tablets in 1 day or administering ≥4 tablets/day for 
4 consecutive days;

Participants who have an overall compliance of 80% or 120% between visits for 
oral study intervention; 
Any deviation from protocol specified dosing should be recorded as a protocol deviation and 
the investigator or designee is to counsel the participant and parent(s)/legal guardian (if 
applicable) and ensure steps are taken to improve compliance. In addition, if the compliance 
deviation reaches the thresholds defined above it should also be recorded as a medication 
error (see Section 8.3.10).
6.5. Dose Modification
Dose modification is not allowed in this study. 
6.6. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation. 
Investigator may consider alternative forms of therapy for their participant until abrocitinib is 
potentially available.
6.7. Treatment of Overdose
For this study, any dose of study intervention greater than 8 tablets within a 24-hour time 
period (±2 hours) will be considered an overdose. 
There is no specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of study intervention 
(whichever is longer). Closely monitor the participant for any AEs/SAEs.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 40
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. A plasma sample for PK analysis may be requested by the Pfizer clinician 
(determined on a case-by-case basis).
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.
6.8. 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 will abstain from all prohibited concomitant medications as described in 
Section 6.8.2 and Appendix 7. Medications that are taken in the Screening 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 
will be documented as concomitant medications. All concomitant medications taken during 
the study must be recorded in study records with indication (if AD), reference to any 
associated adverse event, dose, and start and stop dates of administration. Participants will be 
queried about concomitant medication (including topical medications and treatments, 
over-the-counter and prescription medications and treatments, and vaccinations) at each 
study visit. Any new concomitant medications or dose changes to current concomitant 
medications should prompt evaluation 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.
The concomitant medication for any reason must be a locallyapproved medication and dose. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 41
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.
6.8.1. Permitted Concomitant Treatments
The following concomitant AD therapies are permitted during the study:

Oral antihistamines;

Non-medicated emollients and all topical medications for AD at the discretion of the 
investigator and in accordance with their usual practice.
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;

Hormonal contraceptives that meet the requirements of this study are allowed to be 
used in participants who are WOCBP (Refer to Appendix 4);

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).
6.8.2. 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 7). 
Participants should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications.
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.
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 medical monitor, the investigator will make a judgement on 
the ongoing eligibility of any participant with prohibited medication use during the study.
6.8.3. Rescue Medicine
After Week 4 if medically necessary, participants with intolerable AD symptoms may 
receive locally-approved rescue therapy with systemic corticosteroids for up to 14 days at a 
time, at the investigator’s discretion, according to local product label. Participants receiving 
systemic rescue therapy may continue to receive abrocitinib concurrently and should 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 42
continue study visits and assessments. Rescue therapy will be obtained locally and 
administration must be recorded on the CRF. As possible, investigators should conduct safety 
and efficacy assessments (eg, safety labs, disease severity scores) before administering 
rescue therapy. An unscheduled visit may be used for this purpose, if necessary. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following:

Other AE, per judgment of the investigator, requiring discontinuation from treatment 
(or, if necessary/desired, following discussion with sponsor).

Pregnancy.

Serious infection must result in temporary interruption of study intervention. Study 
intervention cannot be restarted until the serious infection has resolved and restarting 
study intervention has been 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 to restart 
study intervention, then the participant must be permanently discontinued from study 
intervention.

Any bleeding event thought to be associated with a platelet count reduction per the 
judgement of the investigator (or, if necessary/desired, following discussion with 
sponsor).

Any AE or laboratory abnormality, that per the investigator’s judgement requires 
temporary interruption to dosing of study intervention for 28 days.

Any AE of venous thromboembolism.

Participants who have recurrent SIB during the trial must be discontinued from the 
study and treated appropriately. If a participant endorses a 4 or 5 on the ideation 
subscale or any behavioral item of the C-SSRS on 2 occasions and is confirmed to 
have active SIB on both occasions by a risk assessment conducted by a qualified 
MHP, then the participant must be discontinued from the study and treated 
appropriately.

Estimated Creatinine Clearance 60 mL/min using the Cockcroft-Gault method.
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for end of treatment and end of study/follow-up assessments. See the SoA for 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 43
data to be collected at the time of discontinuation of study intervention and follow-up for any 
further evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
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. 
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 5 or if the 
investigator believes that it is in best interest of the participant.
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.
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

Behavioral, compliance or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 44
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to followup, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 45
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether 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 within 28 days prior to administration of the study intervention
to confirm that they meet the study population criteria for the study. If the time between 
Screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria and should be discussed and agreed with 
the Pfizer medical monitor.
Immediate safety concerns should be discussed with the sponsor as soon as possible upon 
awareness to determine if the participant should continue or discontinue study intervention.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The estimated total blood sampling volume for a participant who is in the study intervention 
phase for up to 12 weeks and who completes the EOT and Follow-up/EOS visits is 
approximately 50 mL. The actual collection times of blood sampling may change. Additional 
blood samples may be taken for safety assessments, and the investigator should remain 
mindful that the total blood volume taken during the study does not exceed limits established 
locally.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 46
8.1. Efficacy Assessments
8.1.1. Rater Qualifications
Clinical evaluations of AD will be performed by an experienced and qualified dermatologist 
(board certified or equivalent). An experienced and qualified non-dermatologist physician or 
experienced medical professional with experience in the conduct of dermatology clinical 
trials may be permitted to perform the clinical evaluations of AD when designated by the 
primary site investigator. The evaluator must receive and document protocol specific and 
applicable efficacy assessment scales training prior to performing these evaluations. To 
assure consistency and reduce variability, the same evaluator must assess all 
dermatological clinical evaluations for any individual participant throughout the study 
whenever possible; a back-up experienced and qualified, protocol-trained evaluator will 
only be allowed and documented in case of emergency or special situations when the 
designated evaluator is unable to perform the evaluation.
8.1.2. IGA
The Investigator’s Global Assessment of AD is scored on a 5-point scale (0-4), reflecting a 
global consideration of the erythema, induration and scaling. The clinical evaluator of AD 
will perform an assessment of the overall severity of atopic dermatitis and assign an IGA 
score and category as described in Table 1. The assessment will be a static evaluation without 
regard to the score at a previous visit. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 47
Table 1.
IGA Scores
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.
8.1.3. EASI
The EASI quantifies the severity of a participant’s AD based on both severity of lesion 
clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD 
clinical evaluator of the degree of erythema, induration/papulation, excoriation, and 
lichenification (each scored separately) for each of four body regions, with adjustment for the 
percent of BSA involved for each body region and for the proportion of the body region to 
the whole body. 
Lesion Severity by Clinical Signs: The basic characteristics of AD lesions - erythema, 
induration/papulation, excoriation, and lichenification -provide a means for assessing the 
severity of lesions. Assessment of these four main clinical signs is performed separately for 
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 2.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 49
Table 4.
EASI Area Score Criteria
Percent BSA with Atopic Dermatitis in a Body 
Region
Area Score
0%
0
>0 - <10%
1
10 - <30%
2
30 - <50%
3
50 - <70%
4
70 - <90%
5
90 - 100%
6
Body Region Weighting: Each body region is weighted according to its approximate 
percentage of the whole body (Table 5).
Table 5.
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 
four body regions resulting in an EASI score as described in Equation 3.
Equation 3: EASI = 0.1Ah(Eh+Ih+Exh+Lh) + 0.2Au(Eu+Iu+ExU+Lu) + 
0.3At(Et+It+Ext+Lt) + 0.4Al(El+Il+Exl+Ll)
A = Area Score; E = erythema; I = induration/papulation; Ex = excoriation; 
L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs
The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores 
representing greater severity of AD.
The EASI Clinical Sign Severity Scores for each of the 4 body regions and the involvement 
by total number of handprints for each of the 4 body regions will be recorded on the CRF.
8.1.3.1. BSA Efficacy
BSA Efficacy will be derived from the sum of the BSA affected by AD as measured in 
handprints across the 4 body regions assessed as part of the EASI assessment (refer to 
Table 4). Handprint refers to that of each individual participant for their own measurement. 
The BSA Efficacy ranges from 0 to 100%, with higher values representing greater body 
surface area affected with AD. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 50
8.1.4. 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). 
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).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 51
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). 
SCORAD Total Score
The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range 
from 0 to 103).
8.1.5. PROs
The PROs included in this study have all been recommended by the HOME initiative as core 
outcomes to be measured in eczema trials. 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. 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.
8.1.5.1. PP-NRS
The severity of itch (pruritus) due to AD will be assessed using the PP-NRS, a validated 
horizontal NRS.11,12 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 at the Screening Visit to determine 
eligibility criteria (See Section 5.1). 
8.1.5.2. POEM
The POEM is a validated 7-item PRO measure used to assess the impact of AD recalled over 
the past week. This instrument is appropriate for use by participants aged 12 years and 
older.13-15
8.1.5.3. ADCT
The ADCT is a brief patient self-administered instrument designed and validated to assess 
patient-perceived AD control; 6 AD symptoms and impacts are evaluated over the past week, 
including overall severity of symptoms, days with intense episodes of itching, intensity of 
bother, problem with sleep, impact on daily activities, and impact on mood or emotions.16,17

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 52
8.1.6. Photography
Photographs of representative AD lesions should be obtained at Baseline/Day 1, EOT and 
EOS/follow-up visit.  Areas photographed should be recorded in source documents so that 
the same AD body region(s) will be photographed at each time point. Photographs will be 
utilized for illustrative purposes and not formally evaluated as an endpoint for analysis.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, assessments of the head, ears, 
eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, 
musculoskeletal, and neurological systems.
A brief physical examination will include, at a minimum, assessments of the general 
appearance, the respiratory and cardiovascular systems, and participant reported symptoms.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to 8.3.3.
8.2.2. Vital Signs
Vital sign measurements including oral temperature, pulse rate and blood pressure will be 
assessed (pre-dose, if applicable). Blood pressure and pulse rate will be collected on the 
CRF. Temperature will not be collected on the CRF.
Blood pressure and pulse rate measurements will be assessed with the participant in a seated 
position with a completely automated device. Manual techniques will be used only if an 
automated device is not available.
Blood pressure and pulse rate measurements should be preceded by at least 5 minutes of rest 
for the participant in a quiet setting without distractions (eg, television, cell phones). 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 53
Participants should refrain from smoking or ingesting caffeine during the 30 minutes 
preceding the measurements.
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. Chest X-rays may 
also be completed at the investigator’s discretion to aid in TB status determination of 
participants requiring TB testing. Completion of the chest X-ray (or other appropriate 
diagnostic image) will be recorded on the CRF, and results and documentation will need to 
be available from the participant’s medical record upon request by the sponsor.
8.2.4. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) 
should not be used given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement. All scheduled ECGs should be performed after the participant 
has rested quietly for at least 5 minutes in a supine position. 
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is 450 msec; or b) 
an absolute QT value is ≥500 msec for any scheduled ECG for greater than 4 hours (or 
sooner, at the discretion of the investigator); or c) QTcF intervals get progressively longer, 
the participant should undergo continuous ECG monitoring. A cardiologist should be 
consulted if QTcF intervals do not return to less than the criteria 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 QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 6.
8.2.5. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA
and the Substudy SoA for the timing and frequency. All protocol-required laboratory 
assessments, as defined in Appendix 2, must be conducted in accordance with the laboratory 
manual, the SoA, and the Substudy SoA. Unscheduled clinical laboratory measurements may 
be obtained at any time during the study to assess any perceived safety issues.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 54
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.
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
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.
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.6. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA. 
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the study intervention. Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study. Pregnancy tests may also be 
repeated if requested by IRBs/ECs or if required by local regulations. If a urine test cannot be 
confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such 
cases, the participant must be excluded if the serum pregnancy result is positive.
8.2.7. Knee MRI
See Appendix 10 for details of the knee MRI substudy.
8.2.8. Suicidal Ideation and Behavior Risk Monitoring
The C-SSRS is a validated tool for investigative staff to use to evaluate suicidal ideation and 
behavior.18
Trained site staff are to administer the C-SSRS to all participants at study visits and score 
immediately. Based on the judgment of the investigator, the participant should either be 
permitted to continue in the study or must have a risk assessment done by a qualified medical 
health professional to assess whether it is safe to continue 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 since the last 
assessment: “Yes” answers on items 4 or 5 of the C-SSRS.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 55

Previous history of suicidal behavior since the last assessment: “Yes” answer to any 
of the suicidal behavior items of the C-SSRS.

Any lifetime history of serious or recurrent suicidal behavior (non-suicidal 
self-injurious behavior is not a trigger for a risk assessment unless it is indicated 
according to the investigator’s judgement).
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.3.1, each participant/parent/legal 
guardian/legally authorized representative will be questioned about the occurrence of AEs in 
a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days, except as indicated below, after the last administration of the 
study intervention. 
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.
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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 56
If a participant permanently 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 information on 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 Nonserious 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.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-Up of AEs and SAEs
After the initial AE or 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. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 57
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 toward 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, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure, occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention up to 28 days after last dose of 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 EDP:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 58
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 
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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 59
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if:

A female participant is found to be breastfeeding while receiving or up to 28 days 
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 ingestion. 
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 24 
hours of the investigator’s awareness using the CT SAE Report Form, regardless of whether 
there is an associated SAE. Since the information about the occupational exposure 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 must be 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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 60
8.3.8.1. Lack of Efficacy
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to Pfizer 
Safety only if associated with an SAE. 
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Other examples include, but are not limited to:

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;

The administration of study intervention that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 61
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.5. Genetics
8.5.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.6. Biomarkers
Biomarkers are not evaluated in this study.
8.7. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
Data analysis and statistical methods for the MRI substudy in adolescents are described in 
Section 10.10.
9.1. Statistical Hypotheses
9.1.1. Estimands
9.1.1.1. Primary Estimand
The primary estimand is defined by the following attributes:
Population: Patients aged 12 years and older with moderate to severe AD.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 62
Variable: Binary indicator of whether any AE/SAE occurred at least once.
Treatment condition: The randomized intervention regardless of intercurrent events.
The intercurrent events “intervention discontinuation for any reason” and “intervention 
compliance” are both addressed by the treatment condition of interest. 
Population-level summary: Incidence rate of AEs/SAEs, defined as the number of 
participants with AEs/SAEs from the time of first dose to Week 16 divided by the number of 
participants, in each treatment arm.
9.1.1.2. Secondary Estimands
The secondary estimand 1 is defined by the following attributes:
Population: Patients aged 12 years and older with moderate to severe AD. 
Variable: Response based on IGA score of clear (0) or almost clear (1) and greater than or 
equal to 2 points improvement from baseline at Week 12; participants who discontinued 
intervention for any reason are considered as non-responders.
Treatment condition: The randomized intervention. 
The intercurrent event “intervention discontinuation for any reason” is addressed in the 
variable definition.
Population-level summary: IGA response rate with 95% CI, in each treatment arm.
The secondary estimand 2 is defined by the following attributes:
Population: Patients aged 12 years and older with moderate to severe AD. 
Variable: Response based on improvement of ≥75% from baseline EASI score at Week 12; 
participants who discontinued intervention for any reason are considered as non-responders.
Treatment condition: The randomized intervention. 
The intercurrent event “intervention discontinuation for any reason” is addressed in the 
variable definition.
Population-level summary: EASI-75 response rate with 95% CI, in each treatment arm.
The secondary estimand 3 is defined by the following attributes:
Population: Patients aged 12 years and older with moderate to severe AD. 
Variable: Response based on improvement of ≥75% in SCORAD from baseline at Week 12; 
participants who discontinued intervention for any reason are considered as non-responders.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 63
Treatment condition: The randomized intervention. 
The intercurrent event “intervention discontinuation for any reason” is addressed in the 
variable definition.
Population-level summary: SCORAD75 response rate with 95% CI, in each treatment arm.
The secondary estimand 4, is defined by the following attributes: 
Population: Patients aged 12 years and older with moderate to severe AD.
Variable: Change from baseline in POEM at Week 12 and at all scheduled timepoints; data 
after treatment discontinuation at any time during the treatment period will be censored. 
Treatment condition: The randomized intervention.  The intercurrent event “intervention 
discontinuation for any reason” is addressed in the variable definition.
Population-level summary: Mean and standard deviation. 
The secondary estimand 5 is defined by the following attributes: 
Population: Patients aged 12 years and older with moderate to severe AD.
Variable: Change from baseline in ADCT at Week 12 and at all scheduled timepoints; data 
after treatment discontinuation at any time during the treatment period will be censored. 
Treatment condition: The randomized intervention.
The intercurrent event “intervention discontinuation for any reason” is addressed in the 
variable definition.
Population-level summary: Mean and standard deviation. 
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Enrolled
All participants who sign the ICD.
Full analysis set 
All participants randomly assigned to study intervention 
and who take at least 1 dose of study intervention.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 64
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.3.1. General Considerations
Study data will be summarized and presented separately for the following treatment arms:

abrocitinib 100 mg QD

abrocitinib 200 mg QD.
9.3.2. Primary Endpoint Analysis
Analysis of the incidence of AEs and SAEs will be performed on the FAS. Participants will 
be analyzed according to the treatment they actually received. The number and percentage of 
treatment-emergent AEs will be summarized according to type, frequency, severity, 
seriousness and relationship to abrocitinib in each treatment arm. In addition, withdrawals 
from active treatment due to AEs and serious infections, defined as any infection (viral, 
bacterial, and fungal) requiring hospitalization or parenteral antimicrobials or meets other 
criteria that require it to be classified as a serious adverse event, will be summarized 
descriptively.
9.3.3. Secondary Endpoint Analysis
Analysis of secondary endpoints will be performed on the FAS. Participants will be analyzed 
according to the treatment arm they are randomized to. The IGA, EASI-75 and SCORAD75 
response rates, together with the corresponding 95% CI (using the normal approximation or 
Clopper-Pearson exact method, whichever is appropriate) will be estimated for each 
treatment arm. Descriptive statistics for change from baseline in POEM and ADCT scores 
will be derived at all scheduled timepoints, for each treatment arm.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is an open-label study, 
the sponsor may conduct reviews of the data, including MRI data, during the course of the 
study for the purpose of safety assessment or to support regulatory submissions. Interim 
safety and efficacy data after approximately 50% of the total sample size has been 
randomized in the study will be prepared and summarized to support presentation of initial 
results to India BoH.
9.5. Sample Size Determination
A sufficient number of participants will be screened to achieve 200 participants randomly 
assigned to study intervention. The sample size of 100 randomized participants per treatment 
arm would allow estimation of the incidence rate of any AE with maximum margin of error 
of 10%, in each treatment arm.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 65
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:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents (eg, 
advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC by 
the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 66
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 the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and sub investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate 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, including the 
risks and benefits, to the participant or his/her legally authorized representative and answer 
all questions regarding the study. The participant or his/her legally authorized representative
should be given sufficient time and opportunity to ask questions and to decide whether or not 
to participate in the trial.
Participants must be informed that their participation is voluntary. Participants 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, privacy and data 
protection requirements, where applicable, and the IRB/EC 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 or his or her legally authorized representative 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 or his or her 
legally authorized representative.
The participant or his or her legally authorized representative 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/EC 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 on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 67
Participants or his or her legally authorized representative must be reconsented to the most 
current version of the ICD(s) during their participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.
For pediatric participants: 
The investigator or his/her representative will explain the nature of the study to the 
participant and his/her parent(s)/legal guardian and answer all questions regarding the 
study. The participant and his/her parent(s)/legal guardian should be given sufficient time 
and opportunity to ask questions and to decide whether or not to participate in the trial.
When consent is obtained from a participant’s parent(s)/legal guardian, the participant’s 
assent (affirmative agreement) must be subsequently obtained when the participant has the 
capacity to provide assent, as determined by the IRB/EC. If the investigator determines that 
a participant’s decisional capacity is so limited he/she cannot reasonably be consulted, 
then, as permitted by the IRB/EC and consistent with local regulatory and legal requirements, 
the participant’s assent may be waived with source documentation of the reason assent was 
not obtained. If the study participant does not provide his or her own assent, the source 
documents must record why the participant did not provide assent (for example, minor child), 
how the investigator determined that the person signing the consent was the 
participant’s parent(s)/legal guardian, the consent signer’s relationship to the study 
participant, and that the participant’s assent was obtained or waived. If assent is obtained 
verbally, it must be documented in the source documents.
If study participants are minors who reach the age of majority during the study, as recognized 
under local law, they must be reconsented as adults to remain in the study. If the enrollment 
of emancipated minors is permitted by the IRB/EC and local law, they must provide 
documentation of legal status to give consent without the permission of a legally authorized 
representative.
Participants and their parent(s)/legal guardian must be informed that their participation is 
voluntary. Participant’s parent(s)/legal guardian will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, HIPAA requirements, where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant’s parent(s)/legal guardian and the 
study participant as applicable 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’s parent(s)/legal guardian must be informed that the participant’s 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’s parent(s)/legal 
guardian.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 68
The participant’s parent(s)/legal guardian must be informed that the participant’s medical 
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
The investigator further must ensure that each study participant’s parent(s)/legal guardian is 
fully informed about his or her right to access and correct his or her child’s personal data and 
to withdraw consent for the processing of his or her child’s personal data keeping in mind the 
privacy rights that may restrict access of older adolescents medical records by their 
parent(s)/legal guardian in certain regions.
The source documentation must include a statement that written informed consent and as 
applicable, assent, was obtained before the participant was enrolled in the study and the date 
the written consent/assent was obtained. The authorized person obtaining the informed 
consent must also sign the ICD.
Parent(s)/legal guardian and the participant must be reconsented to the most current version 
of the ICD(s)/assent during their participation in the study.
A copy of the ICD(s) and assent, if written, must be provided to the parent(s)/legal 
guardian and the participant.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will 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 participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets 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 and medical record ID. 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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 69
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will not use a DMC.
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 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 SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the 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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 70
Data sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the clinical study 
report.
The investigator must permit study-related monitoring, audits, IRB/EC 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, including definition of study critical data items and 
processes (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, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 71
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as 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 the sponsor or its agents immediately of any regulatory retain 
notification in relation to the study. Furthermore, the investigator will cooperate with the 
sponsor or its agents to prepare the investigator site for the inspection and will allow the 
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 the sponsor or its agent. Before response submission to 
the regulatory authorities, the investigator will provide the 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 site.
Data reported on the CRF or entered in the eCRF that are 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.
In this study, the CRF will serve as the source document. A document must be available at 
the investigative site that identifies those data that will be recorded on the CRF and for which 
the CRF will be the source document.
Definition of what constitutes source data and its origin can be found in the Clinical 
Monitoring Plan, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 72
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor if 
requested to do so by the responsible IRB/EC 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/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator; 

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.10. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the 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 submits all manuscripts or abstracts to the sponsor 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 73
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 for 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 for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 74
10.2. Appendix 2: Clinical Laboratory Tests
The laboratory tests detailed in Table 6 will be performed at times defined in the SoA section 
and the Substudy SoA section of this protocol and analyzed at local laboratories. Laboratory 
tests with abnormal results may be repeated once during the screening period; the last value 
will be used to determine eligibility. Additional laboratory results may be reported on these 
samples as a result of the method of analysis or the type of analyzer used by the clinical 
laboratory, or as derived from calculated values. These additional tests would not require 
additional collection of blood. Unscheduled clinical laboratory measurements may be 
obtained at any time during the study to assess any perceived safety issues. 
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. 
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:

Refer to Section 5.1 Inclusion Criteria and Section 8.2.6 Pregnancy Testing for 
screening pregnancy criteria.

For details of timing of recommended pregnancy testing refer to the SoA.
Table 6.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Lipid Profilea
Other
Hemoglobin
WBC count
Neutrophils (%, Abs)
Lymphocytes (%, Abs)
Platelets
Coagulation Panel 
(APTT, PT/INR)
Urea
sCr
sCysC (at Screening)
Estimated Creatinine 
Clearance
AST
ALT
TBili
Alkaline phosphatase
Total cholesterol
LDL
VLDL
HDL
Triglycerides
At Screening only:

FSHb

Serum pregnancy test 
(β-hCG, for WOCBP 
only)c

HBsAg

HIV

HCV

TB test (as per site 
standards)
a.
Fasting lipid profile panel requires at least an 8-hour fast. If possible, participants should comply with 
fasting requirements at those visits per the SoA and the Substudy SoA.
b.
For confirmation of postmenopausal status only.
c.
Urine pregnancy test (for WOCBP only) will be performed at all visits other than screening visits.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 78
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
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, 
All AEs or SAEs associated 
with exposure during 
pregnancy or breastfeeding
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF.
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated SAE). 
**
Environmental or 
occupational exposure to 
the product under study to 
a non-participant (not 
involving EDP or EDB).
None. Exposure to a study 
non-participant is not 
collected on the CRF.
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.***
*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using CT SAE Report Form and EDP Supplemental Form; if the EDP is associated with an SAE, 
then the SAE is reported to Pfizer Safety using the CT SAE Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form which would also include details 
of any SAE that might be associated with the EDB. 
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 

When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE or SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or 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 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 83
10.4. Appendix 4: Contraceptive and Barrier 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 the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenarchal.
2. Premenopausal female with 1 of the following: 

Documented hysterectomy;

Documented bilateral salpingectomy;

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 84

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above 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.
3. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

A 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 (eg, bilateral tubal ligation).
5. Vasectomized partner:

A 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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 85
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;
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).

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 86
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede 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 
laboratory 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:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 87
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/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/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or 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, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 91
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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 92
10.8. Appendix 8: 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 in India 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). 
10.8.1. 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 (eg, audio, video, 
video-conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit:

Review and record abrocitinib dosing information, including compliance and missed 
doses.

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 93
10.8.2. Alternative Facilities for Safety Assessments
10.8.2.1. Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local 
regulations. The local laboratory may be a standalone institution or within a hospital. The 
following safety laboratory evaluations may be performed at a local laboratory: 
Hematology
Chemistry
Lipid Profilea
Other
Hemoglobin
WBC count
Neutrophils (%, Abs)
Lymphocytes (%, Abs)
Platelets
Coagulation Panel 
(APTT, PT/INR)
Urea
sCr
sCysC (at Screening)
Estimated Creatinine 
Clearance
AST
ALT
TBili
Alkaline phosphatase
Total Cholesterol
LDL
VLDL
HDL
Triglycerides
At Screening only:

FSHb

Serum pregnancy test 
(β-hCG, for WOCBP 
only)c

HBsAg

HIV

HCV

TB test (as per site 
standards)
a.
Fasting lipid profile panel requires at least an 8-hour fast. If possible, participants should comply 
with fasting requirements at those visits per the SoA.
b.
For confirmation of postmenopausal status only.
c.
Urine pregnancy test (for WOCBP only) will be performed at all visits other than screening.
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 mIU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol.
10.8.2.2. 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.
10.8.3. Study Intervention
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 94
Abrocitinib 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 abrocitinib by mail. The tracking record 
of shipments and the chain of custody of abrocitinib 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 third-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.
10.8.4. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided. Temporary discontinuation of the study 
intervention may be medically appropriate until the participant has recovered from 
COVID-19, if the investigator judges this as required, with or without discussion with the 
sponsor as required.
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 95
10.9. Appendix 9: Abbreviations
This following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
Abs
absolute
AD
atopic dermatitis
ADCT
Atopic Dermatitis Control Tool 
AE
adverse event
ALT
alanine aminotransferase
APTT
activated partial thromboplastin time
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the curve
AV
atrioventricular
-hCG
beta-human chorionic gonadotropin
BoH
Board of Health
bpm
beats per minute
BSA
body surface area
CD
cluster of differentiation
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CsA
cyclosporine A
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
CYP
cytochrome P450
DDI
drug-drug interaction 
DILI
drug-induced liver injury
DMC
data monitoring committee
EASI
Eczema Area and Severity Index
EBV
Epstein Barr virus
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
EMA
European Medicines Agency

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 96
Abbreviation
Term
EOS
end of study
EOT
end of treatment
EU
European Union
EudraCT
European Clinical Trials Database
FACS
fluorescence activated cell sorting
FAS
full analysis set
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma glutamyl transferase
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDL
high-density lipoprotein
HIPAA
Health Insurance Portability and Accountability Act
HOME
Harmonising Outcome Measures for Eczema
HSS Pedi-FABS
Hospital for Special Surgery Pediatric Functional Activity Brief 
Scale
HT SDS
height standard deviation scores
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICD
informed consent document
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IFN
interferon
IGA
Investigator’s Global Assessment
IL
interleukin
IMP
investigational medicinal product
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IP manual
investigational product manual
IR
incidence rate
IRB
Institutional Review Board
IRC
internal review committee
IRT
interactive response technology
JAK
Janus kinase
LDL
low-density lipoprotein
LFT
liver function test
MHP
medical health professional
MRI
magnetic resonance imaging
N/A
Not Applicable
NOAEL
no observed adverse effect level
NOEL
no observed effect level

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 97
Abbreviation
Term
PK
pharmacokinetic(s)
POC
proof of concept
POEM
Patient-Oriented Eczema Measure
PP-NRS
Peak Pruritus Numerical Rating Scale
PR
pulse rate
PRO
patient reported outcome
PSAAD
Pruritus and Symptoms Assessment for Atopic Dermatitis
PT
prothrombin time
PVC
premature ventricular contraction
PY
patient year
QD
once daily
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
QTL
quality tolerance limit
SAE
serious adverse event
SAP
Statistical Analysis Plan
SCORAD
SCORing Atopic Dermatitis
sCr
serum creatinine
sCysC
serum Cystatin C
SDS
standard deviation scores
SIB
suicidal ideation and behavior
SoA
schedule of activities
SOC
System Organ Class
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBili
total bilirubin
TSLP
thymic stromal lymphopoietin
TYK
tyrosine kinase
ULN
upper limit of normal
US
United States
VAS
visual analog scale
VLDL
very-low-density lipoprotein
VTE
venous thromboembolism
WBC
white blood cell
WOCBP
woman/women of childbearing potential

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 98
10.10. Appendix 10: An Imaging Substudy for Evaluation of Abrocitinib’s Potential 
Effects on Adolescent Bone in Participants With Moderate to Severe AD in India
10.10.1. Substudy Introduction
10.10.1.1. Substudy Background and Rationale
JAK signaling plays an important role in bone development and metabolism. Data from 
abrocitinib and other JAK inhibitors such as baricitinib and upadacitinib indicate clear JAK 
class-related bone effects after in utero exposure.19,20 However, the direct effects of JAK 
inhibitors on bone development remain unclear. Importantly, atopic dermatitis is associated
with systemic corticosteroid use which can lead to poor bone health. AD patients may have 
decreased bone health including a higher fracture rate relative to controls.21 Currently 
approved JAK inhibitors show differences in selectivity for individual JAK enzymes and 
cytokine signaling pathways, and at present there is incomplete understanding of their 
specific contribution to potential effects regarding bone development, or lack thereof.
Nonclinical bone microscopic finding of decreased primary spongiosa in the metaphysis 
bone (femur/tibia) region was noted in young rat (comparable human age of ≥12 years) short 
duration (up to 1 month) repeat-dose toxicity studies. This microscopic long bones finding 
was transient, nonprogressive and the NOEL exposure margin at which no bone finding was 
noted was at least 6x the unbound human AUC at the maximum clinical dose of 200 mg QD
(the bone finding was noted at ≥23×). No abrocitinib related clinical observations, 
macroscopic, or microscopic, by histopathological examination, long bones findings were 
observed in rats at any dose in the 6-month toxicity study (up to 26x the unbound human 
AUC at the maximum clinical dose of 200 mg QD) or in young or adult monkeys in any of 
the toxicity studies up to 9 months in duration (up to 31 × the unbound human AUC at the 
maximum clinical dose of 200 mg QD). Young monkeys (comparable human age of 8 years 
and older) are a sensitive nonclinical species for the detection of potential effects on bone 
growth and development relevant to adolescent humans because: (1) young monkeys have 
less active growth plates compared to rats of similar age, and (2) the physiologic ambulatory 
activity and bone biomechanical loading are similar between young monkeys and human 
adolescents. Therefore, it is unlikely that the observations in the repeat-dose rat toxicity 
studies have a clinically significant consequence for adolescent humans. In a juvenile rat 
toxicity study to support using abrocitinib in children <12 years of age, bone findings 
(decreased femur bone length and width, bone malrotations, macroscopic femoral head and 
neck abnormalities including occasional long bone fractures) occurred in a time period when 
femoral bone neck development was still on-going in early postnatal development in these 
juvenile rats (postnatal day 10; comparable to approximately 3-months human age at dose 
initiation).22
Height SDS and fracture rates have been previously assessed in adolescent participants in 
order to assess whether the microscopic, transient nonclinical finding in rats translated to 
changes in adolescent bone growth and development. HT SDS is the standard for measuring 
changes in height in clinical trials as it allows efficient use of data across both ages and 
genders.23 In the safety update data, including B7451036, at each dose and time point where 
the HT SDS was assessed the median change was 0, suggesting that participants remain on 
the growth curve that had been established prior to abrocitinib dosing. Fracture rates is a 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 99
relevant measure for assessment of a clinically meaningful impact on bone. Fracture rates are 
high in adolescence because there is a lag in mineralization relative to bone 
lengthening.24 The fracture rates in adolescent participants in the safety update data, 
including B7451036, representing an IR of 0.92/100 (CI, 0.25, 2.35) patient years. To 
contextualize the rate of fractures in the abrocitinib development program, the IR of fracture 
in a large Danish Health Registry (3,909 patients with AD aged 12 to <18) was 2.72/ 100 PY 
(272.19/10,000 PY) [Danish Report Table 15].
This substudy will provide imaging data to further evaluate whether abrocitinib has any 
potential effects on adolescent bone with regard to bone safety findings in knee MRI, 
including to assess if there is any abrocitinib-associated effects on cartilage mineralization in 
the actively growing bones of adolescent participants with moderate to severe AD and to 
verify that epiphyseal plate closure occurs as expected in late adolescence or early adulthood. 
Findings of the substudy will further inform risk assessment as to whether administration of 
abrocitinib may affect bone in adolescents. 
Knee MRI is the selected imaging modality and body site utilized in the substudy for several 
reasons:

The spatial resolution for MRI provides the best opportunity to identify morphologic 
changes that may be related to abrocitinib exposure. 

MRI permits visualization of the ossification centers and verification of epiphyseal 
plate closure. 

MRI does not require ionizing radiation exposure for adolescent participants. 
The knee is a suitable body site to evaluate because there are 3 ossification centers.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 102
10.10.3. Substudy Objectives and Endpoints
Primary substudy objective(s):
Primary substudy endpoint (as secondary endpoints for 
B7451094):

To evaluate the potential effects of abrocitinib on 
bone development in adolescent participants 12 to 
<18 years of age, as assessed by knee MRI.

The proportion of bone safety findings in knee MRI 1 
year after randomization in adolescent participants 
exposed to abrocitinib 100 mg and 200 mg QD.
10.10.4. Substudy Design
This is a substudy of the main B7451094 open label parallel group study. This substudy is 
being performed to evaluate whether abrocitinib has any potential effects on adolescent bone 
with regard to bone safety findings in knee MRI, including to assess if there is any 
abrocitinib associated effects on cartilage mineralization in the actively growing bones of 
adolescent participants with moderate to severe AD in India, and to verify that epiphyseal 
plate closure occurs as expected in late adolescence or early adulthood. All adolescent 
participants who were 12 to <18 years of age at the screening visit will be enrolled in this 
substudy. This substudy will continue until 1 year after all enrolled adolescent participants in 
the main study have been randomized to study intervention. 
Prior to knee MRI at the screening visit of the main study, informed consent and assent (if 
applicable) will be obtained. Adolescent participants will continue to receive the assigned 
abrocitinib 100 mg or 200 mg QD after the 12-week treatment period in the main study, until 
1 year after the participant was randomized in the main study, when a second MRI imaging 
will be performed at the substudy end of treatment visit. Both imaging sessions will require 
participants to be in a supine position in the confined space of the MRI scanner for 
approximately 30 minutes. 
The same knee for each participant will be evaluated in the substudy. The default knee 
selected to be evaluated will be the participant’s left knee. The right knee will only be 
selected and used if there is a prior history of significant trauma or abnormality of the left 
knee, such as any knee condition requiring surgery, any knee condition that is a birth defect, 
or any condition which has resulted in long-term (>6 months) knee pain, reduction in knee 
function, or abnormal gait (Note: This is not an all-inclusive list), or any other reason that the 
left knee is unsuitable for MRI in the Investigator's judgement. 
MRIs will be evaluated by a central reader, and reviewers will be radiologists; who are 
experienced in pediatric imaging and proficient in the interpretation of pediatric bone 
imaging. The assessments will include evaluation of epiphyseal plate closure and 
mineralization of cartilage at the growth centers. The radiologist(s) will evaluate the images 
using a standardized case report form. If any bone safety finding(s) are determined to be 
present in the central evaluation of the post-dose knee MRI images at the substudy end of 
treatment visit or early termination visit, then the adjudication committee will adjudicate the 
diagnosis as per the adjudication charter. The Investigator will determine based on the MRI 
central read and (if relevant) any suggested further assessment/investigation made by the 
adjudication committee, and (if relevant) the adjudication outcome if any further follow-up 
or investigation is required. The Investigator will be responsible for recording any medical 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 103
history or AEs that they determine. The Investigator holds responsibility for reviewing all 
MRI central read reports and adjudication outcomes, and performing a general safety review 
based on these. 
The participants of this substudy will complete all other protocol-specific procedures in the 
main study.  
Adolescent participants who discontinue from the main study will also be discontinued from 
the substudy. For participants that withdraw during the main study period, an end of 
treatment/early termination knee MRI for the participant should be performed approximately 
within 1 month of the main study end of treatment/early termination visit, and then the 
participant should enter into the follow-up period, with a main study end-of-study visit 
scheduled for 4 weeks after the end of treatment visit MRI. 
10.10.5. Substudy Eligibility Criteria
This substudy can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
substudy is considered appropriate. All relevant medical and nonmedical conditions should 
be taken into consideration when deciding whether a particular participant is suitable for this 
substudy. 
Participant eligibility should be reviewed and documented by an appropriate member of the 
Investigator’s study team before participants are included in the substudy. 
10.10.5.1. Substudy Inclusion Criteria
Participant must meet all of the following inclusion criteria to be eligible for enrollment into 
the substudy:
1. 12 to 18 years of age, at the time of screening visit;
2. Evidence of a personally signed and dated informed consent document, and/or 
informed consent of the legally authorized representative (parent/guardian), and 
assent of the study participant, indicating that the participant or their parent(s)/legal 
guardian, if applicable, have been informed of all pertinent aspects of the substudy;
3. At least one knee suitable for MRI in the Investigator’s judgment, without prior 
history of significant trauma or abnormality eg, any knee condition requiring surgery, 
any knee condition that is a birth defect, or any condition which has resulted in long-
term (6 months) knee pain, reduction in knee function, or abnormal gait (Note: This 
is not an all -inclusive list);
4. Willing and able to comply with substudy scheduled visits and subsstudy procedures 
including knee MRI imaging.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 104
10.10.5.2. Substudy Exclusion Criteria
Participant with any of the following characteristics/conditions will not be included in the 
study:
1. Participant who has any absolute or relative contraindication for an MRI scan, such as 
implants, metallic foreign bodies, claustrophobia. (Note: This is not an all inclusive 
list).
10.10.5.3. Substudy Enrollment Criteria
Participants will be enrolled into the substudy provided they have an appropriately signed 
informed consent document and have evidence of assent, if applicable (ie, current minors), to 
participate in the substudy, and meet all inclusion and none of the exclusion criteria for 
participation in the substudy at the screening/enrollment visit. 
10.10.5.4. Substudy Lifestyle Requirements
There are no additional requirements for the substudy. The requirements from the main 
protocol apply. Please refer to the Lifestyle Considerations section (Section 5.3) of the main 
protocol for further details. 
10.10.6. Substudy Study Treatments
There are no additional requirements for the substudy and the requirements from the main 
study apply, except that adolescent participants who enter the substudy will continue to 
receive study intervention as assigned in the main study after the 12-week treatment period, 
until 1 year after randomization in the main study or until they turn 18 years of age. 
Participants will be dispensed bottles of study intervention at Week 12, Week 24 and Week 
36 visits. Please refer to the Study Intervention(s) and Concomitant Therapy section 
(Section 6) of the main protocol for further details.
10.10.7. Substudy Study Procedures
The study procedures for the substudy are described below.
If for whatever unanticipated reason a participant is unable to attend the site visit, the 
substudy procedures may be performed remotely where locally permissible and where an 
acceptable and feasible approach has been agreed with the study team and/or detailed per 
protocol.
10.10.7.1. Substudy Screening/Enrollment and Initial Knee MRI Evaluation

Substudy details will be included in the main study informed consent, and/ or assent 
(if applicable). Informed consent or assent will be required prior to performing any 
procedure for the substudy. 

Assess knees of the participant for relevant history. 

Review substudy inclusion and exclusion criteria.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 105

Participants who meet the substudy eligibility and enrollment criteria may enroll in 
the substudy. Participants who do not meet these criteria must not enroll in the 
substudy and therefore cannot enroll in the main study. 

Participant substudy enrollment will be recorded in the substudy CRF. 

There will be no separate screening/enrollment visit for the substudy. An MRI should 
be arranged to occur pre-dosing, promptly following the main study 
screening/enrollment visit. After the initial MRI review if any abnormal knee MRI 
findings then:
o
Review findings identified by central reader MRI evaluation, and arrange any 
further follow-up and investigation, if relevant and required;
o
Record medical history/adverse event as appropriate. 

Monitor if any discontinuation criteria for the substudy have been met or not per the 
substudy Schedule of Activities (Section 10.10.2). The main study discontinuation 
criteria will also apply for substudy. 
10.10.7.2. Substudy Early Termination/End of Treatment Visit

A Substudy End/Early Termination Visit will be performed approximately within 1 
month of the participant turning 18 years of age, OR whenever the participant 
discontinues from the substudy, OR 1 year after participant randomization in the main 
study; whichever is the sooner.

An MRI should be arranged approximately within 1 month of the visit (but must be 
AFTER the participant has turned 18 years of age if participant is completing substudy 
due to turning 18).

After the MRI is performed, review if any abnormal knee MRI findings then: 
o
Review findings identified by central reader MRI evaluation, and (if relevant) the 
adjudication report, and arrange any further follow-up and investigation, if 
relevant and required;
o
Record medical history/adverse event/laboratory assessment abnormality as 
appropriate. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 106
10.10.7.3. Substudy Follow-up Visit

MRI may be required if any clinically significant finding is identified in knee MRI 
following the substudy early termination/end of treatment visit or if for any reason 
MRI was not performed following the end of treatment visit. This MRI, if required, 
must be performed prior to the substudy follow up visit. After the MRI is performed, 
review if any abnormal knee MRI findings then:
o
Review findings identified by central reader MRI evaluation, and (if relevant) the 
adjudication report, and arrange any further follow-up and investigation, if 
relevant and required;
o
Record medical history/adverse event as appropriate.
Note: if any participant requires MRI following the end of treatment visit, the expectation is 
that the MRI would be arranged as soon as feasible and that the substudy follow up visit be 
conducted as close to the stated visit window as possible. It will not be considered a protocol 
deviation as long as the substudy follow up visit occurs no more than 14 days after the 
completion of the MRI in such cases.
10.10.7.4. Substudy Discontinuation Criteria
A participant will be discontinued from the substudy and have a Substudy Early 
Termination/End of Treatment Visit if:

The participant meets any of the discontinuation criteria of the main B7451094 study;

If the participant is no longer an active participant of the main B7451094 study;

If the participant has turned 18 years of age during the substudy.
10.10.7.5. Substudy Participant Withdrawal
Participants may withdraw from the substudy at any time and for any reason. Participants 
will be withdrawn from the substudy if they are no longer an active participant of the main 
study. The requirements and discontinuation criteria from the main protocol apply for the 
substudy. Please refer to Participant Withdrawal section (Section 7.2) of the main protocol 
for further details.
10.10.8. Substudy Assessments
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the Investigator that may make it unfeasible to 
perform the test. In these cases, the Investigator will take all steps necessary to ensure the 
safety and well-being of the participant. When a protocol-required test cannot be performed, 
the Investigator will document the reason for this and any corrective and preventive actions 
that he or she has taken to ensure that normal processes are adhered to as soon as possible. 
The study team will be informed of these incidents in a timely manner. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 107
10.10.8.1. Bone Safety Findings Identified in Central Evaluation of Knee MRI Images
All bone safety findings will be recorded in the CRF as either medical history or treatment 
emergent adverse events, as determined by the Investigator.
If any bone safety finding(s) are determined to be present in the central evaluation of the 
postdose knee MRI images, then the adjudication committee will adjudicate the diagnosis as 
per the adjudication charter.. The adjudication committee may suggest further follow up or 
investigation for Investigator consideration. The Investigator will receive a report of the MRI 
central read and the adjudication outcome, and will determine if any further follow-up or 
investigation is required. 
The Investigator will ensure the recording of any AEs as described in the Adverse Event 
Reporting section (Section 8.3 and Section 10.10.9), or medical history, if relevant.
If any potential bone safety findings, as per the image review charter, are determined to be 
present in the MRI central read report, then these findings are to be reported to Pfizer Safety 
as an important medical event on the CT SAE form within 24 hours of awareness of the 
event. These potential bone related safety findings are to initially be detailed as potentially 
related to study intervention under study. If subsequently determined (e.g. following further 
history, examination, investigation, adjudication) that the finding is unrelated to study 
intervention, then this must be updated by submitting a follow up CT SAE form within 24 
hours of awareness. 
Incidental/Unrelated Findings:
An incidental finding is one unknown to the participant and has potential health or 
reproductive importance, which is discovered unexpectedly in the course of a research study, 
but is unrelated to the purpose and beyond the aims of the study.
MRI images will be reviewed by a central review facility. The purpose of this review will be 
to further evaluate whether abrocitinib has any potential effects on adolescent bone with 
regard to abnormal finding(s) in knee MRI, but are not a complete medical review of the 
participant. If during the central review process, any other unexpected observation is 
identified and this finding could, in the opinion of the central reviewer, have a significant 
health or reproductive consequence, this finding will be shared on the central read report to 
the Investigator. All follow-up testing and final diagnosis will be left to the discretion of the 
medical professionals at the site or those with an existing physician-patient relationship. 
Identification of such incidental findings during the central review process should not be 
expected, and the site maintains responsibility for performing a general safety review of all 
images as per site protocols. 
Related Findings:
A related finding is one that is judged by the Investigator to be possibly related to study 
intervention.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 108
The Investigator will make a judgment regarding the underlying cause of all treatment 
emergent AEs. If necessary/required, the Investigator may discuss further with orthopedic 
specialist(s) or other relevant specialist(s) to help inform this judgement, but the judgement 
will ultimately be made by the Investigator.
10.10.8.2. Patient-Report Outcomes for the SubStudy
Participants will complete PRO assessments at the relevant substudy visit prior to other 
clinical activities in the main study (eg, laboratory assessments). The PRO assessments 
should be checked for completeness by the study site staff before proceeding further with the 
substudy visit. Compliance with scheduled PRO activities will be monitored. Appropriately 
delegated site staff will oversee the administration of the PRO assessments at site visits to 
ensure protocol compliance, and will transcribe participant responses into the CRF.
10.10.8.2.1. HSS Pedi-FABS
The HSS Pedi-FABS is a validated 8-item instrument designed to quantify the activity level 
of children between 10 and 18 years of age over a 1 month recall period.25 Participants will 
be asked to indicate the frequency and intensity of their athletic activity, level of play, and 
coach/trainer supervision.26 The HSS Pedi-FABS should be completed as per the substudy 
Schedule of Activities (Section 10.10.2). 
Two versions of the PRO will be completed; each regarding a different recall period:

HSS Pedi-FABS (1 month recall)

HSS Pedi-FABS (1 year recall)
If for whatever unanticipated reason a participant is unable to attend the site visit, the PRO 
assessments may be performed remotely in an acceptable manner if permissible by local 
guidelines/regulations. For example, if permissible, the PRO may be securely posted to the 
participant by courier for completion at home and the PRO can subsequently be collected the 
next time the participant attends the site or can be securely posted to site by courier.
10.10.9. Substudy AE Reporting
There are no additional specific requirements for non-serious AE reporting in the substudy. 
The requirements from the main protocol apply. Please refer to the Adverse Event Reporting 
section (Section 8.3) of the main protocol for further details. 
10.10.9.1. Withdrawal From the Substudy Due to AEs
Participants who discontinue from the main study will also be discontinued from the 
substudy. An end of treatment visit will be performed per the main study protocol and 
participants should enter into the follow-up period, with an end of study visit scheduled for 4 
weeks after the end of treatment visit. 
Please refer to Section 7.1 of the main protocol for further details.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 109
10.10.10. Substudy Data Analysis/Statistical Methods
Detailed methodology for summary and statistical analyses of the data collected in this 
substudy will be described in a SAP, which will be maintained by the sponsor.
10.10.10.1. Sample Size Determination
Adolescent participants 12 to <18 years of age in the main study will be eligible for 
enrollment into the substudy.
10.10.10.2. Substudy Efficacy Analysis
There are no efficacy analyses planned for this substudy.
10.10.10.3. Substudy Safety Analyses
Bone safety findings as adjudicated by the safety adjudication committee will be summarized 
by treatment group using frequency and proportions along with 95% CI for the proportions.
Further details will be specified in the SAP.
10.10.10.4. Substudy Interim Analysis
There will be no formal interim analysis for this substudy.  The sponsor may conduct reviews 
of the data, including MRI data, during the course of the study for the purpose of safety 
assessment or to support regulatory submissions.
10.10.11. Substudy Safety Adjudication Committees
To help assess the specific, complex safety events in this substudy, a Safety Adjudication 
Committee consisting of clinical experts in the relevant clinical area will be established 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 Committee can be found in the respective charter, 
including a specific description of the scope of their responsibilities, a plan in which 
communication timelines are defined, and the exact process and definition used by the 
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.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 110
11. REFERENCES
1.
Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and 
adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, 
double-blind, randomised, placebo-controlled, phase 3 trial. Lancet 
2020;396(10246):255-266.
2.
Akdis C, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in 
children and adults: European Academy of Allergology and Clinical 
Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL 
Consensus Report. Allergy 2006;61:969-87.
3.
Weidinger S, Novak N. Atopic dermatitis. Lancet 2016;387:1109-22.
4.
Auriemma M, Vianale G, Amerio P, et al. Cytokines and T cells in atopic dermatitis. 
Eur Cytokine Netw 2013; 24(1):37-44.
5.
Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of 
atopic dermatitis: section 3. Management and treatment with phototherapy and systemic 
agents. J Am Acad Dermatol. 2014;71:327-49.
6.
Johanssen E, Ballardini N, Bergström A, et al. Atopic and nonatopic eczema in 
adolescence: is there a difference? Br J Dermatol. 2015;173:962-8.
7.
Egeberg A, Andersen YM, Gislason GH. Prevalence of comorbidity and associated risk 
factors in adults with atopic dermatitis. Allergy. 2017;72:783-91.
8.
Drucker AM, Wang AR, Li WQ, et al. The burden of atopic dermatitis: Summary of a 
report for the National Eczema Association. J Invest Dermatol. 2017;137:26-30
9.
Eckert L, Gupta S, Amand C, et al. Impact of atopic dermatitis on health-related quality 
of life and productivity in adults in the United States: An analysis using the National 
Health and Wellness Survey. J Am Acad Dermatol. 2017;77:274-9.
10.
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 
1980;(Suppl 92):44-7.
11.
Yosipovitch G, Reaney M, Mastey V, et al. Validation of the peak pruritus numerical 
rating scale: Results from clinical studies of dupilumab in adult patients with moderate 
to severe atopic dermatitis. J Am Acad Dermatol 2017;76:AB278.
12.
Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: 
psychometric validation and responder definition for assessing itch in moderate-to-
severe atopic dermatitis. Br J Dermatol 2019;181(4):761-9.
13.
Charman C, Venn A, Williams HC. The Patient-Oriented Eczema Measure: 
development and initial validation of a new tool for measuring atopic eczema severity 
from the patients’ perspective. Arch Dermatol 2004;140(12)(Dec):1513-9.

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 111
14.
Charman CR, Venn AJ, Ravenscroft JC, et al.. Translating Patient-Oriented Eczema 
Measure (POEM) scores into clinical practice by suggesting severity strata derived 
using anchor-based methods. Br J Dermatol 2013;169(6)(Dec):1326-32.
15.
Spuls PI, Gerbens LAA, Simpson E, et al. Patient-Oriented Eczema Measure (POEM), a 
core instrument to measure symptoms in clinical trials: a Harmonising Outcome 
Measures for Eczema (HOME) statement. Br J Dermatol 2017;176(4)(Apr):979-84.
16.
Pariser DM, Simpson EL, Gadkari A, et al. Evaluating patient-perceived control of 
atopic dermatitis: design, validation, and scoring of the Atopic Dermatitis Control Tool 
(ADCT). Curr Med Res Opin. 2020;36(3):367-376.
17.
Simpson E, Eckert L, Gadkari A, et al. Validation of the Atopic Dermatitis Control Tool 
(ADCT©) using a longitudinal survey of biologic-treated patients with atopic 
dermatitis. BMC Dermatol. 2019 Nov 6;19(1):15.
18.
Posner K, Oquendo MA, Gould M, et al. Columbia Classification Algorithm of Suicide 
Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal 
risk analysis of antidepressants. Am J Psychiatry 2007; 164(7):1035-43.
19.
Olumiant® (baricitinib) Prescribing Information. Indianapolis, IN: Lilly LLC; Revised 
October 2019. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207924s001lbl.pdf. 
Accessed: 13 April 2020.
20.
RINVOQ™ (upadacitanib) Prescribing Information. Sligo, Ireland: AbbVie Inc; August 
2019. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf. 
Accessed: 13 April 2020.
21.
Mukovozov IM, Morra DE, Giustini D et al. Atopic dermatitis and bone health: a 
systematic review. J Eur Acad Dermatol Venereol, 2020; 35: 615-628.
22.
Kim NN, Parker RM, Weinbauer GF, et al. Points to consider in designing and 
conducting juvenile toxicology studies. Int J Toxicol 2017;36(4):325-39.
23.
Johannsson G, Bidlingmaier M, Biller BM, et al. Growth Hormone Research Society 
perspective on biomarkers of GH action in children and adults. Endocrine Connections 
2018;7(3):R126-34.
24.
Faulkner RA, Davison KS, Bailey DA, et al. Size-corrected BMD decreases during 
peak linear growth: Implications for fracture incidence during adolescence. J Bone 
Miner Res 2006;21(12):1864-70.
25.
Fabricant PD, Suryavanshi JR, Calcei JG, et al. The Hospital for Special Surgery 
Pediatric Functional Activity Brief Scale (HSS Pedi-FABS): Normative Data. Am J 
Sports Med. 2018 Apr;46(5):1228-34. 

Abrocitinib
Protocol B7451094
Protocol Amendment 1, 23 March 2022
PFIZER CONFIDENTIAL
Page 112
26.
Fabricant PD, Robles A, Downey-Zayas T, et al. Development and Validation of a 
Pediatric Sports Activity Rating Scale: The Hospital for Special Surgery Pediatric 
Functional Activity Brief Scale (HSS Pedi-FABS). The American Journal of Sports 
Medicine. 2013;41(10):2421-9.