Conditions: Atopic Dermatitis Plaque Psoriasis
Keywords: atopic dermatitis, plaque psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 104
Healthy volunteers: no

Brief summary:
This study is being conducted to provide data on efficacy, safety, tolerability and PK of PF-07038124 ointment versus vehicle control in the treatment of mild to moderate AD and mild to moderate plaque psoriasis.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None arm 4: None

Interventions: intervention 1: PF-07038124 ointment intervention 2: Vehicle ointment
Intervention descriptions: intervention 1: PF-07038124 ointment at 0.01% with QD dosing for 6 weeks intervention 2: Vehicle ointment with QD dosing for 6 weeks

Protocol document:
Prot_000.pdf: 
PF-07038124
Protocol C3941002
Final Protocol, 19 August 2020 
PFIZER CONFIDENTIAL
Page 1
A PHASE 2A, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, 
PARALLEL GROUP STUDY TO ASSESS THE EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-07038124 OINTMENT FOR 
6 WEEKS IN PARTICIPANTS WITH MILD TO MODERATE ATOPIC 
DERMATITIS OR PLAQUE PSORIASIS
Study Intervention Number:
PF-07038124
Study Intervention Name:
N/A
US IND Number:
EudraCT Number:
2020-003977-23
Protocol Number:
C3941002
Phase:
2a
Short Title: A Phase 2a, randomized, double-blind, vehicle-controlled, parallel group 
study to assess efficacy, safety, tolerability and pharmacokinetics of PF-07038124 
ointment in participants with atopic dermatitis or plaque psoriasis
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
19 August 2020
N/A
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
1. PROTOCOL SUMMARY...................................................................................................11
1.1. Synopsis ..................................................................................................................11
1.2. Schema ....................................................................................................................17
1.3. Schedule of Activities .............................................................................................18
1.3.1. Atopic Dermatitis........................................................................................18
1.3.2. Psoriasis......................................................................................................22
2. INTRODUCTION ...............................................................................................................26
2.1. Study Rationale .......................................................................................................26
2.2. Background .............................................................................................................26
2.2.1. Role of Proinflammatory Cytokines in AD and Psoriasis..........................26
2.2.2. Description of Investigational Product: Mechanism of Action ..................27
2.2.3. Preclinical Safety Data ...............................................................................28
2.3. Benefit/Risk Assessment.........................................................................................31
2.3.1. Risk Assessment.........................................................................................32
2.3.2. Benefit Assessment.....................................................................................33
2.3.3. Overall Benefit/Risk Conclusion................................................................33
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................34
3.1. Atopic Dermatitis ....................................................................................................34
3.2. Psoriasis...................................................................................................................36
4. STUDY DESIGN.................................................................................................................39
4.1. Overall Design.........................................................................................................39
4.2. Scientific Rationale for Study Design.....................................................................39
4.2.1. Participant Input into Design......................................................................40
4.3. Justification for Dose ..............................................................................................40
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4.4. End of Study Definition ..........................................................................................42
5. STUDY POPULATION......................................................................................................42
5.1. Inclusion Criteria.....................................................................................................42
5.1.1. General Inclusion Criteria Applicable for both AD and psoriasis..............42
5.1.2. Disease-Specific Inclusion Criteria ............................................................43
5.1.2.1. AD Specific Inclusion Criteria..................................................43
5.1.2.2. Psoriasis Specific Inclusion Criteria .........................................43
5.2. Exclusion Criteria....................................................................................................43
5.3. Lifestyle Considerations..........................................................................................46
5.3.1. Contraception..............................................................................................46
5.3.2. Dietary Supplements...................................................................................46
5.3.3. Medications/Treatments Discontinuation, Non-Medicated Emollients .....46
5.3.4. Other Lifestyle Requirements.....................................................................47
5.4. Screen Failures ........................................................................................................48
6. STUDY INTERVENTION..................................................................................................49
6.1. Study Intervention Administered ............................................................................49
6.1.1. Administration............................................................................................49
6.1.1.1. Treatable Areas .........................................................................49
6.2. Preparation/Handling/Storage/Accountability ........................................................51
6.2.1. Preparation and Dispensing........................................................................52
6.2.2. Investigational Product Accountability ......................................................53
6.2.3. Destruction of Investigational Product Supplies ........................................53
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................54
6.3.1. Allocation to Study Intervention ................................................................54
6.3.2. Breaking the Blind......................................................................................54
6.4. Study Intervention Compliance...............................................................................55
6.5. Concomitant Therapy..............................................................................................55
6.5.1. Rescue Medicine.........................................................................................56
6.6. Dose Modification...................................................................................................56
6.7. Intervention After the End of the Study..................................................................56
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................56
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7.1. Discontinuation of Study Intervention ....................................................................56
7.1.1. Temporary Discontinuation........................................................................58
7.1.2. Rechallenge.................................................................................................58
7.2. Participant Discontinuation/Withdrawal from the Study........................................58
7.2.1. Withdrawal of Consent...............................................................................59
7.3. Lost to Follow-up....................................................................................................59
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................60
8.1. Efficacy Assessments..............................................................................................61
8.1.1. Rater Qualifications....................................................................................61
8.1.2. Physician Assessments for AD...................................................................61
8.1.2.1. Eczema Area and Severity Index (EASI)..................................61
8.1.2.2. Investigator’s Global Assessment (IGA) ..................................64
8.1.2.3. BSA with AD ............................................................................65
8.1.3. Patient Reported Outcome Measures for AD.............................................65
8.1.3.1. Peak Pruritus Numerical Rating Scale (PP-NRS) for AD.........66
8.1.4. Physician Assessments for Psoriasis ..........................................................67
8.1.4.1. Psoriasis Area and Severity Index (PASI) ................................67
8.1.4.2. Physician Global Assessment....................................................70
8.1.4.3. BSA with Psoriasis....................................................................70
8.1.5. Patient Reported Outcome Measures for Psoriasis.....................................71
8.1.5.1. Psoriasis Symptom Inventory (PSI) for Psoriasis .....................71
8.2. Safety Assessments .................................................................................................72
8.2.1. Medical History ..........................................................................................72
8.2.2. Physical Examinations (Including Height and Weight) .............................73
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8.2.3. Vital Signs ..................................................................................................74
8.2.4. Electrocardiograms.....................................................................................74
8.2.5. Clinical Safety Laboratory Assessments ....................................................75
8.2.6. Suicidal Ideation and Behavior Risk Monitoring - Columbia Suicide 
Severity Rating Scale (C-SSRS)......................................................................75
8.2.7. Local Tolerability Assessment ...................................................................76
8.2.8. Pregnancy Testing ......................................................................................76
8.3. Adverse Events and Serious Adverse Events..........................................................77
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......77
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................78
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................78
8.3.2. Method of Detecting AEs and SAEs ..........................................................78
8.3.3. Follow-up of AEs and SAEs.......................................................................78
8.3.4. Regulatory Reporting Requirements for SAEs...........................................79
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................79
8.3.5.1. Exposure During Pregnancy......................................................79
8.3.5.2. Exposure During Breastfeeding ................................................81
8.3.5.3. Occupational Exposure .............................................................81
8.3.6. Cardiovascular and Death Events...............................................................81
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................82
8.3.8. Adverse Events of Special Interest.............................................................82
8.3.8.1. Lack of Efficacy........................................................................82
8.3.9. Medical Device Deficiencies......................................................................82
8.3.10. Medication Errors.....................................................................................82
8.4. Treatment of Overdose............................................................................................83
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8.9. Immunogenicity Assessments.................................................................................86
8.10. Health Economics .................................................................................................86
9. STATISTICAL CONSIDERATIONS ................................................................................86
9.1. Estimands and Statistical Hypotheses.....................................................................87
9.1.1. Estimands for AD .......................................................................................87
9.1.2. Estimands for Psoriasis...............................................................................87
9.2. Sample Size Determination.....................................................................................88
9.2.1. Sample Size Determination for AD............................................................88
9.2.2. Sample Size Determination for Psoriasis ...................................................88
9.3. Analysis Sets ...........................................................................................................89
9.4. Statistical Analyses .................................................................................................89
9.4.1. Efficacy Analyses for AD...........................................................................89
9.4.2. Efficacy Analyses for Psoriasis ..................................................................90
9.4.3. Safety Analyses ..........................................................................................91
9.4.3.1. Electrocardiogram Analyses......................................................92
9.5. Interim Analyses .....................................................................................................92
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............92
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................93
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............93
10.1.1. Regulatory and Ethical Considerations ....................................................93
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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................93
10.1.2. Financial Disclosure .................................................................................94
10.1.3. Informed Consent Process ........................................................................94
10.1.4. Data Protection .........................................................................................95
10.1.5. Dissemination of Clinical Study Data ......................................................95
10.1.6. Data Quality Assurance ............................................................................97
10.1.7. Source Documents....................................................................................98
10.1.8. Study and Site Start and Closure ..............................................................98
10.1.9. Publication Policy.....................................................................................99
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................100
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................101
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................102
10.3.1. Definition of AE .....................................................................................102
10.3.2. Definition of SAE...................................................................................103
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.....................105
10.3.4. Reporting of SAEs..................................................................................108
10.4. Appendix 4: Contraceptive Guidance .................................................................109
10.4.1. Male Participant Reproductive Inclusion Criteria..................................109
10.4.2. Female Participant Reproductive Inclusion Criteria...............................109
10.4.3. Woman of Childbearing Potential ..........................................................109
10.4.4. Contraception Methods...........................................................................110
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
and Study Intervention Rechallenge Guidelines .....................................................113
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................115
10.8. Appendix 8: Country-Specific Requirements .....................................................117
10.9. Appendix 9: Alternative Measures During Public Emergencies ........................118
10.9.1. Telehealth Visits.....................................................................................118
10.9.2. Alternative Facilities for Safety Assessments ........................................119
10.9.2.1. Laboratory Testing ................................................................119
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10.9.2.2. Electrocardiograms................................................................119
10.9.3. Study Intervention ..................................................................................119
10.9.4. Home Health Visits.................................................................................120
10.9.5. Adverse Events and Serious Adverse Events.........................................121
10.9.6. Efficacy Assessments .............................................................................121
10.9.7. Independent Oversight Committees .......................................................121
10.10. Appendix 10: Prohibited Prior and Concomitant Medications .........................122
10.10.1. Prohibited Prior and Concomitant Medications ...................................122
10.10.2. Prohibited Concomitant Medications which may result in Drug-
Drug Interaction (DDI) ..................................................................................124
10.11. Appendix 11: Diagnosis Criteria for AD ..........................................................125
10.12. Appendix 12: Abbreviations .............................................................................126
11. REFERENCES ................................................................................................................130
LIST OF TABLES
Table 1.
Study Intervention Groups........................................................................15
Table 4.
Proposed Doses, Predicted Free Exposures, and Safety Margins 
following QD Topical Application of PF-07038124a...............................41
Table 5.
Clinical Sign Severity Scoring Criteria for EASI.....................................62
Table 6.
Handprint Determination of Body Region Surface Area for AD.............63
Table 7.
EASI Area Score Criteria .........................................................................63
Table 8.
EASI Body Region Weighting .................................................................63
Table 9.
Investigator’s Global Assessment (IGA) Score........................................64
Table 10.
Component Scoring Criteria for PASI*....................................................68
Table 11.
Handprint Determination of Body Region Surface Area for 
Psoriasis....................................................................................................68
Table 12.
PASI Area Score Criteria..........................................................................69
Table 13.
PASI Body Region Weighting..................................................................69
Table 14.
Physician Global Assessment (PGA) Score .............................................70
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Table 16.
Protocol-Required Safety Laboratory Assessments ...............................101
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A Phase 2a, randomized, double blind, vehicle controlled, parallel group study 
to assess efficacy, safety, tolerability and pharmacokinetics of PF-07038124 ointment in 
participants with atopic dermatitis (AD) or plaque psoriasis.
Rationale: This multicenter, randomized, double blind, vehicle controlled, parallel group, 
study is being conducted to provide data on efficacy, safety, tolerability and PK of 
PF-07038124 ointment versus vehicle control in the treatment of mild to moderate AD and 
mild to moderate plaque psoriasis.  This is the first study where PF-07038124 ointment is 
being administered to participants with AD or psoriasis. 
Objectives, Estimands, and Endpoints
ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
Primary Objective 
Primary Endpoint(s)
Primary Estimands 
•
To compare the efficacy of 
PF-07038124 versus 
vehicle on percent change 
from baseline in Eczema
Area and Severity Index 
(EASI) in participants with 
mild or moderate atopic 
dermatitis (AD).
•
Percent change from baseline in 
EASI total score at Week 6.
•
Estimand E1: This 
estimand is intended to 
provide a population level 
estimate of the treatment 
effect of the investigational 
product (IP) on a 
continuous endpoint; 
without the benefit of 
additional prohibited 
medications during 
treatment and regardless of 
participant compliance 
with the IP dosing.
Secondary Objective(s): 
Secondary Endpoints
Secondary Estimands 
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using Investigator’s Global 
Assessment (IGA) score 
assessment as endpoint in 
participants with mild or 
moderate AD.
•
Proportion of participants 
achieving IGA score of clear (0) or 
almost clear (1) (on a 5-point
scale) and a reduction from 
baseline of ≥2 points at Week 6.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the 
IP on a binary responder 
endpoint; without the 
benefit of additional 
prohibited medications and 
regardless of a participant 
compliance with the IP 
dosing.
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ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of disease 
severity and symptoms as 
endpoints in participants 
with mild or moderate AD.
•
Proportion of participants 
achieving EASI 75 
(75% improvement from baseline)
at study visit time points specified 
in the SoA.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the 
IP on a binary responder 
endpoint; without the 
benefit of additional 
prohibited medications and 
regardless of a participant.
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of patient 
reported outcomes (PRO), in 
participants with mild or 
moderate AD.
•
Proportion of participants having 
≥4 points of reduction in weekly 
averages of Peak Pruritus 
Numerical Rating Scale (PP-NRS) 
from baseline at study visit time 
points specified in the SoA.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the 
IP on a binary responder 
endpoint; without the 
benefit of additional 
prohibited medications and 
regardless of a participant.
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
on measures of disease and 
symptom severity in 
participants with mild or 
moderate AD.
•
Change from baseline in EASI 
total score at study visit time points 
specified in the SoA.
•
Proportion of participants 
achieving IGA score of clear (0) or 
almost clear (1) at study visit time
points specified in the SoA.
•
Percent change from baseline in 
body surface area (BSA) at study 
visit time points specified in the 
SoA.
•
All continuous secondary 
endpoints will be analyzed 
descriptively and using 
estimand E1 described 
above, when appropriate.
•
All categorical secondary 
endpoints will be analyzed 
descriptively and using 
estimand E2 described 
above, when appropriate.
•
To characterize the safety 
and tolerability of 
PF-07038124 versus vehicle 
in participants with mild or 
moderate AD.  
• Incidence of treatment emergent 
adverse events (AEs) and serious 
adverse events (SAEs), clinically 
significant changes in vital signs, 
electrocardiogram (ECG), and 
laboratory tests.
•
Incidence of severity grades in skin
tolerability at study visit time points 
specified in the SoA.
•
There is no defined 
estimand for these 
endpoints and they will be 
analyzed using Pfizer data 
standards as applicable.
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PSORIASIS
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on change from baseline in 
Psoriasis Area and Severity 
Index (PASI) score in 
participants with mild to 
moderate plaque psoriasis. 
•
Change from baseline in 
PASI score at Week 6.
•
Estimand E1: This estimand is 
intended to provide a population 
level estimate of the treatment 
effect of the investigational 
product (IP) alone on a 
continuous endpoint; without the 
benefit of additional prohibited 
medications, regardless of 
participants compliance with the 
IP dosing.
Secondary: 
Secondary: 
Secondary:
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on Physician Global
Assessment (PGA) score in 
participants with mild to 
moderate plaque psoriasis.
•
Proportion of participants 
with PGA score of clear (0) 
or almost clear (1) (on a 
5-point scale) and ≥2 points 
improvement from baseline 
at Week 6. 
•
Estimand E2: This estimand is 
intended to provide a 
population level estimate of the 
treatment effect of the IP alone 
on a binary responder 
endpoint; without the benefit of 
additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on the proportion of 
participants with mild to 
moderate plaque psoriasis 
achieving PASI 75. 
•
Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from 
baseline) at study visit time 
points specified in the SoA.
•
Estimand E2: This estimand is 
intended to provide a 
population level estimate of the 
treatment effect of the IP alone 
on a binary responder 
endpoint; without the benefit of 
additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus 
vehicle, using measures of 
patient reported outcomes 
(PRO), in participants with 
mild or moderate plaque 
psoriasis.
•
Proportion of participants 
who achieved a Psoriasis 
Symptoms Inventory (PSI)
score of 0 (not at all) or 
1 (mild) on every item at 
study visit time points 
specified in the SoA.
•
Estimand E2: This estimand is 
intended to provide a population 
level estimate of the treatment 
effect of the IP alone on a binary 
responder endpoint; without the 
benefit of additional prohibited 
medications, regardless of 
participants compliance with the 
IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on measures of disease and 
symptom severity in 
participants with mild to 
•
Change from baseline in 
PASI scores at study visit 
time points specified in the 
SoA (except Week 6). 
•
Percent change from baseline 
•
All other continuous secondary 
endpoints will be analyzed 
descriptively and using estimand 
E2 described above when 
appropriate.
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PSORIASIS
Objectives
Endpoints
Estimands
moderate plaque psoriasis. 
in PASI scores at study visit 
time points specified in the 
SoA.
•
Proportion of participants 
with PGA score clear (0) or 
almost clear (1) and ≥2 points 
improvement from baseline 
at time points specified in the 
SoA.
•
Percent change from baseline 
in BSA at study visit time 
points specified in the SoA.
•
All other categorical secondary 
endpoints will be analyzed 
descriptively and using estimand 
E1 described above when 
appropriate.
•
To assess safety and 
tolerability of PF-07038124 
in participants with mild to 
moderate plaque psoriasis.
•
Incidence of treatment
emergent adverse events 
(AEs) and serious adverse 
events (SAEs), clinically 
significant changes in vital 
signs, electrocardiogram 
(ECG), and laboratory tests.
•
Incidence of severity grades 
in skin tolerability at times 
indicated in SoA.
•
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data 
standards as applicable.
Overall Design
This is a Phase 2a, randomized, double-blind, vehicle-controlled, parallel group, multicenter
study in the adult participants with mild to moderate AD or mild to moderate plaque 
psoriasis. The study will assess the efficacy, safety, tolerability, and PK of PF-07038124
ointment. 
Number of Participants
A total of approximately 88 participants with AD or psoriasis will be randomly assigned to 
study intervention in this basket trial.
For AD, a maximum of approximately 56 participants will be randomly assigned to study 
intervention such that approximately 42 evaluable participants complete the study. 
Assuming a 25% drop out rate, approximately 28 participants will be randomized to either 
PF-07038124 or vehicle control to achieve approximately 21 completers in each group.
Randomization will be stratified by baseline disease severity (mild [Investigator's Global 
Assessment or IGA = 2] vs. moderate [IGA = 3]). Up to 25% of AD participants will have 
an IGA score of 2 at baseline. 
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For psoriasis, a maximum of approximately 32 participants will be randomly assigned to 
study intervention such that approximately 24 evaluable participants complete the study.  
Assuming a 25% drop out rate, approximately 16 participants will be randomized to 
PF-07038124 or vehicle control to achieve 12 completers in each group. Randomization will
be stratified by baseline disease severity (mild [Physician Global Assessment or PGA = 2]
vs. moderate [PGA = 3]). Up to 25% of psoriasis participants will have a PGA score of 2 at 
baseline. 
Intervention Groups and Duration
The total duration of study participation will be approximately 17 weeks, including a 
screening period of up to 6 weeks, a double-blind treatment period of 6 weeks, and a safety
follow-up period of 4-5 weeks from last dose of study drug to last study visit. 
Study intervention arms are shown in the following table.  
Table 1.
Study Intervention Groups
Study Intervention 
Group (Indication)
Target Number 
of Participants 
Randomized
Approx. Number 
of Completers
Study Intervention
A (atopic dermatitis)
28
21
PF-07038124 ointment at 0.01% with QD 
dosing for 6 weeks
B (atopic dermatitis)
28
21
Vehicle ointment with QD dosing for 
6 weeks
C (plaque psoriasis)
16
12
PF-07038124 ointment at 0.01% with QD 
dosing for 6 weeks
D (plaque psoriasis)
16
12
Vehicle ointment with QD dosing for 
6 weeks
The study intervention for AD and psoriasis participants are the same.
A study design schematic is presented in Section 1.2.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
Statistical Methods for AD
The primary estimand will be estimated population-based average treatment effect on percent 
change from baseline in Eczema and Severity Index (EASI) score relative to vehicle at 
6 weeks for all randomized participants in the absence of prohibited medication without 
regard to compliance.
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The secondary estimand will be the estimated population-based average treatment effect on
the rates of Investigator’s Global Assessment (IGA) response (percentage of participants
with a score of 0 or 1 and a 2 point or greater decrease from baseline) at Week 6 relative to
vehicle without regard to compliance with Investigational Product (IP) in the absence of 
prohibited medication.
All other secondary continuous clinical endpoints will be analyzed using the primary
estimand, while all other secondary categorical clinical endpoints will be analyzed using the
secondary estimand described above. Other estimands may be used for some of the primary 
and secondary endpoints to examine the robustness of the results and to compare to available 
literature as needed. Details of these analyses will be presented in the Statistical Analysis 
Plan (SAP).
Statistical Methods for Psoriasis
The primary estimand will be the population average treatment effect on change from
baseline in Psoriasis Area and Severity Index (PASI) scores at Week 6 relative to vehicle
without regard to compliance in the absence of prohibited medication. Measurements after 
the initiation of prohibited medication will be censored and treated as missing data.
The secondary estimand will be the population average treatment effect on the Physician 
Global Assessment (PGA) response rate: percentage of participants with a score of clear (0) 
or almost clear (1) and a 2 point or greater improvement from baseline at Week 6 relative to
vehicle without regard to compliance with IP in the absence of prohibited medication.
All other secondary continuous clinical endpoints will be analyzed using the primary
estimand, while all other secondary categorical clinical endpoints will be analyzed using the 
secondary estimand described above. Other estimands may be used for some of the primary 
and secondary endpoints to examine the robustness of the results and to compare to available 
literature as needed. Details of these analyses will be presented in the SAP.
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1.2. Schema
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
1.3.1. Atopic Dermatitis
ATOPIC DERMATITIS
Visit Identifiera
Screening & 
Washout
Day 1
(Baseline)
Week 1
Week 2
Week 4
Week 6
(EOT)
Follow-up
(EOS)
Early 
Termination (ET)
Visit Window
Day-42 to -1
N/A
Day 8
±2
Day 15
±2
Day 29
±2
Day 43
±2
28–35 Days 
post-last Dose
N/A
Visit Number
1
2
3
4
5
6
7
N/A
Enrollment Procedures
Informed Consent
X
Register Subject Using IRT System
X
Medical History
X
X
Concomitant/Prior Treatments
X
X
X
X
X
X
X
X
Demography
X
Eligibility Assessment
X
X
Randomization
X
Clinical Assessments
Complete Physical Examinationb
X
X
X
Targeted Physical Examinationb
X
X
X
X
X
Weight
X
X
Height
X
Vital Signsc
X
X
X
X
X
X
ECGd
X
X
X
C-SSRSe
X
Laboratory Assessments
Serum FSH (WONCBP only) or Serum 
Pregnancy Test (WOCBP only)f
X
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ATOPIC DERMATITIS
Visit Identifiera
Screening & 
Washout
Day 1
(Baseline)
Week 1
Week 2
Week 4
Week 6
(EOT)
Follow-up
(EOS)
Early 
Termination (ET)
Visit Window
Day-42 to -1
N/A
Day 8
±2
Day 15
±2
Day 29
±2
Day 43
±2
28–35 Days 
post-last Dose
N/A
Visit Number
1
2
3
4
5
6
7
N/A
Urine Pregnancy Test (conducted at 
study site)g
X
X
X
X
X
X
X
Hematology, Chemistry and Urinalysish
X
X
X
X
X
X
X
X
Fibrinogen, hsCRPh
X
X
X
X
X
X
X
X
IP Related Processes
Dispense dosing diary/PROs and 
instruct on usage
X
Assess BSA & calculate IP need
X
X
X
X
X
Body Map
X
X
X
X
X
Weigh and dispense IP
X
X
X
X
IP application and observation (at site/at 
home in case of Home Health Visits)
X
X
X 
X 
X
Record dose and time of IP application 
in dosing diary 
X
→
→
→
X
Collect and weigh returned IP tubes for 
compliance check
X
X 
X 
X
X
Review of dosing diary/PROs
X
X
X 
X 
X
X
X
Collect dosing diary/PROs
Xk
X
X
AD-Related Clinical Assessments
EASI
X
X
X
X 
X
X
X
X
IGA
X
X
X
X 
X
X
X
X
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ATOPIC DERMATITIS
Visit Identifiera
Screening & 
Washout
Day 1
(Baseline)
Week 1
Week 2
Week 4
Week 6
(EOT)
Follow-up
(EOS)
Early 
Termination (ET)
Visit Window
Day-42 to -1
N/A
Day 8
±2
Day 15
±2
Day 29
±2
Day 43
±2
28–35 Days 
post-last Dose
N/A
Visit Number
1
2
3
4
5
6
7
N/A
BSA
X
X
X
X
X
X
X
X
Safety Monitoring
Contraception check
X
X
X
X 
X 
X
X
X
Local Tolerability Assessmentsl
X
X
X
X
X
X
X
Serious and non-serious AE monitoring
X
→
→
→
→
→
X
X
Patient Reported Outcomes (PRO) 
In-clinic completion
At-home completion
PP-NRSm
X
→
→
X
X
X
X
X
Abbreviations: →= ongoing/continuous event; AD = Atopic Dermatitis; BSA = Body Surface Area; 
 C-SSRS = Columbia Suicide 
Severity Rating Scale;
EASI = Eczema Assessment Severity Index; ECG = electrocardiogram; EOS = End of Study; EOT = End of 
Treatment; ET = Early termination; FSH = Follicle Stimulating Hormone; hsCRP= High-sensitivity C-reactive protein (hsCRP); IGA = Investigator’s Global Assessment; 
 IP = Investigational Product; PD = Pharmacodynamics; 
 
; PP-NRS = Peak Pruritis Numerical Rating Scale; PRO = Patient Reported 
Outcomes; 
.
a.
Day relative to start of study treatment (Day 1). Except for Screening Visit and Day 1 Visit, Alternative Measures (Section 10.9) may be implemented in case of public 
emergencies. Please refer to Section 10.9 for the details about the assessments that may be performed during a Telehealth Visit (including Efficacy Assessments) or a Home 
Health Visit.
b.
Physical Examination: Physical assessments may be performed in the event of Home Health Visit.
c.
Vital Signs: Temperature (Oral or tympanic temperature), pulse rate, and blood pressure will be taken in supine position, after the participant has been lying calmly for a 
minimum of 5 minutes.  Assessment of vital signs should precede blood draw for clinical laboratory tests.
d.
Local read, single ECG (in supine position) at all time points indicated.  To ensure safety of the participant, a qualified individual (eg, sub-investigator) at the investigator site 
will make comparisons to baseline measurements taken at Day 1. Triplicate ECG will be conducted as appropriate per Section 8.2.4.
e.
Site staff is to administer the Columbia Suicide Severity Rating Scale (C-SSRS) to all participants at screening and score immediately.  Participants who have recent or active 
suicidal ideation or behavior or clinically significant depression will be excluded from the study per Section 5.2.
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f.
Serum FSH (WONCBP only) or Serum Pregnancy test (WOCBP only): For Women of Non-Childbearing Potential (WONCBP), serum follicle stimulating hormone (FSH) 
test to be performed at Screening to confirm postmenopausal status in female subjects who have been amenorrheic for at least 12 consecutive months. Serum Pregnancy test 
is required for all Women of Childbearing Potential (WOCBP).
g.
Urine Pregnancy Tests must be performed prior to dosing with the investigational product for female subjects of childbearing potential. Two negative pregnancy tests are 
required before receiving investigational product (1 negative Serum Pregnancy Test at screening and 1 negative Urine Pregnancy Tests at the baseline visit before 
investigational product administration). 
h.
Blood draw for Protocol-Required Safety Laboratory Assessments (Appendix 2) on Day 1 will be performed before the in-clinic IP application.  Laboratory tests with 
abnormal results may be repeated once during the screening period; the last value will be used to determine eligibility. 
k.
Only for participants who do not meet eligibility criteria.
l.
Local tolerability at the site of IP application will be assessed pre-dose and immediately after post-dose.
m.
PP-NRS: At the screening visit or at least 7 days prior to Day 1, site staff will dispense the ePRO device (or paper PROs) and review instructions for completion.
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1.3.2. Psoriasis
PSORIASIS
Visit Identifiera
Screening & 
Washout
Day 1
(Baseline)
Week 1
Week 2
Week 4
Week 6
(EOT)
Follow-up
(EOS)
Early Termination 
(ET)
Visit Window
Day -42 to -1
N/A
Day 8±2
Day 15±2
Day 29±2
Day 43±2
28–35 Days 
post-last Dose
N/A
Visit Number
1
2
3
4
5
6
7
N/A
Informed Consent
X
Register Subject Using IRT System
X
Medical History 
X
X
Concomitant/Prior Treatments
X
X
X
X
X
X
X
X
Demography
X
Eligibility Assessment
X
X
Randomization
X
Clinical assessments 
Complete Physical Examinationb
X
X
X
Targeted Physical Examinationb
X
X
X
X
X
Weight
X
X
Height
X
Vital Signsc
X
X
X
X
X
X
ECGd
X
X
X
C-SSRSe
X
Laboratory assessments
Serum FSH (WONCBP only) or Serum 
Pregnancy Test (WOCBP only)f
X
Urine Pregnancy Test (conducted at 
study site)g
X
X
X
X
X
X
X
Hematology, Chemistry and Urinalysish
X
X
X
X
X
X
X
X
Fibrinogen, hsCRPh
X
X
X
X
X
X
X
X
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PSORIASIS
Visit Identifiera
Screening & 
Washout
Day 1
(Baseline)
Week 1
Week 2
Week 4
Week 6
(EOT)
Follow-up
(EOS)
Early Termination 
(ET)
Visit Window
Day -42 to -1
N/A
Day 8±2
Day 15±2
Day 29±2
Day 43±2
28–35 Days 
post-last Dose
N/A
IP Related Processes
Dispense dosing diary/PROs and 
instruct on usage
X
BSA & calculate IP need
X
X
X
X
X
Body Map
X
X
X
X
X
Weigh and dispense IP
X
X
X
X
IP application and observation (at site/at 
home in case of Home Health Visits)
X
X
X 
X 
X
Record dose and time of IP application 
in dosing diary 
X
→
→
→
X
Collect and weigh returned IP tubes for 
compliance check
X
X 
X 
X
X
Review of dosing Diary/PROs
X
X
X 
X 
X
X
X
Collect dosing Diary/PROs
Xk
X
X
Psoriasis-Related Clinical assessments
PASI
X
X
X
X
X
X
X
X
PGA
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
Safety Monitoring
Contraception check
X
X
X
X
X
X
X
X
Local Tolerability Assessmentsl
X
X
X
X
X
X
X
Serious and non-serious AE monitoring
X
→
→
→
→
→
→
X
Patient Reported Outcomes (PRO) 
In-clinic completion
At-home completion
PSIm
X
→
→
X
X
X
X
X
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Abbreviations: →= ongoing/continuous event; BSA = Body Surface Area; C-SSRS = Columbia Suicide Severity Rating Scale; 
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; ET = Early Termination; FSH = Follicle Stimulating Hormone; hsCRP= High-sensitivity C-reactive 
protein (hsCRP); 
; IP = Investigational Product; PASI = Psoriasis Area and Severity index; PGA = Physicians Global Assessment; 
 
; PRO = Patient Reported Outcomes; PSI=Psoriasis Symptom Inventory.
a.
Day relative to start of study treatment (Day 1). Except for Screening Visit and Day 1 Visit, alternative measures (Section 10.9) may be implemented in case of public 
emergencies. Please refer to Section 10.9 for the details about the assessments that may be performed during a Telehealth Visit (including Efficacy Assessments) or a Home 
Health Visit.
b.
Physical Examination: Physical assessments may be performed in the event of Home Health Visit.
c.
Vital Signs: Temperature (Oral or tympanic temperature), pulse rate, and blood pressure will be taken in supine position, after the participant has been lying calmly for a 
minimum of 5 minutes.  Assessment of vital signs should precede blood draw for clinical laboratory tests.
d.
Local read, single ECG (in supine position) at all time points indicated. To ensure safety of the participant, a qualified individual (eg, sub-investigator) at the investigator site 
will make comparisons to baseline measurements taken at Day 1. Triplicate ECG will be conducted as appropriate per Section 8.2.4.
e.
Site staff is to administer the Columbia Suicide Severity Scale (C-SSRS) to all participants at screening and score immediately.  Participants who have recent or active 
suicidal ideation or behavior or clinically significant depression will be excluded from the study.
f.
Serum FSH (WONCBP only) or Serum Pregnancy test: For Women of Non-Childbearing Potential (WONCBP), serum follicle stimulating hormone (FSH) test to be 
performed at Screening to confirm postmenopausal status in female subjects who have been amenorrheic for at least 12 consecutive months. Serum Pregnancy test is required 
for all Women of Childbearing Potential (WOCBP).
g.
Urine Pregnancy Tests must be performed prior to dosing with the investigational product for female subjects of childbearing potential. Two negative pregnancy tests are 
required before receiving investigational product (1 negative Serum Pregnancy Test at screening and 1 negative Urine Pregnancy Tests at the baseline visit before 
investigational product administration).
h.
Blood draw for Protocol-Required Safety Laboratory Assessments (Appendix 2) on Day 1 will be performed before the in-clinic IP application.  Laboratory tests with 
abnormal results may be repeated once during the screening period; the last value will be used to determine eligibility. 
k.
Only for participants who do not meet eligibility criteria.
l.
Local tolerability at the site of IP application will be assessed pre-dose and immediately after post-dose.
m.
PSI: At the screening visit or at least 7 days prior to Day 1, site staff will dispense the ePRO device (or paper PROs) and review instructions for completion.
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2. INTRODUCTION
PF-07038124 is a topical phosphodiesterase 4 (PDE4) inhibitor that is being investigated for 
the treatment of atopic dermatitis (AD) and plaque psoriasis (psoriasis).
2.1. Study Rationale 
The purpose of the study is to investigate the efficacy, safety, tolerability and 
pharmacokinetics of topical PF-07038124 in participants with mild to moderate AD or mild 
to moderate psoriasis.  Participants will receive either PF-07038124 or a vehicle control for 
6 weeks.
2.2. Background 
2.2.1. Role of Proinflammatory Cytokines in AD and Psoriasis
ATOPIC DERMATITIS: Atopic dermatitis (AD), also known as atopic eczema, is a
common, chronic, inflammatory skin disorder characterized by flaky skin lesions, intense 
pruritus, and a general deterioration in quality of life.  AD can affect any age group.  
Prevalence estimates suggest approximately 10% of adults and 10%-20% of children suffer 
from AD, and up to 18% of those affected with AD suffer with severe disease.  
There are a limited number of treatments available for AD.  Current treatments for AD 
include emollients, topical corticosteroids (eg, betamethasone, clobetasol, fluocinonide), 
topical calcineurin inhibitors (eg, pimecrolimus, tacrolimus), and coal tar preparations.  
Crisaborole ointment, 2% (weight by weight) (20 mg/g), a PDE4 inhibitor, is approved in the 
United States (US; Eucrisa®) as a topical treatment therapy in patients 3 months of age and 
older with mild to moderate AD; and in Canada (Eucrisa®), Israel, the European Union (EU), 
Australia and China (Staquis®) as a topical treatment therapy in patients 2 years of age and 
older with mild to moderate AD. Additional treatments generally reserved for severe AD 
include phototherapy (eg, ultraviolet A [UVA] light with or without psoralen) and systemic 
agents (eg, corticosteroids, cyclosporine, recombinant IFN-γ, mycophenolate mofetil, 
methotrexate).  None of the currently available therapies offer a cure; therefore, the main 
aims of existing treatments are to reduce the occurrence of acute flares, increase the time 
between relapses, reduce pruritus and reduce the resulting sleep disturbances.
For most AD patients not responding to topical therapies and phototherapy, off-label use of 
systemic agents, which includes both oral corticosteroids and oral immunosuppressants 
remain the last viable treatment option.  Dupilumab injection, an interleukin (IL)-4 receptor
alpha antagonist, was approved for use in patients with moderate to severe AD.  Systemic 
therapy options are associated with potentially severe adverse effects and require careful 
monitoring.  Therefore, the prominent unmet medical need in AD is for an effective, safe 
topical agent for once a day dosing without restrictions on long-term or continuous use, and 
without local or systemic side effects.
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The T-helper-2 response contribute to AD-associated skin inflammation and itch.1 The 
pathogenic role that the T-helper 2 cells (Th2) derived cytokines, IL-4 and IL-13, play in AD 
has been demonstrated through the clinical efficacy of dupilumab, an antibody to the IL-4 
receptor that blocks the activity of both IL-4 and IL-13.2
PSORIASIS: The most common variant of psoriasis, plaque psoriasis (psoriasis vulgaris), is 
a chronic inflammatory skin disease characterized by red, scaly, raised plaques.  Chronic 
plaque psoriasis is a common skin disorder with a worldwide prevalence of 2%. Although 
psoriasis primarily affects the skin and is not a life-threatening disease, it can profoundly 
impact the patient’s quality of life (QoL) resulting in an impairment akin to other major 
diseases, such as type 2 diabetes, myocardial infarction, and arthritis. Current treatments for 
psoriasis include topicals, phototherapy, systemic non-biological therapies (methotrexate,
cyclosporin, acitretin, apremilast [Otezla®]) and biologics.
Proinflammatory cytokines such as tumor necrosis factor (TNF) α, interferon (IFN) γ and 
IL-23/T-helper-17 response cytokines play an important role in the pathogenesis of 
psoriasis.3 Several biologics monoclonal antibodies that target these proinflammatory 
cytokines have been shown to be effective for the treatment of psoriasis in clinical trials.4
Biologic agents used in the treatment of psoriasis include multiple anti-TNF agents (such as 
infliximab, adalimumab, etanercept), anti-IL-12/IL-23 antibodies and anti-IL-17 antibodies.
PDE4 inhibitors such as apremilast (Otezla®) may reduce production of pro‐inflammatory
TNF-α and IFN-γ by increasing cyclic adenosine monophosphate (cAMP) levels.
2.2.2. Description of Investigational Product: Mechanism of Action
Phosphodiesterases (PDE) are a family of enzymes that breakdown the ubiquitous second 
messengers, cAMP and cyclic guanosine monophosphate (cGMP), that regulate various 
cellular processes.  PDE4 is a subfamily that includes the four isozymes, each encoded by 
separate genes, PDE4 A, B, C and D.  Inhibitors of the PDE4 family have been the focus of 
intense drug development over many years due to their broad potential in inflammatory 
diseases such as AD and psoriasis.  For example, apremilast (Otezla®) is an oral 
small-molecule inhibitor of PDE4 that is approved for the treatment of patients with 
moderate to severe plaque psoriasis and active psoriatic arthritis. Crisaborole (Eucrisa®,
Staquis®) is a topically delivered PDE4 inhibitor that has demonstrated efficacy in clinical 
trials5 and is approved for the treatment of mild to moderate AD as described previously. In 
addition, other topical PDE4 inhibitors, such as roflumilast (ARQ-151), have shown activity 
in the treatment of psoriasis.6
PF-07038124 is designed to be a best-in-class, oxaborole-based potent PDE4 inhibitor that 
has increased immunomodulatory activity in T-cell based assays, which correlates with 
inhibition of additional PDE family members that are active in immune cells.  This enhanced 
activity contributes to greater inhibition of cytokines IL-13 and IL-4 from activated T cells 
which may lead to increased clinical activity. 
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PF-07038124 is a potent and selective PDE4 inhibitor intended to be used for topical 
administration for the treatment of AD and psoriasis.  
 
 
PF-07038124 inhibits cytokine production and release from T cells and monocytes in 
peripheral blood mononuclear cells (PBMC) over a range of concentrations that is dependent 
on the cytokine that is being modulated. 
 
 
 
 PF-07038124 increased 
the level of cAMP in human PBMCs in a dose dependent manner, consistent with its primary 
mechanism of action as a PDE inhibitor.  
An ex vivo human skin model of Th2 inflammation was used to measure the activity of 
PF-07038124 in its ointment formulation with topical application.  This model has been used 
to test the activity of other topical therapeutic compounds, including topical corticosteroids, 
Janus kinase (JAK) inhibitors and the PDE4 inhibitor crisaborole (Eucrisa®). 
 
 
 
 
 
 
2.2.3. Preclinical Safety Data 
In the pivotal 3-month toxicity studies in rats (oral) and minipigs (dermal), the systemic 
no-observed-adverse-effect levels (NOAEL) were identified as 4 mg/kg/day and 
0.0104 mg/cm2/day (0.0052 mg/cm2, BID), respectively, with systemic exposures of 2x and 
1.2x, respectively, the projected maximum human exposure (uCav = 9 pg/mL). The systemic 
NOAEL exposure identified in the more sensitive nonclinical species (minipig) was 
11 pg/mL (Cav, unbound).  The local (dermal) NOAEL was identified at the 
0.03% concentration (BID) corresponding to 0.0052 mg/cm2/day (0.0026 mg/cm2, BID) and 
represents an 17x multiple to the projected maximum human dermal dose of 
0.0003 mg/cm2/day in the current study. Based on the completed nonclinical studies, local 
(skin) and systemic (cardiovascular, nervous, and gastrointestinal) target organs/systems 
were identified.  Local reactions (erythema, edema) were observed in minipigs at
≥0.00174 mg/cm2/day (5.8x the highest planned clinical dermal dose, 0.0003 mg/cm2/day).  
A potential for skin sensitization by PF-07038124 was identified in a mouse local lymph 
node assay with a No Observed Effect Level (NOEL) of 0.015 mg/cm2/day (50x the highest 
planned clinical dermal dose, 0.0003 mg/cm2/day).  Cardiovascular effects included increases 
in heart rate, contractility, and/or blood pressure in rats and/or dogs, and vascular 
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injury/compromise (in mesentery, kidney, adrenal gland, and/or bladder) in rats and/or 
minipigs.  Clinical signs indicative of nervous system effects (eg, ataxia, decreased activity, 
hunched posture, twitching, and/or tremors) and gastrointestinal effects (emesis, salivation, 
and/or soft/liquid feces) were also observed in rats, dogs, and/or minipigs, mostly at 
non-tolerated doses.  These systemic effects in nonclinical species are consistent with those 
reported for oral selective PDE4 inhibitors.  PF-07038124 was negative for mutagenicity, 
positive in an in vitro micronucleus assay at high concentrations via aneugenic mechanism, 
but negative in an in vivo rat micronucleus assessment.  PF-07038124 was not phototoxic 
and no further photosafety testing is recommended.  Rat and rabbit embryo-fetal 
development (EFD) was assessed after oral administration of PF-07038124 to pregnant 
animals.  PF-07038124 did not cause any effects on embryo-fetal development following oral 
administration at doses up to 4 mg/kg/day (rats) and 8 mg/kg/day (rabbits), respectively.  The 
developmental NOAEL exposures in pregnant rats and rabbits corresponded to 1.7x and 
2.7x the maximum planned clinical exposure on an unbound Cav (uCav) basis. In addition, no 
effects on fertility were observed in female rats after oral administration of PF-07038124 up 
to 4 mg/kg/day (4.1x the maximum planned dose on an uCav comparison basis).
The nonclinical safety profile of PF-07038124 has been adequately characterized to support 
progression into clinical trials of up to 3 months.
In summary, the nonclinical studies adequately support the planned clinical trials with 
PF-07038124.
 
  
 
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2.3. Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-07038124 may be found in the investigator’s brochure (IB), which is the 
SRSD for this study.
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention PF-07038124
Adverse Nonclinical findings – PDE4 inhibitor 
associated vasculitis
Vasculitis is an effect associated with 
administration of oral PDE4 inhibitors in 
nonclinical species, correlates with an acute 
phase reaction, and occurs at doses above the 
NOAEL and also systemic exposures at the 
clinical Maximum Recommended Human Dose 
(MRHD) for oral PDE4 inhibitors.
Participants will be assessed for safety at regular 
intervals throughout the study (including monitoring 
of acute-phase reactants such as fibrinogen and 
C-reactive protein), systemic exposure will also be 
assessed.
Adverse Nonclinical findings – PDE4-related 
nervous system and gastrointestinal effect (a class 
effect of AEs observed with PDE4 inhibitors)
Clinical signs indicative of nervous system 
effects (eg, ataxia, decreased activity, hunched 
posture, twitching, and/or tremors) and 
gastrointestinal effects (emesis, salivation, and/or 
soft/liquid feces) were observed in rats, dogs, 
and/or minipigs, at non-tolerated doses.
Participants will be assessed for safety at regular 
intervals throughout the study.
Adverse Nonclinical findings – Potential Skin 
Sensitization
The potential for skin sensitization was identified 
as a risk in nonclinical species at dermal 
concentrations 50x above the planned dose 
concentration of 0.01%, with a no observed 
effect level of 0.06% ointment.
Participants will be assessed for safety at regular 
intervals throughout the study, including assessment 
of the administration site. Participants with any 
history of angioedema or anaphylaxis to topical 
products or known sensitivity to any of the 
components of the investigational products will be 
excluded from the study.
Use of a placebo arm 
Participants on placebo may experience a 
worsening of disease.
Participants will be assessed for safety at regular 
intervals throughout the study.  AD and psoriasis are
not life-threatening diseases.
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2.3.2. Benefit Assessment
Based on its cytokine inhibition profile, topical administration of PF-07038124 is anticipated 
to provide potential therapeutic benefit in the treatment of AD by targeting the signaling of 
cytokines in T-helper-2 response and in the treatment of psoriasis by targeting TNF-α. Other 
PDE4 inhibitors, such as crisaborole (Eucrisa®, Staquis®), apremilast (Otezla®), and
roflumilast (ARQ-151)6 have demonstrated efficacy in the treatment of AD or psoriasis.
Based on the clinical data for these PDE4 inhibitors, participants in this study may receive a 
beneficial effect, in addition to regular intensive clinical trial assessment to support 
participants’ management of AD or psoriasis.
The included vehicle has important emollient properties. Some vehicle excipients have a 
more pronounced beneficial effect on the skin and can improve clinical appearance and skin 
barrier function. In particular, white petrolatum, the primary excipient and base of 
PF-07038124 ointment, 0.01%, was selected for its emollient properties and favorable 
tolerability profile. The use of topical emollients is an essential element of AD and psoriasis
treatment and is recommended by published guidelines.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to participants in this study, the potential 
risks identified in association with PF-07038124 are justified by the anticipated benefits that 
may be afforded to participants with AD or psoriasis.
The Benefit/Risk balance of PF-07038124 in Study C3941002 is considered favorable and 
supported by:
•
The satisfactory safety and local tolerability profile on PF-07038124 to date based on 
non-clinical studies 
•
The expected efficacy of PF-07038124 for the treatment of AD and psoriasis based 
on pre-clinical data generated with PF-07038124 as well as the efficacy of other 
approved topical PDE4 inhibitors for the treatment of mild to moderate AD 
(Eucrisa®/Staquis®) and oral PDE4 inhibitors for the treatment of moderate to severe 
psoriasis (Otezla®).
Participants will be monitored closely during the study for safety and local tolerability 
adverse events by the study investigators and sponsor to ensure participant safety.
In conclusion, Pfizer considers that the clinical experience to date with PF-07038124 support 
the continued development of PF-07038124 for the treatment of AD and psoriasis supporting
the initiation of Phase 2a study C3941002. Additional background information on 
PF-07038124 can be found in the current version of the IB, especially the Summary of Data 
and Guidance for the Investigator (Section 7 of the IB).
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Atopic Dermatitis
ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
Primary Objective 
Primary Endpoint
Primary Estimands 
•
To compare the efficacy of 
PF-07038124 versus 
vehicle on percent change 
from baseline in Eczema 
Area and Severity Index 
(EASI) in participants with 
mild or moderate atopic 
dermatitis (AD).
•
Percent change from baseline in 
EASI total score at Week 6.
•
Estimand E1: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the
investigational product (IP)
on a continuous endpoint; 
without the benefit of 
additional prohibited 
medications during 
treatment and regardless of 
participant compliance with 
the IP dosing.
Secondary Objectives: 
Secondary Endpoints
Secondary Estimands 
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using Investigator’s Global 
Assessment (IGA) score 
assessment as endpoint in 
participants with mild or 
moderate AD.
•
Proportion of participants 
achieving IGA score of clear (0) 
or almost clear (1) (on a 5-point 
scale) and a reduction from 
baseline of ≥2 points at Week 6.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications and regardless of 
a participant compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of disease 
severity and symptoms as 
endpoints in participants 
with mild or moderate AD.
•
Proportion of participants 
achieving EASI 75 
(75% improvement from 
baseline) at study visit time 
points specified in the SoA.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications and regardless of 
a participant compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of patient 
reported outcomes (PRO), in 
participants with mild or 
•
Proportion of participants having 
≥4 points of reduction in weekly 
averages of Peak Pruritus 
Numerical Rating Scale 
(PP-NRS) from baseline at study
visit time points specified in the 
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
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ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
moderate AD.
SoA.
of additional prohibited 
medications and regardless of 
a participant compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle, 
on measures of disease and 
symptom severity in
participants with mild or 
moderate AD.
•
Change from baseline in EASI 
total score at study visit time 
points specified in the SoA.
•
Proportion of participants 
achieving IGA score of clear (0) 
or almost clear (1) at study visit 
time points specified in the SoA.
•
Percent change from baseline in 
affected Body Surface Area 
(BSA) at study visit time points 
specified in the SoA.
•
All continuous secondary 
endpoints will be analyzed 
descriptively and using 
estimand E1 described above, 
when appropriate.
•
All categorical secondary 
endpoints will be analyzed 
descriptively and using 
estimand E2 described above, 
when appropriate.
•
To characterize the safety 
and tolerability of 
PF-07038124 versus vehicle 
in participants with mild or 
moderate AD.  
• Incidence of treatment emergent 
adverse events (AEs) and serious 
adverse events (SAEs), clinically 
significant changes in vital signs, 
electrocardiogram (ECG), and 
laboratory tests.
•
Incidence of severity grades in 
skin tolerability at times indicated 
in SoA.
•
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
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3.2. Psoriasis
PSORIASIS
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on change from baseline in 
Psoriasis Area and Severity 
Index (PASI) score in 
participants with mild to 
moderate plaque psoriasis. 
•
Change from baseline in PASI 
score at Week 6.
•
Estimand E1: This estimand is 
intended to provide a 
population level estimate of 
the treatment effect of the 
investigational product (IP) 
alone on a continuous 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
Secondary: 
Secondary: 
Secondary:
•
To compare the efficacy of 
PF-07038124 versus vehicle
on Physician Global
Assessment (PGA) score in 
participants with mild to 
moderate plaque psoriasis.
•
Proportion of participants with 
PGA score clear (0) or almost 
clear (1) (on a 5-point scale)
and ≥2 points improvement 
from baseline at Week 6. 
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
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PSORIASIS
Objectives
Endpoints
Estimands
participants compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on the proportion of 
participants with mild to 
moderate plaque psoriasis 
achieving PASI 75. 
•
Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from 
baseline) at study visit time 
points specified in the SoA.
•
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus 
vehicle, using measures of 
patient reported outcomes 
(PRO), in participants with 
mild or moderate plaque 
psoriasis.
•
Proportion of participants who
achieved a Psoriasis Symptoms 
Inventory (PSI) score of 0 (not 
at all) or 1 (mild) on every item 
at study visit time points 
specified in the SoA.
•
Estimand E2: This estimand is 
intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
•
To compare the efficacy of 
PF-07038124 versus vehicle 
on measures of disease and 
symptom severity in 
participants with mild to 
moderate plaque psoriasis. 
•
Change from baseline in PASI 
scores at study visit time points 
specified in the SoA (except 
Week 6). 
•
Percent change from baseline in 
PASI scores at study visit time 
points specified in the SoA. 
•
Proportion of participants with 
PGA score clear (0) or almost 
clear (1) and ≥2 points 
improvement from baseline at 
time points specified in the
SoA.
•
Percent change from baseline in 
BSA at study visit time points 
specified in the SoA.
•
All other continuous 
secondary endpoints will be
analyzed descriptively and 
using estimand E1 described 
above when appropriate.
•
All other categorical 
secondary endpoints will be 
analyzed descriptively and 
using estimand E2 described 
above when appropriate.
•
To assess safety and 
tolerability of PF-07038124
in participants with mild to 
moderate plaque psoriasis.
•
Incidence of treatment emergent 
adverse events (AEs) and 
serious adverse events (SAEs), 
clinically significant changes in 
vital signs, electrocardiogram 
(ECG), and laboratory tests.
•
Incidence of severity grades in 
•
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
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PSORIASIS
Objectives
Endpoints
Estimands
skin tolerability at times 
indicated in SoA.
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4. STUDY DESIGN
4.1. Overall Design
This is a phase 2a, randomized, double blind, vehicle controlled, parallel group, multicenter 
study on the efficacy, safety, tolerability and PK of PF-07038124 0.01% QD versus vehicle 
control in the treatment of adult participants with mild to moderate AD or mild to moderate 
plaque psoriasis.  In this study the efficacy of PF-07038124 ointment versus vehicle will be 
assessed in two different indications – there is a separate vehicle control group for each 
indication.
A total of approximately 88 participants with AD or psoriasis will be randomly assigned to 
study intervention in this basket trial design.
For AD, a maximum of approximately 56 participants will be randomly assigned to study 
intervention such that approximately 42 evaluable participants complete the study.
Assuming a 25% drop out rate, approximately 28 participants will be randomized to either 
PF-07038124 or vehicle control to achieve approximately 21 completers in each group.
Randomization will be stratified by baseline disease severity (mild [Investigator's Global 
Assessment or IGA = 2] vs. moderate [IGA = 3]). Up to 25% of AD participants will have 
an IGA score of 2 at baseline. 
For psoriasis, a maximum of approximately 32 participants will be randomly assigned to 
study intervention such that approximately 24 evaluable participants complete the study.  
Assuming a 25% drop out rate, approximately 16 participants will be randomized to 
PF-07038124 or vehicle control to achieve 12 completers in each group. Randomization will
be stratified by baseline disease severity (mild [Physician Global Assessment or PGA = 2]
vs. moderate [PGA = 3]). Up to 25% of participants will have a PGA score of 2 at baseline. 
The total duration of study participation will be approximately 17 weeks, including a 
screening period of up to 6 weeks, a double-blind, placebo-controlled treatment period of
6 weeks, and a safety follow-up period of 4-5 weeks from last dose of study drug to last 
study visit. The study intervention arms and duration for AD and psoriasis participants are 
the same (See Section 1.1 for detailed Study Intervention Groups and Section 1.2 for Study 
Schema).
4.2. Scientific Rationale for Study Design
This 6-week study is the first time a topical PF-07038124 ointment is being evaluated in the
AD and psoriasis populations.  Previous Pfizer trials in these indications indicate that a 
6-week duration is appropriate to assess the efficacy, safety and tolerability.  The current 
nonclinical toxicology package supports the study durations of up to 12 weeks.
For AD the primary endpoint is percent change from baseline in Eczema Area and Severity 
Index (EASI); secondary endpoints include Investigator’s Global Assessment (IGA).
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For psoriasis the primary endpoint is percent change from baseline in Psoriasis Area and 
Severity Index (PASI); the secondary endpoints include Physician Global Assessment 
(PGA).
Human reproductive safety data are limited for PF-07038124, but there is no suspicion of 
human teratogenicity based on the intended pharmacology of the compound.  In addition, 
EFD studies conducted in pregnant rats and rabbits at exposures that correspond to 1.7x and 
2.7x the maximum planned clinical exposure did not cause any effects on embryo-fetal 
development.  See Appendix 4 for contraceptive requirements.
4.2.1. Participant Input into Design
Not applicable.
4.3. Justification for Dose
The nonclinical safety profile of PF-07038124 following systemic administration to rats and 
topical application to minipigs supports human clinical studies of up to 3 months in duration
(See Section 2.2). The dose proposed for this study was determined considering all relevant 
information obtained from nonclinical safety studies, incorporating the NOAEL from 
3-month studies in minipigs, together with the systemic exposure observed following topical 
application of PF-07038124 to healthy participants. As a result, the dose strength of 
PF-07038124 selected for this study is 0.01%, applied once daily. 
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4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit shown in the SoA.
The end of the study is defined as the date of the last visit of the last participant in the study 
in the trial globally.
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
The inclusion criteria for AD and psoriasis are overlapping but different. Details of the 
overlapping inclusion criteria are provided in Section 5.1.1; Disease-specific inclusion 
criteria are provided in Section 5.1.2.1 and Section 5.1.2.2 for AD and psoriasis respectively.
Participants are eligible to be included in the study only if all of the following criteria apply:
5.1.1. General Inclusion Criteria Applicable for both AD and psoriasis
1. Male or female participants between the ages of 18 and 70 years, inclusive, at Visit 1
(Screening Visit/time of informed consent).
•
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
2. Body weight ≥50 kg and Body Mass Index (BMI) ≥17.5 kg/m2 up to 40 kg/m2
(inclusive).
3. 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.
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures. Refer to 
Section 5.3 for Lifestyle considerations.
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5.1.2. Disease-Specific Inclusion Criteria 
5.1.2.1. AD Specific Inclusion Criteria
1. Have been diagnosed with AD for at least 3 months prior to Day 1; the clinical 
diagnosis of AD will be confirmed according to the criteria of Hanifin and Rajka7
(Appendix 11).
2. Have an Investigator’s Global Assessment (IGA) score of 2 (mild), or 3 (moderate) at 
both the Screening and Day 1/Randomization. Note: Refer to Section 8.1.2.2 for the
assessment of 5-point IGA.
3. Have AD covering 5% to 20% (inclusive) of BSA (excluding the scalp) at both the 
Screening and Day 1/Randomization.  Note: Refer to Section 8.1.2.3 for detailed 
methods of calculating treatable BSA.
4. Have an EASI total score of ≥3 to ≤21 at Screening and at Day 1/Randomization.
Note: Refer to Section 8.1.2.1 for method of calculating EASI scores.
5. Have a Baseline Peak Pruritis Numerical Rating Scale (PP-NRS) average score of 
≥2 assessed at Day 1/Randomization.
5.1.2.2. Psoriasis Specific Inclusion Criteria
1. Participants with a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 
6 months prior to Day 1.
2. Participants with a Physician Global Assessment (PGA) score of 2 (mild), or 
3 (moderate) at Screening and Day 1. Note: Refer to Section 8.1.4.2 for the 
assessment of 5-point PGA.
3. Having plaque psoriasis covering 5% to 15% (inclusive) of BSA (excluding the scalp)
at both the Screening and Day 1/Randomization.  Note: Refer to Section 8.1.4.3 for 
detailed methods of calculating treatable BSA.
5.2. Exclusion Criteria
The exclusion criteria for AD and psoriasis are the same.
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Presence of skin comorbidities that would interfere with study assessment or response 
to treatment.
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2. Any psychiatric condition including recent or active suicidal ideation or behavior that 
meets any of the following criteria at Screening or Day 1: 
a.
Suicidal ideation associated with actual intent and/or plan in the past year: “Yes” 
answers on items 4 “some intent to act without specific plan” or 5 “specific plan 
and intent” of the Columbia Suicide Severity Rating Scale (C-SSRS);
b. 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;
c.
Any lifetime history of serious or recurrent suicidal behavior;
d. The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria;
e.
In the opinion of the investigator or Pfizer (or designee) exclusion is required.
3. Current or recent history (within approximately 3 months prior to Day 1) of severe, 
progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, 
endocrine, pulmonary, cardiovascular, or neurological disease.
4. A history of systemic (within approximately 3 months prior to Day 1), chronic or 
acute skin infection (within approximately 2 weeks prior to Day 1) requiring 
hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically 
significant by the investigator.
5. A known immunodeficiency disorder or a first degree relative with a hereditary 
immunodeficiency.
6. Undergone significant trauma or major surgery within 1 month prior to screening.
7. Have a history of cancer within 5 years or has undergone treatment for any type of 
cancer, with the exception of adequately treated or excised non-metastatic basal cell 
or squamous cell cancer of the skin or cervical carcinoma in situ with no evidence of 
recurrence.
8. Have a history of angioedema or anaphylaxis to topical products or known sensitivity 
to any of the components of the investigational products.
9. 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 judgment, make the participant 
inappropriate for the study.
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Prior/Concomitant Therapy:
10. Has received any of the prohibited medications/therapies that may alter the course of 
the diseases under study without the required minimum washout period or anticipated 
concomitant use of any of the prohibited medications/therapy (see Appendix 10).
Prior/Concurrent Clinical Study Experience:
11. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of study intervention
used in this study (whichever is longer). 
Note: Any investigational or experimental therapy taken or procedure performed for 
AD, psoriasis, psoriatic arthritis or rheumatoid arthritis in the previous 1 year should 
be discussed with the Pfizer Medical Monitor (or designee).  Participants cannot
participate in studies of other investigational or experimental therapies or procedures 
at any time during their participation in this study.
Diagnostic Assessments:
12. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, QTc interval >450 msec, 
complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST-T
interval changes suggestive of myocardial ischemia, second or third degree AV block, 
or serious bradyarrhythmias or tachyarrhythmias).  If the baseline uncorrected QT 
interval is >450 msec, this interval should be rate-corrected using the Fridericia 
method and the resulting QTcF should be used for decision making and reporting.  If 
QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 
2 more times and the average of the 3 QTc or QRS values should be used to 
determine the participant’s eligibility.  Computer-interpreted ECGs should be 
overread by a physician experienced in reading ECGs before excluding participants.
13. Participants with ANY of the following abnormalities in clinical laboratory tests at 
Screening, as assessed by the study specific laboratory and confirmed by a single 
repeat (the last value will be used to determine eligibility), if deemed necessary: 
a.
Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2;
b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values 
≥2 times the ULN; 
c.
Total bilirubin ≥1.5 times the ULN; participants with a history of Gilbert's 
syndrome may have a direct bilirubin measured and would be eligible for this 
study provided the direct bilirubin is ≤ULN.
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14. In the opinion of the investigator or sponsor, have any uncontrolled clinically 
significant laboratory abnormality that would affect interpretation of study data or the 
participant’s participation in the study.
Other Exclusions:
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.
16. A history of alcohol or substance abuse within 6 months prior to Screening that in the 
opinion of the investigator will preclude participation in the study.
17. In the opinion of the investigator or Sponsor Clinician or Sponsor Medical Monitor, 
the participant is inappropriate for entry into this study.
5.3. Lifestyle Considerations
5.3.1. 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 and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 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 acceptable 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 permitted methods of contraception).  In addition, the investigator or designee will 
instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant or partner.
5.3.2. Dietary Supplements
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.  Vitamins, minerals 
and purified food substances are allowed in amounts not known to be associated with adverse 
effects (such as hypervitaminosis). Herbals supplements are only allowed on a case by case 
basis; please contact the Pfizer staff.  Herbals eg, St. John’s Wort that are known to have an 
effect on drug metabolism must be discontinued at least 4 weeks or 5 half-lives (whichever is 
longer) before Day 1. 
5.3.3. Medications/Treatments Discontinuation, Non-Medicated Emollients
Participants are required to discontinue and avoid using certain medications and treatments as 
described in Section 10.10 Appendix 10. Prohibited Prior and Concomitant Medications
including medications which may result in Drug-Drug Interaction (DDI).  
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All topical medications and treatments that could affect atopic dermatitis and psoriasis skin 
areas must be discontinued for the duration of the study, if the skin areas are to be treated 
with IP.  
Unless specified in Appendix 10, any other concomitant medication for AD or psoriasis will 
be considered on a case by case basis by the investigator in consultation with the Sponsor 
Medical Monitor.
Non-medicated emollient and sunscreen are the only topical products permitted to be used on 
AD and psoriasis skin during the Screening period. Participants will stop applying 
non-medicated emollient and sunscreen on atopic dermatitis/psoriatic skin 24 hours prior to 
Day 1/Randomization.  During the study treatment period, use of non-medicated emollient 
and sunscreen are allowed only on skin that was considered normal or non-lesional at Day 1 
(ie, never treated with IP).  Any non-medicated emollient used by the participant during the 
study should be documented in study records and the Case Report Form (CRF). 
Low or least potent (Class 6 or 7) topical corticosteroids (Hydrocortisone ≤1% and 
hydrocortisone acetate ≤1%) are the only topical corticosteroids permitted for the treatment 
of areas never treated with IP (eg, palms, soles, face, and intertriginous).  Scalp tar 
preparations, salicylic acid preparations and shampoos free of corticosteroids are permitted 
for the treatment of scalp.  
Due to the potential to affect atopic dermatitis and psoriasis with ultraviolet light exposure, 
participants must avoid prolonged exposure to the sun and avoid the use of tanning booths, 
sun lamps or other ultraviolet light sources during the study. Please see Appendix 10 for 
details on prohibited light therapy.
5.3.4. Other Lifestyle Requirements
•
Participants should not apply occlusive dressing(s) to the areas treated with IP. 
•
Participants should not swim, bathe, be bathed or have treatment areas washed for at 
least 4 hours after application of the IP. 
•
Use of sunscreen and regular moisturizes is permitted, but only on areas which are 
not treated with IP. 
•
The participant should avoid wiping the IP off the skin and the IP should not be 
re-applied to areas that were inadvertently wiped until the next scheduled dose.
•
Participants will agree to avoid strenuous exercise during the study, especially within 
48 hours prior to the scheduled study visits and maintain adequate hydration, if 
possible.
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•
On study visit days, the participants will not smoke or use nicotine-containing 
products, or ingest caffeine (eg, tea, coffee, some soft drinks/colas/energy drinks and 
power bars) during the 2 hours prior to blood pressure and pulse (heart) rate 
measurements.
•
On study visit days, showering or bathing is permitted prior to attending the study 
visit, but moisturizing will not be done. 
•
On study visit days, prescribed permitted concomitant medication will be taken, as 
needed, prior to the study visit, if it can be administered with water only.
•
The participants will contact the study site investigator if there are any changes or 
additions to concomitant medications.
•
The participants will avoid having major elective surgery until after the final study 
assessments.
•
The participants should continue all non-pharmacological therapies, such as physical 
therapy, as indicated.  However, the participants should avoid changing the type or 
intensity of therapy or initiating new therapy until after Week 6 visit.
•
When applying the IP, the participant will not be required to wear gloves.  However, 
participants should be instructed to wash their hands with mild soap and water before 
and after each application. 
•
If study participants need someone else to assist with applying investigational product 
on hard to reach areas (eg back), this person must wear gloves to avoid accidental 
exposure to the IP. 
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants to 
meet the 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 
re-screened once if they fail the screening evaluation for reasons related to incidental 
transitory conditions, unless the reason for the screen failure is the disease severity inclusion 
criteria. Participants may not be rescreened unless approved by the sponsor. Rescreened 
participants should be assigned a new participant number.
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6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to PF-07038124 0.01% ointment 
and PF-07038124 vehicle ointment (placebo).
6.1. Study Intervention Administered
Intervention Name
PF-07038124 0.01% ointment
PF-07038124 vehicle ointment
ARM Name
(group of patients receiving a 
specific treatment (or no treatment)
Participants with mild or 
moderate AD, or mild or 
moderate psoriasis
Participants with mild or 
moderate AD, or mild or 
moderate psoriasis
Type
Drug
Drug
Dose Formulation
Ointment
Ointment
Unit Dose Strength(s)
0.1 mg/g ointment in 60-gram 
tube
0 mg/g ointment in 60-gram 
tube
Dosage Level(s)
0.01% (wt/wt), QD
0% (wt/wt), QD
Route of Administration
Topical
Topical
Use
Experimental
Placebo
IMP or NIMP
IMP
IMP
Sourcing
Provided centrally by the 
sponsor.
Provided centrally by the 
sponsor.
Packaging and Labeling
Study intervention will be 
provided in cartons.  Each carton 
will contain one tube.  Both the 
carton and tube will be labeled 
in a blinded format as required 
per country requirement.
Study intervention will be 
provided in cartons.  Each 
carton will contain one tube.  
Both the carton and tube will 
be labeled in a blinded format 
as required per country 
requirement.
6.1.1. Administration
6.1.1.1. Treatable Areas
AD treatable areas will be all areas affected by AD, except scalp.
Psoriasis treatable areas will be all areas affected by psoriasis, except scalp and nails.
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A thin layer of IP ointment will be applied at a target application rate of approximately 
3 mg/cm2 by using a fingertip unit (FTU) method.
Day 1 Visit
At the Day 1 Visit, before the Day 1 initial IP application is performed, the designated areas 
for treatment will be identified and documented in the participant’s source document study 
records (body map). The participant and/or caregiver will be provided with a paper version of 
the body map. 
On Day 1 through the final dose at Week 6 visit, the IP should be applied once daily (around 
same time of the day), to all treatable AD or psoriasis involved areas identified at the Day 1 
visit. 
All participants will be supplied with instructions on application and dose frequency 
commensurate to assigned treatment arm. Those participants having difficulty reaching 
treatment-eligible areas (eg, back) may be assisted by another person who will need to apply 
the IP to the participant according to the investigational product application instructions. The 
person assisting with the application must wear gloves to avoid any exposure to the IP. 
Participants and/or caregivers will be encouraged to observe and participate in the initial IP 
application on Day 1. 
Post Day 1 Visits
After Day 1/Randomization, all subsequent doses will be applied at home except the dose on 
the days of in-clinic visits. 
 
 The last dose of 
IP will be applied during the Week 6 in-clinic visit (EOT visit) as specified in Section 1.3.3
of the SoA.
The participant and/or caregiver will be instructed to complete the Dosing Diary starting with 
the first dose applied in the clinic on Day 1 through Week 6 (each time IP is applied) for all 
IP doses applied. If a participant misses applying a dose, the participant should apply this 
dose provided this dose should have been applied within the last 6 hours. For longer 
intervals, the dose should be skipped. The missed dose should be recorded in the dosing 
diary. The next dose should be applied according to the regular dosing regimen.
Treated area identified on Day 1 should be continued to be treated even if substantial 
improvement or clearing of AD or psoriasis occurs. The reason for maintaining IP treatment 
areas the same as identified at Day 1 is to understand the efficacy, systemic safety, and local 
tolerability of PF-07038124 ointment when applied to for 6 weeks in participants with mild 
or moderate AD or psoriasis.
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Post Day 1, any new AD or psoriasis on treatment-eligible areas identified by the participant 
or caregiver(s) should also be treated with the IP. Decision to apply the IP to new eligible 
areas should be made following assessment by the Investigator or his/her designee. An 
unscheduled visit for assessment of the new lesion may be required at the discretion of the 
investigator. Body map will be updated, and IP need will be re-assessed at every site visit 
during the treatment period. If the total, treatable BSA exceeds 20% (AD) or 15% (psoriasis) 
during the six-week treatment period, the participant will still remain eligible for the study, 
given that the total, treatable BSA does not exceed 22% (for AD) or 16.5% (for psoriasis). If 
the total, treatable BSA exceeds 22% (AD) or 16.5% (psoriasis), the Sponsor may decide to 
discontinue the participant.
Participants and/or caregivers will be instructed not to wipe investigational product off the 
skin, avoid applying an occlusive dressing to the treated areas, and refrain from swimming or 
bathing/washing the treated areas within 4 hours after application.
Under no circumstances will the investigational drug application regimen be modified 
(eg, frequency of application increased or reduced, not stopped, or the application rate [target 
3 mg/cm2] increased or reduced) during the study. Temporary discontinuation of 
investigational drug may be appropriate under some circumstances (eg, surgery, non-serious 
infections) and should be discussed with the Medical Monitor (or designee) preferably prior 
to temporary discontinuation of investigational drug.
Study intervention administration details will be recorded on the CRF.
6.2. Preparation/Handling/Storage/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 
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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 
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
Within this protocol, preparation refers to the investigator site activities performed to make 
the IP ready for application or dispensing to the participant/caregiver by qualified staff.
Dispensing is defined as the provision of IP, concomitant treatments, and accompanying 
information by qualified staff member(s) to a healthcare provider, participant, or caregiver in 
accordance with this protocol. Local health authority regulations or investigator site 
guidelines may use alternative terms for these activities.
The IP will be dispensed in a blinded fashion using an interactive response technology (IRT) 
system at Day 1/Baseline, Week 1, Week 2 and Week 4 visits. A qualified staff member will 
dispense the IP via unique container numbers on the cartons provided, in quantities 
appropriate for the study visit schedule and the treatable % BSA.
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For doses to be applied at home, the participant or caregiver should be instructed to maintain 
the product in its original package provided throughout the course of dosing and return the 
product and its original package (including empty, partial used and unused tubes) to the site 
at the next study visit. 
IP will be assigned to participants at the Day 1 visit once the participant is successfully 
randomized through the IRT system. The investigator, appropriate delegate or site personnel 
will access the IRT system at screening and all subsequent IP dispensing visits to enter 
information including, but not limited to, the participants height, weight and % affected BSA 
to receive correct tube numbers to be dispensed to the participant. Alternatively, the tool to 
standardize the IP need calculation across participants and study sites may be provided by the 
sponsor.
The calculation of treatable BSA is described in Section 8.1.2.3 and Section 8.1.4.3 for AD 
and psoriasis respectively.
All tubes of investigational product dispensed or returned will be recorded and documented.
6.2.2. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the IP supplies. All investigational products will be accounted for using 
a drug accountability form/record. All tubes of the IP must be returned to the investigator by 
the participant at every visit and at the end of the trial.
The participant will be asked to bring all dispensed IP (including empty, partially used and 
unused tubes) at every ‘compliance check’ visit; participants will be asked to bring dosing 
diary to the clinic at every clinic visit. All previously dispensed IP tubes will be retained by 
the site. For each participant, IP tubes with caps will be weighed individually or collectively 
by the study site before dispensing and after return and the weights will be recorded. The 
sponsor will use the recorded weights to estimate usage (eg, mg/cm2/application) for each 
participant. Note that the weight recorded on the IP label is a nominal weight and not an 
exact weight of the IP and tube. Detailed drug accountability records, including tube weights 
measured in the clinic, will be maintained by study staff for each participant.
The original IP accountability log, or equivalent document, must be accurately completed, 
signed by the Investigator, and retained at the study site (with a copy supplied to the 
Sponsor) when the study is complete.
6.2.3. Destruction of Investigational Product Supplies
For all IP returned to the investigator by the participant, the investigator will maintain the 
returned supply until destruction is authorized.
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The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
Further guidance and information for the final disposition of unused study interventions are 
provided in the IP manual.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation of participants to treatment groups will proceed through the use of an IRT system 
(IWR).  The site personnel (study coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and DU or container number when study 
intervention is being supplied via the IRT system.  The IRT system will provide a 
confirmation report containing the participant number, randomization number, and DU or 
container number assigned.  The confirmation report must be stored in the site’s files. 
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be 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.
6.3.2. Breaking the Blind 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
treatment assignment is warranted. Participant safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a
participant’s treatment assignment unless this could delay further management of the 
participant. However, discussion with the Sponsor in advance of unblinding is not required. 
If a participant’s treatment assignment is unblinded, the sponsor must be notified within 
24 hours after breaking the blind. The date and reason that the blind was broken must be 
recorded in the source documentation and CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
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6.4. Study Intervention Compliance
The participant and/or a caregiver will apply IP at home or during in-clinic visits as specified 
in the SoA.  The participant and/or caregiver will be instructed to complete the Dosing Diary 
starting with the first dose applied in the clinic on Day 1 through Week 6 (each time IP is 
applied) for the IP doses applied at home.  Participants will be instructed to refrain from 
dosing at home on the day of the in-clinic visit, and are to bring to the clinic all used, 
partially used and empty IP tubes in their original containers for weighing, at each visit. 
Participant compliance with IP will be assessed on visits identified in the SoA. Compliance 
will be assessed by review of the participant/caregiver completed Dosing Diary and by 
weighing of the returned IP tubes.  The difference in weight(s) of the returned IP tubes will 
be used to estimate the doses applied.  Source documents will be placed in the participant’s 
study file.  Deviation(s) from the prescribed dosage regimen should be recorded in the CRF.
From Day 1 through Week 6 visit, non-compliance is defined as less than 80% or more than 
120% of IP applications.  If non-compliance is identified, or even if a few dose applications 
are missed or over-applied, then, participants will be re-trained on the importance and the 
process of proper IP application.  If non-compliance persists, the investigator, in consultation
with the Sponsor, may withdraw any participant from the study for reasons of 
non-compliance with the dosing regimen.  Investigators should indicate on the appropriate 
CRF page noncompliance with study intervention and provide an explanation. 
Inventory control of all IPs must be rigorously maintained throughout the duration of the 
study until all medication has been accounted for and/or returned to the sponsor.  Any 
discrepancies noted between drug dispensing records and the drug inventory must be 
reported to Pfizer.
6.5. Concomitant Therapy
All prior medications including non-medication therapies, as well as biologic drugs used for 
AD or psoriasis within 180 days prior to Screening will be recorded at the Screening Visit. 
Medications taken during Screening will be documented as prior medications.  Medications 
taken after the first dose of study intervention has been administered will be documented as 
concomitant medications.  All concomitant medications taken during the study must be 
recorded in study records with indication, daily 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 visit.  Any new concomitant medications or dose changes to current 
concomitant medications should be evaluated for potential new or worsening AEs. 
Refer to Appendix 10 for the list of prohibited concomitant medications and the timeframe 
for which they must be stopped.  
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
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Concomitant medications for other stable chronic medical conditions are permitted during 
the study unless the medication/therapy is specifically prohibited by the protocol or is 
expected to affect the study assessments. Nonsteroidal anti-inflammatory drugs are allowed 
throughout the study. 
Routine preventative immunizations are permitted during the study; however, it is preferred 
that immunizations be administered at least 28 days before the start or following the 
completion of the subject’s participation in study. Vaccines used in the event of a disease 
outbreak or pandemic are allowed.
6.5.1. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with PF-07038124; standard medical 
supportive care must be provided to manage the AEs. 
6.6. Dose Modification
Not applicable.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation).  Reasons for definitive discontinuation of study 
intervention include the following: Liver injury, ECG changes, pregnancy, local tolerability, 
and AEs.  
Note that discontinuation of study intervention does not represent withdrawal from the study.  
If study intervention is definitively discontinued, the participant will proceed to ET and 
remain in the study to be evaluated for follow up visits.  See the SoA for data to be collected 
at the time of discontinuation of study intervention and follow-up for any further evaluations 
that need to be completed. The site will inform the Sponsor Medical Monitor or Sponsor 
clinician if the below criteria for permanent discontinuation of the study intervention are 
triggered.
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.
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Liver Injury
Please refer to Section 10.6 Appendix 6 for Potential Cases of Drug-Induced Liver Injury 
(DILI; Hy’s law).
ECG Changes
A participant who meets either bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from the study intervention. 
•
QTcF >500 msec.
•
Change from baseline: QTcF >60 msec.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed.  This review of the ECG printed at the time of collection must be documented.  Any 
new clinically relevant finding should be reported as an AE.
Pregnancy
Pregnancy confirmed by serum β-hCG testing.  Sponsor Clinician or Sponsor Medical 
Monitor should be notified immediately.
Two negative pregnancy tests are required before randomization (1 negative serum 
pregnancy test at screening and 1 negative urine pregnancy test at Day 1 visit).  If urine 
pregnancy test is positive after study intervention application, serum pregnancy test will be 
conducted, study intervention application paused and sponsor clinician and sponsor medical 
monitor notified immediately.
Local Tolerability 
If a participant experiences severity Grade 3 (severe) or 4 (very severe) on the local 
tolerability assessment (Section 8.2.7), study treatment will be discontinued permanently, and 
participant will proceed to ET visit and follow-up as described in SoA. 
If a participant experiences application site reaction of Grade 2 (moderate) on the local 
tolerability assessment, investigator may temporarily discontinue application of IP for up to 
48 hours without consulting the Sponsor.  If in the clinical judgment of the investigator IP
interruption beyond 48 hours is advisable, the investigator must obtain agreement from the 
Pfizer medical monitor to continue withholding IP.  If temporary IP interruption for more 
than 5 consecutive days is needed, then the participant should be permanently withdrawn 
from treatment and should follow-up with the site until complete or near complete resolution 
of the AE.  This dosing gap may occur only once for the same participant.
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AEs
Hypersensitivity Reactions: If signs and symptoms of hypersensitivity are attributable to the 
investigational product, including contact urticaria, it must be discontinued immediately, and 
appropriate therapy initiated. 
7.1.1. Temporary Discontinuation
Temporary discontinuations of IP 
•
Will occur in cases of positive urine pregnancy test which if confirmed by serum 
pregnancy test will lead to permanent discontinuation (Section 7.1). 
•
May apply in some cases application site reaction during local tolerability 
assessments (Section 8.2.7). 
•
Additional instances of temporary discontinuation may be appropriate (eg, surgery, 
infection, etc). 
All temporary discontinuations should be discussed with Sponsor Clinician or Sponsor 
Medical Monitor to determine if participant may continue in the study.  If possible, site will 
consult sponsor prior to temporary discontinuation.
7.1.2. Rechallenge
Not applicable.
7.2. Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:
•
Refused further follow-up;
•
Lost to follow-up;
•
Death;
•
Study terminated by sponsor.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the 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. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study.  Participants should be questioned regarding 
their reason for withdrawal. The participant will be permanently discontinued both from the 
study intervention and from the study at that time.
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If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or posttreatment study follow-up, and entered on the appropriate CRF page.  In the event 
that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
•
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;
•
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;
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•
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.  
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.
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately
185 mL.  The actual collection times of blood sampling may change.  Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 60 consecutive 
days.
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8.1. Efficacy Assessments
8.1.1. Rater Qualifications
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study.  The minimum qualifications a rater must meet for each study 
rating assessment will be outlined in the Rater Assessment Guide provided to each
participating site.  The level of experience with the target population (or equivalent), specific 
scale experience (or equivalent), and certification required (if applicable) will be listed and
used to determine whether a rater is approved for a given assessment.  Proposed raters who 
do not meet specific criteria but who may be qualified based on unique circumstances may be 
individually reviewed by the study clinical team to determine whether or not a waiver may be 
issued.  The rater must become certified to perform selected study assessments before he or 
she can participate in the conduct of the study.  For specifically defined assessments, rater 
training and standardization exercises may be conducted, and written and signed 
documentation will be provided by the site for each rater’s certification.  In return, each site 
will be provided written and signed documentation outlining each rater’s certification for 
specific study assessments.  Recertification may be required at periodic intervals during the 
study.  The raters who administer specific study assessments will be documented in a 
centralized location and all site staff who administer ratings will be verified in the site study 
documentation during the conduct of the study.
EFFICACY ASSESSMENTS FOR AD
All efficacy assessments will be based on areas treated with IP, and excluding scalp, palms 
and soles from the assessment/scoring.
8.1.2. Physician Assessments for AD
8.1.2.1. Eczema Area and Severity Index (EASI)
The EASI quantifies the severity of a participant’s AD based on both severity of lesion by 
clinical signs and the percent of BSA affected.  EASI is a composite scoring 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.8
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 5 below.
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Table 5.
Clinical Sign Severity Scoring Criteria for EASI
Score
Description
Erythema (E)
0
Absent
None; may have residual discoloration (post-inflammatory hyperpigmentation and/or 
hypopigmentation)
1
Mild
Light pink to light red
2
Moderate
Red
3
Severe
Deep, dark red
Induration/Papulation (I)
0
Absent
None
1
Mild
Barely palpable to slight, but definite hard thickened skin and/or papules
2
Moderate
Easily palpable moderate hard thickened skin and/or papules
3
Severe
Severe hard thickened skin and/or papules
Excoriation (Ex)
0
Absent
None
1
Mild
Slight, but definite linear or picked scratch marks or penetrating surface injury
2
Moderate
Moderate linear or picked scratch marks or penetrating surface injury
3
Severe
Severe linear or picked scratch marks or penetrating surface injury
Lichenification (L)
0
Absent
None
1
Mild
Barely perceptible to slight, but definite thickened skin, fine skin markings, and 
lichenoid scale
2
Moderate
Moderate thickened skin, coarse skin markings, and coarse lichenoid scale
3
Severe
Severe thickened skin with very coarse skin markings and lichenoid scale
* The EASI will exclude scalp, palms and soles from the assessment/scoring.
BSA with AD for EASI Assessment (excluding scalp, palms and soles)
BSA affected by AD should be calculated in each of the four body regions, ie, head and neck 
(h), upper extremities (u), trunk (t), and lower extremities (l).  The area within each body 
region with the key signs of the disease is estimated using handprint as a measure, where the 
full palmar hand of the participant (ie, the participant’s fully extended palm, fingers and 
thumb together) represents approximately 1% of the total BSA.
Each region is typically assigned proportionate body surface areas of 10 (h), 20 (u), 30 (t), 
and 40 (l) handprints respectively.  Refer to Table 6 to identify the surface area equivalent of 
1 handprint in each respective body region.
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Table 6.
Handprint Determination of Body Region Surface Area for AD
Body Region
Total Number of Handprints 
in Body Region
Surface Area of Body 
Region Equivalent of One 
Handprint
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae and groin)
30
3.33%
Lower Limbs (including buttocks)
40
2.5%
Area Score
The extent (%) to which each of the four body regions is involved with AD (by using Table 6
above) is categorized using a non-linear scaling method to a numerical area score according 
to the following BSA scoring criteria (Table 7).
Table 7.
EASI Area Score Criteria
Percent BSA with AD 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 8). 
Table 8.
EASI Body Region Weighting
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and groin)
0.3
Lower Limbs (including buttocks)
0.4
Calculation of EASI Score 
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 the following equation.
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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. Since the scalp, palms and soles will be excluded from 
the EASI assessment in this study (even if palms and soles are being treated with the IP), the 
maximum possible score will be less than 72.0.
8.1.2.2. Investigator’s Global Assessment (IGA)
The IGA of AD is scored on a 5-point scale ranging from 0 (clear) to 4 (severe), reflecting a 
global consideration of the erythema, induration and scaling.  The clinical evaluator of AD 
will perform an assessment of the overall severity of AD and assign an IGA score and 
category as described below. The assessment will be a static evaluation without regard to the 
score at a previous visit. 
Table 9.
Investigator’s Global Assessment (IGA) Score
Score
Category
Description*
0
Clear
Atopic dermatitis (AD) is cleared, except for any residual discoloration 
(post-inflammatory hyperpigmentation and/or hypopigmentation).
1
Almost Clear
Overall, the AD 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 AD 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 AD 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 AD 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.
* The IGA will exclude scalp, palms, and soles from the assessment/scoring.
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8.1.2.3. BSA with AD
Assessment of BSA involved in AD is performed separately for four areas of the body: head
(including neck), upper limbs, trunk (including axillae and groin), and lower limbs (including 
buttocks).  The percentage surface area affected by AD is estimated by means of the 
“handprint method”, where the full hand of the participant (ie, the participant’s fully 
extended palm, fingers and thumb together) represents approximately 1% of the total BSA.
Refer to Table 6 to identify the surface area equivalent of 1 handprint in each respective body 
region.
Body region value is then summed across all four body regions resulting in a total BSA with 
AD as described in the following equation:
BSA (%) =0.1Sh + 0.2Su + 0.3St + 0.4Sl
where S = body region surface area with AD; h = head & neck; u = upper limbs; t = trunk; l = lower limbs. 
BSA with AD for Efficacy Assessment (Efficacy BSA)
BSA with AD for efficacy evaluation excludes scalp, palms, and soles.
BSA with AD for IP Need (Treatable BSA)
Evaluation of BSA for IP need is the total BSA across all body locations being treated with 
the IP.  BSA for IP need evaluation method will be the same as the BSA with AD for 
efficacy assessment, except that the BSA for IP need will include AD on all IP treated body 
locations (including palms and soles but not scalp).  If a participant has AD on palms, and/or 
soles, these body locations will be included in the BSA for IP need estimation.
Investigational product should be applied to the BSA determined at Day 1 throughout the 
treatment period regardless of clearing or improvement of AD.  Any new AD on 
treatment-eligible locations occurring after Day 1 should also be treated with the IP.  
Therefore, the BSA for IP requirements at subsequent visits should be equal to or greater 
than the value at Day 1.
A checklist of body site areas currently affected by AD (body map) will be completed at the 
Day 1 visit.  The body map will be reviewed at every visit to the site to update for any new, 
treatable areas, if needed.
8.1.3. Patient Reported Outcome Measures for AD
Every effort should be made for the participant to complete all patient reported outcome
(PRO) questionnaires before any other evaluations. The amount of time required for 
participants to complete the PRO questionnaires is approximately 10-30 minutes (depending 
on the visit and associated PROs). The PROs should be checked for completeness by the 
study site staff at every in-clinic visit.
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Participants will be provided a handheld device (provided by the Sponsor) for dosing diary 
and electronic patient-reported-outcomes (ePROs) or paper versions of the above to be 
completed at home as per the time points defined in the SoA. The clinic sites may use paper 
versions of PROs.
The following PROs will be completed only on study visit days identified in SoA,
 
PP-NRS will be used by participants for daily completion of PROs at home, starting from the 
screening visit or at least 7 days prior to the dosing/randomization day (Day 1) and as defined 
in the SoA.
All participants will complete PROs at follow-up visit in clinic.
Delegated site staff will monitor completion of PROs for adherence and will review 
adherence with participants at each visit and counsel as appropriate. If a participant has 
repeated non-adherence, the participant should be retrained on use of the device or filling out 
paper versions. If a participant is unable to complete ePROs due to documented technical 
issue or disability or other limitation, the participant will be permitted to enter or remain in 
the study providing that a valid alternate source of daily data entry is completed and 
reviewed by investigational site staff. No protocol deviations will be recorded in regard to 
PRO completion adherence. In the event of electronic malfunction of an ePRO or
misplacement of paper versions of the PROs, a replacement device or paper PROs will be 
shipped to the site. 
8.1.3.1. Peak Pruritus Numerical Rating Scale (PP-NRS) for AD
The PP-NRS is a daily patient-reported assessment of intensity of pruritus on an 11-point 
numerical rating scale, ranging from 0 (‘No Itch) to 10 (‘Worst Itch Imaginable’) with a 
24-hour recall period.2  The PP-NRS will be completed once daily at least 7 days prior to 
Day 1, and completed once daily every day from Day 1 to Week 6 before IP dose is applied 
preferably at the same time of each day if applicable, as noted in the SoA. Note that PP-NRS 
will be assessed daily during the 7 days immediately preceding randomization and a 
minimum of 4 daily scores out of the 7 days prior to Day 1 is required to calculate the 
baseline average score.
 
 
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EFFICACY ASSESSMENTS FOR PSORIASIS
All efficacy assessments of psoriatic skin will be based only on areas treated with IP and 
excluding scalp, palms, soles, nails from the assessment/scoring.
8.1.4. Physician Assessments for Psoriasis
8.1.4.1. Psoriasis Area and Severity Index (PASI)
PASI quantifies the severity of a participant’s psoriasis based on both lesion severity and the 
percentage of body surface area affected.11
Lesion Severity Score
The basic characteristics of psoriatic lesions (erythema, induration and scaling) provide a 
means for assessing the severity of lesions.  Assessment of these three main signs is 
performed separately for four areas of the body: head, upper limbs, trunk, and lower limbs.  
Average erythema, induration and scaling are rated for each body area according to a 5-point 
scale: 0, no involvement; 1, slight; 2, moderate; 3, marked; 4, very marked.  Appropriate 
morphologic descriptors for each severity score are shown in Table 10.
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Table 10.
Component Scoring Criteria for PASI*
Component Score
Description
Erythema (E)
0
No involvement
None; may have residual hyperpigmentation
1
Slight
Pink or light red
2
Moderate
Darker pink-red
3
Marked
Red
4
Very Marked
Extremely red, “beefy” red
Induration (I)
0
No involvement
None
1
Slight
Minimal elevation relative to normal surrounding skin
2
Moderate
Easily palpable with rounded edges
3
Marked
Elevated with hard, sharp borders
4
Very Marked
Very elevated with very hard, sharp borders
Scaling (S)
0
No involvement
None
1
Slight
Mainly fine scale, some lesion partially covered
2
Moderate
Coarser thin scale, most lesions partially covered
3
Marked
Coarser thick scale, nearly all lesions covered, rough
4
Very Marked
Very thick scale, all lesions covered, very rough
* The PASI will exclude scalp, palms, soles, nails from the assessment/scoring.
BSA with Psoriasis for PASI Assessment (excluding scalp, palms, soles and nails)
BSA affected by psoriasis should be calculated in each of the four body regions ie, head and 
neck (h), upper extremities (u), trunk (t), and lower extremities (l).  The area within each 
body region with the key signs of the disease is estimated using handprint as a measure, 
where the full palmar hand of the participant (ie, the participant’s fully extended palm, 
fingers and thumb together) represents approximately 1% of the total BSA.
Each region is typically assigned proportionate body surface areas of 10 (h), 20 (u), 30 (t), 
and 40 (l) handprints respectively.  Refer to Table 11 to identify the surface area equivalent 
of 1 handprint in each respective body region.
Table 11.
Handprint Determination of Body Region Surface Area for Psoriasis
Body Region
Total Number of Handprints 
in Body Region
Surface Area of Body 
Region Equivalent of One 
Handprint
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae and groin)
30
3.33%
Lower Limbs (including buttocks)
40
2.5%
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Area Score
The extent (%) to which each of the four body regions is involved with psoriasis (by using 
Table 11 above) is categorized using a non-linear scaling method to a numerical area score 
according to the following BSA scoring criteria (Table 12).
Table 12.
PASI Area Score Criteria
Percent BSA with psoriasis 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 13).
Table 13.
PASI Body Region Weighting
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and groin)
0.3
Lower Limbs (including buttocks)
0.4
Calculating of PASI score
In each body region, the sum of the Severity Scores for erythema, induration and scaling 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 a PASI score as 
described in the following equation:
PASI = 0.1Ah(Eh+Ih+Sh) + 0.2Au(Eu+Iu+Su) + 0.3At(Et+It+St) + 0.4Al(El+Il+Sl)
A = Area Score; E = erythema; I = induration/papulation; S=scaling; h = head and neck; u = upper limbs;
t = trunk; l = lower limbs.
The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0*, with higher scores 
representing greater severity of psoriasis.  
*Since the scalp, palms, soles and nails will be excluded from the PASI assessment in this 
study (even if palms and soles are being treated with the IP), the maximum possible score 
will be less than 72.0.
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8.1.4.2. Physician Global Assessment 
The Physician Global Assessment (PGA) of psoriasis is scored on a descriptive 5-point 
scale.12  The 5-point scale for PGA is: 0, “clear”; 1, “almost clear”; 2, “mild”; 3, “moderate”; 
4 “severe” (Table 14). The assessment will be a static evaluation without regard to the score 
at a previous visit.
Table 14.
Physician Global Assessment (PGA) Score
Physician’s Global 
Assessment
Description
0
Clear
No signs of psoriasis; post-inflammatory hyperpigmentation may be present
1
Almost Clear
No thickening; normal to pink coloration; no to minimal focal scaling
2
Mild
Just detectable to mild thickening; pink to light red coloration; predominantly fine 
scaling
3
Moderate
Clearly distinguishable to moderate thickening; dull to bright red, clearly 
distinguishable to moderate thickening; moderate scaling
4
Severe
Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse
scaling covering almost all or all lesions
8.1.4.3. BSA with Psoriasis 
Assessment of body surface area (BSA) involved in psoriasis is performed separately for four 
areas of the body: head (including neck), upper limbs, trunk (including axillae and groin), 
and lower limbs (including buttocks).  The percentage surface area affected by psoriasis is 
estimated by means of the “handprint method”, where the full hand of the participant (ie, the 
participant’s fully extended palm, fingers and thumb together) represents approximately 
1% of the total BSA. Refer to Table 11 to identify the surface area equivalent of 1 handprint 
in each respective body region.
Body region value is then summed across all four body regions resulting in a total BSA with 
psoriasis as described in the following equation:
BSA (%) =0.1Sh + 0.2Su + 0.3St + 0.4Sl
where S = body region surface area with psoriasis; h = head & neck; u = upper limbs; t = trunk; l = lower limbs.
BSA with Psoriasis for Efficacy Assessment (Efficacy BSA)
BSA with psoriasis for efficacy evaluation excludes scalp, palms, soles, and nails.
BSA with Psoriasis for IP Need (Treatable BSA)
Evaluation of BSA for IP need is the total BSA across all body locations being treated with 
the IP.  BSA for IP need evaluation method will be the same as the BSA with psoriasis for 
efficacy assessment, except that the BSA for IP need will include psoriasis on all IP treated 
body locations (including palms and soles but not scalp and nails).  If a participant has 
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psoriasis on palms, and/or soles, these body locations will be included in the BSA for IP need 
estimation.
Investigational product should be applied to the BSA determined at Day 1 throughout the 
treatment period regardless of clearing or improvement of psoriasis.  Any new psoriasis on 
treatment-eligible locations occurring following Day 1 should also be treated with the IP.  
Therefore, the BSA for IP need at subsequent visits should be equal to or greater than the
value at Day 1.
A checklist of body site areas currently affected by psoriasis (body map) will be completed at 
the Day 1 visit.  The body map will be reviewed at every visit to the site to update for any 
new, treatable areas, if needed.
8.1.5. Patient Reported Outcome Measures for Psoriasis
Every effort should be made for the participant to complete all patient reported outcome 
(PRO) questionnaires before any other evaluations. The amount of time required for 
participants to complete the PRO questionnaires is approximately 10-30 minutes (depending 
on the visit and associated PROs). The PROs should be checked for completeness by the 
study site staff at every in-clinic visit.
Participants will be provided a handheld device (provided by the Sponsor) for dosing diary
and electronic patient-reported-outcomes (ePROs) or paper versions of the above to be 
completed at home as per the time points defined in SoA. The clinic sites may use paper 
versions of PROs.
The following PROs will be completed only on study visit days identified in SoA,
 
 PSI will 
be used by participants for daily completion of PROs at home, starting from the screening 
visit or at least 7 days prior to the dosing/randomization day (Day 1) and as defined in the 
SoA.
8.1.5.1. Psoriasis Symptom Inventory (PSI) for Psoriasis
PSI is a self-administered 8 item questionnaire that measures the severity of psoriasis 
symptoms over the past 24 hours and the past 7 days.13 The PSI will be completed once 
daily at least 7 days prior to Day 1 using a recall period of 24 hours. For the first 2 weeks up 
to Week 2 visit (inclusive), the PSI will also be administered daily using a recall period of 
24 hours. After Week 2 visit, the PSI will be administered according to the SoA using a 
recall period of past 7 days. The measure includes concepts of itch, pain, burning, stinging, 
cracking, scaling, flaking, and redness. Patients are asked to respond to each item using a 
5-point Likert response scale: 0: not all severe, 1: mild, 2: moderate, 3: severe and 4: very 
severe. 
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8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Medical History
Investigators should make all reasonable efforts to obtain an accurate and complete medical 
history and history of prior medication use when evaluating whether a participant is eligible 
for the study.  The following will be collected at Screening: complete medical history, AD or 
psoriasis disease history (including disease duration and prior treatments) and alcohol and 
tobacco use history.
Complete AD or psoriasis disease history includes collection of details of AD or psoriasis at 
Screening: AD or psoriasis diagnosis, the use of topical treatments, systemic treatments and 
other treatments for AD or psoriasis taken during the 180 days prior to Screening with dose, 
duration of treatment, and reason for discontinuation.  All other drugs (including sunscreen, 
over the counter medication, vitamins, and dietary supplements) taken within 28 days prior to 
the Screening visit should be recorded.
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Medical history in addition to AD or psoriasis history including disease duration will be 
collected at screening. Medical history also includes history of alcohol and tobacco use.  
Smoking status and average weekly alcohol consumption (units/week) will be collected, 
where a unit contains 12 g of pure alcohol, an amount equivalent to that contained in 
5 oz/150 mL (a glass) of wine, 12 oz/360 mL of beer, or 1.5 oz/45 mL of 90 proof of spirits. 
If the status of a participant’s medical history is in doubt or information pertaining to a 
critical variable is conflicting, every reasonable step to secure proper documentation of 
correct medical status should be attempted.  Documentation of the medical and medication 
histories over the protocol defined time periods should be available for sponsor review 
during the source data verification process.  Questions about prior medications or eligibility 
should be directed to the Sponsor Clinician or Sponsor Medical Monitor.
Medical History will be collected at the Screening visit, and reviewed at Baseline Day 1 visit 
of any changes.
8.2.2. Physical Examinations (Including Height and Weight)
Physical examinations, including complete physical examination, targeted physical 
examination, height and weight will be performed at times specified in the SoA.
Physical examinations must be performed by the investigator, sub-investigator, or a qualified 
healthcare professional per local guidelines. Investigators should pay special attention to 
clinical signs related to previous serious illnesses.
A Complete physical examination will include, at a minimum, assessments of the general 
appearance, skin (presence of rash), HEENT (head, eyes, ears, nose and throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), abdomen 
(palpation and auscultation), musculoskeletal (presence of peripheral edema), neurologic 
(mental status, station, gait, reflexes, motor and sensory function, coordination) and lymph 
nodes.
A Targeted physical examination consists of skin, heart, lungs, abdomen, and examination of 
body systems where there are symptom complaints by the participants.
It is recommended that weight be measured in kilograms (kg) to the nearest 0.1 kg and that 
height be measured in centimeters (cm) with shoes removed. 
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.
Please see Section 8.2.7 for skin Local Tolerability Assessment.
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8.2.3. Vital Signs
Temperature (oral or tympanic temperature), pulse rate, and blood pressure will be assessed.
Blood pressure and pulse rate measurements will be assessed with the participant in a supine 
position using 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).
Assessment of vital signs should precede blood draw for clinical laboratory visits.
Body temperature will be collected using the tympanic or oral methods and the same method 
should be used consistently throughout the study. 
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 QTcF intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) is not 
recommended 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 10 minutes in a supine position. 
During screening, if participants have initial screening value QTcF >450 milliseconds (ms), 
ECG should be repeated two more times and the average of the three QTcF should be used to 
determine the participant eligibility.
To ensure safety of the participant, a qualified individual (eg, sub-investigator) at the 
investigator site will make comparisons to baseline measurements taken at Day 1. In the 
event of marked prolongation of the QTcF interval to >500 msec or >60 msec change from 
baseline (Day 1), the ECG should be repeated two more times and the average of the three 
QTcF should be used to determine the discontinuation of study intervention (Section 7.1
Discontinuation of Study Intervention).
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or 
b) an absolute QTcF 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 criterion listed above after 8 hours 
of monitoring (or sooner, at the discretion of the investigator).
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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 
QTcF 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 7.
8.2.5. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the 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 and the SoA. 
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. 
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 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.6. Suicidal Ideation and Behavior Risk Monitoring - Columbia Suicide Severity 
Rating Scale (C-SSRS)
The C-SSRS is a validated tool for investigative staff to use to evaluate suicidal ideation and 
behavior.14  At the Screening visit, per Exclusion Criterion #2, if there is suicidal ideation 
associated with actual intent and/or plan in the past year, or previous history of suicidal 
behaviors in the past 5 years, the participant will not be included in the study.  Trained site 
staff is to administer the C-SSRS to all participants at Screening and assess the participant’s 
eligibility based on the answers.
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For participants meeting exclusionary results of the C-SSRS, it is recommended that the 
participant’s primary care physician (PCP) should be informed, and the participant referred 
to a mental health professional, either by the PCP or the investigator according to their usual 
practice. 
8.2.7. Local Tolerability Assessment
The investigator or designee will assess tolerability at the site of IP application (pre-dose and 
immediately post-dose).  
 
All participant reported and observed application site AEs should be 
recorded along with the body region location, severity, duration and outcome as indicated on 
the CRF. See Section 7.1 for permanent and temporary discontinuation criteria based on 
local tolerability assessment. 
8.2.8. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Serum pregnancy tests are required at Screening visit only. 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.
Two negative pregnancy tests are required before randomization (1 negative serum 
pregnancy test at Screening and 1 negative urine pregnancy test at Day 1 visit).
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If urine pregnancy test is positive after study intervention application, serum pregnancy test
will be conducted, study intervention application paused and sponsor clinician and sponsor 
medical monitor notified immediately.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days, except as indicated below after the last administration of the 
study intervention or until study completion or withdrawal, whichever is longer.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
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Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 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/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, 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. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:
•
A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.
•
A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.
•
A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure.  Below are examples of 
environmental exposure during pregnancy:  
•
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact.
•
A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion or skin contact then exposes his female partner prior to
or around the time of conception.
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The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
•
If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after 
the last dose.
•
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
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 
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the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if:
•
A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
•
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.  
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the CT SAE Report Form.  Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events 
Not applicable.
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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.8.1. Lack of Efficacy
Lack of efficacy is reportable to Pfizer Safety only if associated with an SAE.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:
•
Medication errors involving participant exposure to the study intervention;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately within 
24 hours.
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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of study intervention greater than one dose within a 12-hour time 
period will be considered an overdose.  
The maximum surface area of administration is 22% BSA for AD and 16.5% for psoriasis 
participants. Investigators should be aware that administration to significantly greater area 
may also be treated as an overdose at Investigator discretion.
The Sponsor does not recommend 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 28 calendar days after the overdose of study intervention.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
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8.9. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.10. 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.
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9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands for AD
The primary estimand will be the population average treatment effect on percent change from 
baseline in EASI score relative to vehicle at 6 weeks in the absence of prohibited medication 
without regard to compliance. All observations after the initiation of prohibited medication 
will be set to missing.  Missing data from all causes, including post-randomization prohibited 
medication use will be imputed in the PF-07038124 arms using a copy to control method 
(ie, missing data in 0.01% QD regimen will be imputed from the distribution of participants 
on QD vehicle).  Participants with inadequate compliance will have their recorded EASI 
scores used as is in the analysis.  The population-based treatment effect will be the 
differences in the mean change from baseline in treatment arm compared to the vehicle. 
The secondary estimand will be the estimated population average treatment effect on the 
rates of IGA response (participants with a score of 0 or 1 and a 2 point or greater decrease 
from baseline) at Week 6 relative to vehicle without regard to compliance with IP in the 
absence of prohibited medication.  This is a composite estimand where success is defined as 
achievement of an IGA response as defined above while remaining on study, providing data 
and not taking prohibited medication; lack of compliance or adverse events will not be 
counted as a failure.  The population-based treatment effect will be the differences in the 
proportions of success in each treatment arm compared to the corresponding vehicle.  
EASI 75 and other EASI scores will be treated in a similar manner.
All other secondary continuous clinical endpoints will be analyzed using the primary 
estimand, while all other secondary categorical clinical endpoints will be analyzed using the 
secondary estimand described above. 
 
  Other estimands may be used for some of the primary and 
secondary endpoints as a means to examine the robustness of the results and to compare to 
available literature as needed.  Details of these analyses will be presented in the Statistical 
Analysis Plan (SAP).
9.1.2. Estimands for Psoriasis
The primary estimand will be the population average treatment effect on change from 
baseline in PASI scores at Week 6 relative to vehicle without regard to compliance in the 
absence of prohibited medication.  Measurements after the initiation of prohibited medication 
will be censored and treated as missing data.  Missing data due to censoring, study 
withdrawal or other reasons will have data imputed using a copy to control method 
(ie, missing data in 0.01% QD regimen will be imputed from the distribution of participants 
on QD vehicle) assuming these participants no longer receive an efficacy benefit from the IP 
but rather, have a response similar to participants assigned to vehicle. Participants with 
inadequate compliance will have their recorded PASI scores used as is in the analysis. The 
population-based treatment effect will be the differences in the mean change from baseline in 
each treatment arm compared to the corresponding vehicle. 
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The secondary estimand will be the population average treatment effect on the PGA response 
rate (percentage of participants with a score of clear (0) or almost clear (1) and ≥2 point 
improvement from baseline at Week 6 relative to vehicle without regard to compliance with 
IP in the absence of prohibited medication.  This is a composite estimand where success is 
defined as achievement of a PGA response while remaining on study, providing data and not 
taking prohibited medication; lack of compliance or adverse events will not be counted as a 
failure. The population-based treatment effect will be the differences in the proportions of 
successes in each treatment arm compared to the corresponding vehicle. 
All other key secondary continuous clinical endpoints will be analyzed using the primary 
estimand, while all other key secondary categorical clinical endpoints will be analyzed using 
the secondary estimand described above.  
 
  Other estimands may be used for some of the primary and 
secondary endpoints as a means to examine the robustness of the results and to compare to 
available literature as needed.  Details of these analyses will be presented in the SAP.
9.2. Sample Size Determination
9.2.1. Sample Size Determination for AD
The sample size calculation is based on the primary endpoint (percentage change from 
baseline in EASI score at Week 6). A total of 56 randomized participants in 1 treatment 
group and 1 vehicle group (28/arm) will provide approximately 90% power to detect a 
difference of 50 in percentage change from baseline with a common standard deviation 
48% between PF-07038124 and a vehicle arm, controlling the two-sided error rate alpha 
0.05. These calculations allow for a 25% dropout rate leaving 42 evaluable participants 
(21/arm).
For the key secondary endpoint, IGA response rate of clear or almost clear and ≥2 points 
improvement at Week 6, assuming 20% rate for vehicle and 55% rate for the treatment, this 
sample size provides 66% power controlling the two-sided error rate alpha 0.05.
9.2.2. Sample Size Determination for Psoriasis
The sample size is based on the primary efficacy endpoint, PASI change from baseline at 
Week 6. With an assumed standard deviation of 4.2 and treatment difference of 4.5, a total 
of 32 randomized participants in 2 treatment groups (16/arm) will provide approximately 
80% power for the comparison of active versus vehicle group at a two-sided significance of 
0.1. This calculation allows for an approximate 25% dropout rate, that is 12 participants 
evaluable per arm at Week 6, where evaluable is defined as included in the mITT set (defined 
in Section 9.3).
For the key secondary endpoint, PGA response rate of clear or almost clear and ≥2 points 
improvement at Week 6, assuming 20% rate for vehicle and 65% rate for the treatment, this 
sample size provides 61.9% power controlling the two-sided error rate alpha 0.05.
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9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Population
Description
Safety Analysis Set
All participants randomly assigned to IP and who apply at 
least 1 dose of IP.  Participants will be analyzed according to 
the product they actually have received.
Defined Population for 
Analysis
Description
Modified Intention to 
Treat (mITT)
All participants randomly assigned to IP and who apply at 
least 1 dose of IP.  
9.4. 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.  
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. Efficacy Analyses for AD
Endpoint
Statistical Analysis Methods
Primary: 
Percent 
Change 
from 
Baseline 
EASI at 
Week 6
A landmark analysis using analysis of covariance of percent change from 
baseline in EASI, adjusting for the baseline EASI score, to estimate the 
effect of the initially randomized treatment in the absence of prohibited 
medication regardless of treatment compliance.  The analysis will use the 
mITT analysis set.  Missing data due to any cause including censoring due 
to initiation of prohibited medication will be imputed using the 
corresponding vehicle arm, missing data in a vehicle arm will be imputed 
using data from the vehicle arm assuming data are missing at random 
(MAR).  The analysis will combine the results from the multiple 
imputations using Rubin’s rule as implemented in SAS PROC 
MIANALYZE.  
Secondary: 
IGA 
Response at 
Week 6
A landmark analysis of the composite endpoint; achieving IGA without 
prohibited medication, while remaining on study and providing data.  The
analysis will use the mITT analysis set.  Based on the definition of the 
composite endpoint all participants in the mITT set will have a response 
for all visits (ie, there is no missing data).  The proportions responding and 
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Endpoint
Statistical Analysis Methods
the corresponding risk difference comparing active treatment arm to 
vehicle group will be analyzed using the unconditional exact method; the 
risk differences and the corresponding 2-sided unconditional exact 
90% confidence intervals will be computed using Chan and Zhang 
(1999)16 method.  
Other continuous secondary endpoints at time points specified in the SoA including change 
from baseline EASI, will be analyzed as described for the primary estimand along with 
descriptive statistics and possibly graphical displays.  
Other binary secondary endpoints at time points specified in the SoA including, 
 
EASI 75, 
 IGA of clear or almost clear will be analyzed as described for 
the secondary estimand along with descriptive statistics and possibly graphical displays.  
 
9.4.2. Efficacy Analyses for Psoriasis
Endpoint
Statistical Analysis Methods
Primary: 
Change 
from 
Baseline 
PASI at 
Week 6
A landmark analysis using analysis of covariance of change from baseline 
PASI, adjusting for the baseline PASI score, to estimate the effect of the 
initially randomized treatment in the absence of prohibited medication 
regardless of treatment compliance.  The analysis will use the mITT 
analysis set. Missing data due to any cause including censoring due to 
initiation of prohibited medication will be imputed using the corresponding 
vehicle arm, missing data in a vehicle arm will be imputed using data from 
the vehicle arm assuming data are missing at random (MAR).  The analysis 
will combine the results from the multiple imputations using Rubin’s rule 
as implemented in SAS PROC MIANALYZE.  
Secondary: 
PGA 
Response at 
Week 6
A landmark analysis of the composite endpoint; achieving a PGA response 
(a score of clear (0) or almost clear (1) and ≥2 point improvement from 
baseline) without prohibited medication, while remaining on study and 
providing data. The analysis will use the mITT analysis set. Based on the 
definition of the composite endpoint all participants in the mITT set will 
have a response for all visits (ie, there is no missing data).  The 
proportions responding and the risk difference between treated arms and 
their corresponding vehicle control arm will be analyzed using an 
unconditional exact method: risk differences and corresponding 2-sided
unconditional exact 90% confidence intervals will be computed using the 
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Endpoint
Statistical Analysis Methods
Chan and Zhang (1999)16 method. 
Other continuous secondary endpoints at time points specified in the SoA including: absolute 
PASI, change from baseline PASI, percent change from baseline PASI, absolute and change 
from baseline Itch Severity Score, absolute and change from baseline Psoriasis Symptom 
Inventory will be analyzed as described for the primary estimand along with descriptive 
statistics and possibly graphical displays.  
Other binary secondary endpoints at time points specified in the SoA including, 
 
PASI 75, 
 PGA of clear or almost clear will be analyzed as described for 
the secondary estimand along with descriptive statistics and possibly graphical displays.  
9.4.3. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary
The safety data will be summarized in accordance with Pfizer Data 
Standards.  All participants who receive IP (safety population) will be 
included in the safety analyses.  All safety data will be summarized 
descriptively through appropriate data tabulations, descriptive statistics,
categorical summaries, and graphical presentations.  Safety endpoints for the 
study include:
 Treatment-emergent AEs and SAEs;
 Withdrawals from active treatment due to AEs;
 Serious infections, defined as any infection (viral, bacterial, and fungal) 
requiring hospitalization or parenteral antimicrobials;
 Safety laboratory tests (eg, hematology [including coagulation panel], 
chemistry and lipid profiles);
 Vital signs.
Change from baseline on laboratory data and vital signs will be additionally 
summarized.  Participant listings will also be produced for these safety 
endpoints.
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9.4.3.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be
summarized.
9.5. Interim Analyses
No interim analyses are planned. 
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a Data Monitoring Committee (DMC).
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
•
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 and 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.
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 guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
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10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.  The participant should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study is fully informed about his or her right to 
access and correct his or her personal data and to withdraw consent for the processing of his 
or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be 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.
Participants who are rescreened are required to sign a new ICD.
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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research. The optional 
additional research does not require the collection of any further samples.  The investigator 
or authorized designee will explain to each participant the objectives of the additional
research. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A separate 
signature will be required to document a participant's agreement to allow specimens to be 
used for additional research. Participants who decline to participate in this optional 
additional research will not provide this separate signature.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site 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 identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. 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.
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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.
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 available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals
requesting access for commercial/competitive or legal purposes.
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10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/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 (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for 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.
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The investigator(s) will notify the sponsor or its agents immediately of any regulatory
inspection 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.
10.1.7. 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.
Definition of what constitutes source data can be found in the study monitoring plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. 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 
or designee/CRO 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 GCP guidelines;
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•
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.
10.1.9. 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 
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.
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10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study team on demand (SToD) 
system. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant directly, 
and if a participant calls that number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values.  These additional tests would not require additional collection of 
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety issues.
Table 16.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count and indices 
(MCV, MCH
MCHC, RBC 
Morphology)
Reticulocytes count
WBC count with 
differential
Neutrophils (%, Abs)
Eosinophils (%, Abs)
Monocytes (%, Abs)
Basophils (%, Abs)
Lymphocytes (%, Abs)
Platelet count
BUN/urea
Creatinine
Glucose
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
Alanine transaminase 
(ALT)
Aspartate transaminase 
(AST)
Total bilirubin
Direct bilirubin a
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopy b
FSHc, e
Pregnancy test (β-hCG)d
Fibrinogen
High-sensitivity C-reactive 
protein (hsCRP)
a.
Only if total bilirubin is elevated.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
c.
For confirmation of postmenopausal status, in females who are amenorrheic for at least 12 consecutive 
months.
d.
Serum or urine β-hCG for female participants of childbearing potential per SoA. Serum pregnancy test 
must be performed at Screening.
e.
At Screening only.
Investigators must document their review of each laboratory safety report.
Laboratory/analyte results that could unblind the study will not be reported to investigator
sites or other blinded personnel until the study has been unblinded.
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition
•
An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.
•
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator  Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:
•
Is associated with accompanying symptoms.
•
Requires additional diagnostic testing or medical/surgical intervention.
•
Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.
•
Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
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Events NOT Meeting the AE Definition
•
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
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should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
•
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
•
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
•
Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.
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10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety. These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious adverse events 
(AEs); and (3) exposure to the study intervention under study during pregnancy or 
breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
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, and 
occupational exposure
None
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP supplemental 
form for EDP)  
Note: Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.
•
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.
•
The investigator will then record all relevant AE/SAE information in the CRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.
•
There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
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exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
•
Mild: An event that is easily tolerated by the participant, causing minimal
discomfort and not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.
•
Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.
•
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.
•
The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she 
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has reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.
•
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
•
If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor.  In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this causal
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the CT SAE Report Form and in accordance with the SAE 
reporting requirements.
Follow-up of AEs and SAEs
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.
•
New or updated information will be recorded in the originally completed CRF.
•
The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
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10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as the data
become available.
•
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form
•
Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.
•
In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.
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10.4. Appendix 4: Contraceptive Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements 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 reproductive safety risk of the study 
intervention(s):
•
Refrain from donating sperm.
PLUS either:
•
Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR
•
Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.
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 an acceptable contraceptive method as described below 
during the intervention period (for a minimum of 28 days after the last dose of study 
intervention).  The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
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.
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Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:
•
Documented hysterectomy;
•
Documented bilateral salpingectomy;
•
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female:
•
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, a
•
High 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. 
•
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.
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5. Vasectomized partner:
•
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:
•
Oral;
•
Intravaginal;
•
Transdermal;
•
Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:
•
Oral;
•
Injectable.
8. Sexual abstinence:
•
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments and 
Study Intervention Rechallenge Guidelines
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 an “adaptor” 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).
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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, 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, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) and collection of serum 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.
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events
•
Marked sinus bradycardia (rate <40 bpm) lasting minutes.
•
New PR interval prolongation >280 msec.
•
New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.
•
New-onset atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.
•
New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration.
•
Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive ventricular 
complexes.
ECG Findings That May Qualify as Serious Adverse Events
•
QTcF prolongation >500 msec.
•
New ST-T changes suggestive of myocardial ischemia.
•
New-onset left bundle branch block (QRS >120 msec).
•
New-onset right bundle branch block (QRS >120 msec).
•
Symptomatic bradycardia.
•
Asystole:
•
In awake, symptom-free patients in sinus rhythm, with documented periods of 
asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node; 
•
In awake, symptom-free patients with atrial fibrillation and bradycardia with 
1 or more pauses of at least 5 seconds or longer; 
•
Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.
•
Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).
•
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (heart 
rate <40 bpm), accelerated idioventricular rhythm (HR 40 bpm to <100 bpm), and 
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monomorphic/polymorphic ventricular tachycardia (HR >100 bpm (such as
torsades de pointes)).
•
Type II second-degree (Mobitz II) AV block.
•
Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events
•
Change in pattern suggestive of new myocardial infarction.
•
Sustained ventricular tachyarrhythmias (>30 seconds’ duration).
•
Second- or third-degree AV block requiring pacemaker placement.
•
Asystolic pauses requiring pacemaker placement.
•
Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.
•
Ventricular fibrillation/flutter.
•
At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.
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10.8. Appendix 8: Country-Specific Requirements
Not applicable.
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10.9. Appendix 9: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
10.9.1. 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 SoA or unscheduled 
visits. Telehealth visits may be used to continue to assess participant safety and collect data 
points where allowable by national law or by local guidance. 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 study intervention(s), including compliance and missed doses.
•
Review and record any AEs and SAEs since the last contact.  Refer to Section 8.3.
•
Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.
•
Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4 and Section 10.9.2.1 of this appendix regarding 
pregnancy tests.
•
Local Tolerability Assessments. 
•
Efficacy Assessments (See Section 10.9.6).
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
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10.9.2. Alternative Facilities for Safety Assessments
10.9.2.1. 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: 
•
List safety laboratory evaluations, including pregnancy testing (See Table 16 Protocol 
Required Safety Laboratory Assessments).
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. 
10.9.2.2. 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. 
A copy of the ECG should be available as source documents for review.
10.9.3. 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.
In situations where participants are quarantined or self-isolating, arrangements to send study 
intervention via courier may be implemented where allowable by national law or by local 
guidance and with the participant’s verbal consent documented on the Provision of Critical 
Study Information Form (if applicable). The decision to supply requires the investigator to 
obtain and evaluate protocol-specified safety laboratory tests, pregnancy tests (for female 
subjects of childbearing potential), ECGs, contraception, concomitant treatment, and adverse 
events.
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Study intervention may be shipped by courier to study participants if permitted by local 
regulations and in accordance with storage and transportation requirements for the study 
intervention.  Pfizer does not permit the shipment of study intervention by mail. The
tracking record of shipments and the chain of custody of study intervention must be kept in 
the participant’s source documents/medical records.
10.9.4. Home Health Visits
A home health care service may be utilized to facilitate scheduled visits per the Schedule of 
Activities.  Home health visits include a healthcare provider conducting an in-person study 
visit at the participant’s location, rather than an in-person study visit at the site. Home health 
visits may be implemented if it is not possible for participants to attend a study visits at the 
site and where allowable by national law or by local guidance. The following may be 
performed during a home health visit:
•
Review and record study intervention(s), including compliance and missed doses.
•
Review and record any AEs and SAEs since the last contact.  Refer to Section 8.3.
•
Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.
•
Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4 and Section 10.9.2.1 of this appendix regarding 
pregnancy tests.
•
ECG.
•
Vital signs.
•
Physical assessment.
•
Laboratory sample, 
•
Collect and weigh previous IP tubes.
•
Dispensing of IP.
•
IP application and observation.
•
Local Tolerability Assessments. 
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10.9.5. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an adverse event 
(AE) or serious adverse events (SAE) and appropriate medical intervention provided. 
Temporary discontinuation of the study intervention may be medically appropriate until the 
participant has recovered from COVID-19.
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
10.9.6. Efficacy Assessments
If remote video visit is feasible and is being conducted as part of the Telehealth Visit in the 
event that in-clinic study visits cannot be conducted, the following procedures and 
assessments may be considered: 
•
Efficacy Assessments for AD, including EASI, IGA, and BSA.
•
Efficacy Assessments for psoriasis, including PASI, PGA and BSA.
Only qualified raters will be allowed to evaluate participants remotely.
10.9.7. Independent Oversight Committees
Not applicable.
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10.10. Appendix 10: Prohibited Prior and Concomitant Medications
10.10.1. Prohibited Prior and Concomitant Medications
Drug Category 
Drugs (Examples below)
Required Washout Period 
Requirement Prior to 
Day 1/Randomization
Any cell depleting 
agents
rituximab or other selective 
B-lymphocyte depleting agents 
(including experimental agents), 
alemtuzumab (Lemtrada® or 
CamPath®), alkylating agents 
(eg, cyclophosphamide or 
chlorambucil), total lymphoid 
irradiation, etc.
6 months or 5 half-lives (if known),
whichever is longer, or until lymphocyte 
count returns to normal, whichever is 
longer.
IL-17 inhibitor, IL-
12/23 inhibitor, or 
IL-23 inhibitor
secukinumab (Cosentyx®), ixekizumab 
(Taltz®), ustekinumab (Stelara®), 
brodalumab (Siliq®), guselkumab 
(Tremfya®), risankizumab (Skyrizi®),
tildrakizumab (Ilumya®), and 
bimekizumab,
12 weeks.
TNF inhibitor
adalimumab (Humira® or biosimilars),
certolizumab (Cimzia®), golimumab
(Simponi® and Simponi Aria®).
10 weeks or 5 half-lives (whichever is 
longer) (Note: Infliximab (Remicade® or 
biosimilars) 8 weeks, Etanercept 
(Enbrel® or biosimilars) 4 weeks).
Other biologics
dupilumab (Dupixent®), efalizumab 
(Raptiva®), abatacept (Orencia®).
12 weeks unless otherwise specified in
this table.
Topical PDE4
inhibitors (anywhere 
on the body), oral 
PDE4 inhibitors
crisaborole (Eucrisa®), roflumilast
(Daliresp®, ARQ-151), apremilast 
(Otezla®).
6 weeks.
Systemic 
corticosteroids (oral, 
parenteral)
4 weeks 
(stable use /regular regimen of 
intranasal/inhaled/ophthalmic
corticosteroids with ≥14 days of 
consistent use prior to 
Day 1/Randomization are permitted to
continue but must not alter or stop
regimen during the study).
Systemic 
immunosuppressive 
agents and other oral 
nonbiologic 
treatments
methotrexate, leflunomide, 
sulfasalazine, hydroxychloroquine, 
azathioprine, cyclosporine, mizoribine, 
tacrolimus, mycophenolate mofetil 
(MMF), hydroxycarbamide
(hydroxyurea), fumaric acid 
derivatives, acitretin.
4 weeks.
Oral JAK inhibitors
tofacitinib (Xeljanz®), baricitinib 
(Olumiant®), upadacitinib, peficitinib, 
filgotinib.
4 weeks.
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Drug Category 
Drugs (Examples below)
Required Washout Period 
Requirement Prior to 
Day 1/Randomization
Interferon gamma
interferon gamma-1b (Actimmune®).
4 weeks.
Light therapy etc.
sunbathing, tanning bed use, or light 
therapy ultraviolet (UV), ultraviolet B
(UV-B), psoralen-UV-A [PUVA]), 
excimer laser (308 nm).
4 weeks.
Topical retinoids,
Vitamin D analogues,
benzoyl peroxide
(BPO), anthralin
(dithranol), 
keratolytics (salicylic 
acid), tars, on study 
treatable lesions
tazarotene, calcipotriene.
2 weeks (stable regimen with ≥14 days 
of consistent use prior to 
Day 1/Randomization and not on the 
study treatable lesions are permitted to 
continue but must not alter or stop their 
regimen during the study.
Systemic antibiotics
2 weeks (Short courses (≤14 days) of 
systemic antibiotics may be given during 
the study if clinically necessary for the 
treatment of new onset infections).
Topical 
corticosteroids 
(TCS), class I to V, 
anywhere on the 
body
betamethasone, clobetasol, diflorasone,
halobetasol, amcinonide, 
desoximetasone, fluocinonide, 
halcinonide, mometasone,
triamcinolone, clocortolone,
flurandrenolide, fluticasone,
fluocinolone, prednicarbate,
hydrocortisone butyrate, 
hydrocortisone probutate, 
hydrocortisone valerate.
2 weeks.
Topical calcineurin 
inhibitor (TCI), 
anywhere on the 
body
topical tacrolimus (Protopic®), topical 
pimecrolimus (Elidel®).
2 weeks.
Topical 
antihistamines 
anywhere on the 
body
doxepin.
2 weeks (topical antihistamines for 
seasonal allergies are allowed provided 
stable doses within 7 days of 
Day 1/Randomization). 
Topical antibacterial 
medications or 
products, including 
soaps, bleach baths, 
or topical sodium 
hypochlorite-based 
products anywhere 
on the body
7 days.
Systemic sedating 
antihistamines
hydroxyzine, diphenhydramine,
7 days,
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Drug Category 
Drugs (Examples below)
Required Washout Period 
Requirement Prior to 
Day 1/Randomization
Systemic non-
sedating 
antihistamines in a 
nonstable (eg,
escalating, 
decreasing, or PRN) 
regimen
cetirizine,
7 days (stable non-sedating systemic 
antihistamine regimen with ≥7 days of
consistent use prior to 
Day 1/Randomization are permitted to 
continue but must not alter or stop their 
regimen during the study).
Use of bland (non-
medicated) emollients 
on treatable lesions
24 hours (After the 
Day 1/Randomization Visit, use of bland 
(non-medicated) emollient(s) is 
permitted during the study to manage dry 
skin in areas surrounding but not on or 
overlapping the treatable lesions).
Any other biologic 
investigational 
therapy for AD, 
psoriasis or psoriatic 
arthritis
6 months unless otherwise specified in
this table.
Any other non-
biological 
investigational
therapy or procedure 
for AD, psoriasis or 
psoriatic arthritis
12 weeks unless otherwise specified in
this table.
Prohibited 
Concomitant 
Medications which 
may result in drug-
drug interaction 
See Section 10.10.2 below.
7 days or 5 half-lives (whichever is 
longer).
10.10.2. Prohibited Concomitant Medications which may result in Drug-Drug 
Interaction (DDI)  
Upon topical application of PF-07038124, systemic exposure to date has been low.  
Maximum plasma concentration has not exceeded 1 nM; which is approximately 1000-fold 
less than the IC50 values for CYP450 and UGT inhibition, as well as various transporters.  
Therefore, PF-07038124 has a low risk of any drug-drug interaction.  For more details, 
please refer to the Investigator’s Brochure.
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10.11. Appendix 11: Diagnosis Criteria for AD
Per AD Specific Inclusion Criteria, a participant is to have a clinical diagnosis of AD
according to the criteria of Hanifin and Rajka.
Hanifin and Rajka’s Diagnostic Criteria for AD
Major Criteria (must have at least three)
Pruritus
Typical morphology and distribution:
Flexural lichenification in adults
Facial and extensor eruptions in infants and children
Chronic or chronically-relapsing dermatitis
Personal or family history of atopy (asthma, allergic rhinitis, AD)
Minor Criteria (must have at least three)
Xerosis
Ichthyosis/keratosis pilaris/palmar hyperlinearity
Immediate (type 1) skin test reaction
Elevated serum IgE
Early age of onset
Tendency toward cutaneous infections (esp. staph. aureus and herpes simplex), impaired cell-mediated 
immunity
Tendency toward non-specific hand or foot dermatitis
Nipple eczema
Cheilitis
Recurrent conjunctivitis
Dennie-Morgan infraorbital fold
Keratoconus
Anterior subcapsular cataracts
Orbital darkening
Facial pallor, facial erythema
Pityriasis alba
Anterior neck folds
Itch when sweating
Intolerance to wool and lipid solvents
Periofollicular accentuation
Food intolerance
Course influenced by environmental and emotional factors
White dermographism, delayed blanch
Hanifin J, Rajka G. Diagnostic features of atopic dermatitis Acta Derm Venereol. 1980;92:44.7
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10.12. Appendix 12: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
Absolute
AD
Atopic Dermatitis
AE
Adverse Event
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
AUC
Area Under the Curve
AV
Atrioventricular
β-hCG
Beta-Human Chorionic Gonadotropin
BID
Twice Daily
BLQ
Below the Limit of Quantification
BMI
Body Mass Index
bpm
Beats Per Minute
BSA
Body Surface Area
BUN
Blood Urea Nitrogen
cAMP
Cyclic Adenosine Monophosphate
Cav
Average Concentrations
CFR
Code of Federal Regulations
cGMP
Cyclic Guanosine Monophosphate
CIOMS
Council for International Organizations of Medical Sciences
CK
Creatine Kinase
Cmax
Peak Plasma Concentrations
CO2
Carbon Dioxide (Bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
CRF
Case Report Form
CRO
Contract Research Organization
C-SSRS
Columbia Suicide Severity Rating Scale
CSR
Clinical Study Report
CT
Clinical Trial
DCT
Data Collection Tool
DDI
Drug-Drug Interaction
DILI
Drug-Induced Liver Injury
DMC
Data Monitoring Committee
DU
Dispensable Unit
EASI
Eczema Area and Severity Index
EC
Ethics Committee
ECG
Electrocardiogram
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Abbreviation
Term
eCRF
Electronic Case Report Form
EDP
Exposure During Pregnancy
EFD
Embryo-Fetal Development
eGFR
Estimated Glomerular Filtration Rate
EMA
European Medicines Agency
EOS
End of Study
EOT
End of Treatment
ePRO
Electronic Patient-Reported Outcomes
ET
Early Termination
EU
European Union
EudraCT
European Clinical Trials Database
FIH
First-in-Human
FSH
Follicle-Stimulating Hormone
FTU
Fingertip Unit
GCP
Good Clinical Practice
GGT
Gamma-Glutamyl Transferase
HEENT
Head, Eyes, Ears, Nose and Throat
HIPAA
Health Insurance Portability and Accountability Act
HR
Heart Rate
HRT
Hormone Replacement Therapy
hsCRP
High-sensitivity C-reactive protein
IB
Investigator’s Brochure
IC50
half maximal inhibitory concentration
ICD
Informed Consent Document
ICH
International Council for Harmonisation
ID
Identification
IGA
Investigator’s Global Assessment
IgE
Immunoglobulin E
IL
Interleukin
IMP
Investigational Medicinal Product
IND
Investigational New Drug
INR
International Normalized Ratio
IP
Investigational Product
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
IRC
Internal Review Committee
IRT
Interactive Response Technology
IWR
Interactive Web-Based Response
JAK
Janus Kinase
LBBB
Left Bundle Branch Block
LFT
Liver Function Test
MCH
Mean Corpuscular Hemoglobin
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Abbreviation
Term
MCHC
Mean Corpuscular Hemoglobin Concentration
MCV
Mean Corpuscular Volume
mITT
Modified Intention to Treat 
MMF
Mycophenolate Mofetil
MRHD
Maximum Recommended Human Dose
msec
Millisecond
N/A
Not Applicable
NIMP
Noninvestigational Medicinal Product
NOAEL
No-Observed-Adverse-Effect Level
NOEL
No Observed Effect Level
PASI
Psoriasis Area and Severity Index
PBMC
Peripheral Blood Mononuclear Cell
PD
Pharmacodynamic(S)
PDE
Phosphodiesterase
PDE4
phosphodiesterase 4
PFS
Prefilled Syringe
PGA
Physician Global Assessment
PK
Pharmacokinetic(S)
PP-NRS
Peak Pruritus Numerical Rating Scale
PRO
Patient Reported Outcomes
PSI
Psoriasis Symptom Inventory
PUVA
Psoralen – Ultraviolet A
PVC
Premature Ventricular Contraction/Complex
QD
Once Daily
QoL
Quality of Life
QTc
Corrected QT
QTcF
QTc Corrected Using Fridericia’s Formula
Qual
Qualitative
Rac
Accumulation Ratio
RBC
Red Blood Cell
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SoA
Schedule of Activities
SOP
Standard Operating Procedure
SRSD
Single Reference Safety Document
SToD
Study Team on Demand
SUSAR
Suspected Unexpected Serious Adverse Reaction
t½
terminal half-life 
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Abbreviation
Term
TBili
Total Bilirubin
TCI
Topical Calcineurin Inhibitor
TCS
Topical Corticosteroids
Th2
T-Helper 2 Cells
TNF
Tumor Necrosis Factor
uCav
Unbound Average Concentrations
ULN
Upper Limit of Normal
US
United States
UV
Ultraviolet
UVA
Ultraviolet A
UVB
Ultraviolet B
WBC
White Blood Cell
WOCBP
Woman of Childbearing Potential
WONCBP
Woman of Non-Childbearing Potential
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11. REFERENCES
1.
Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387: 1109-22.
2.
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. British Journal of Dermatology 2019; 181: 761-9
3.
Nestle FO, Kaplan DH, Barker J. Psoriasis. New England Journal of Medicine 2009; 
361: 496-509.
4.
Sbidian E, Chaimani A, Afach S, et al. Systemic pharmacological treatments for chronic 
plaque psoriasis: a network meta‐analysis. Cochrane Database of Systematic Reviews
2020; (1).
5.
Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a 
novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of 
atopic dermatitis (AD) in children and adults. Journal of the American Academy of 
Dermatology 2016; 75: 494-503.e6.
6.
Lebwohl MG, Papp KA, Stein Gold L, et al. Trial of Roflumilast Cream for Chronic 
Plaque Psoriasis. New England Journal of Medicine 2020; 383: 229-39.
7.
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol
1980; 92: 44–7.
8.
Tofte S, Graeber M, Cherill R, et al. Eczema area and severity index (EASI): A new 
tool to evaluate atopic dermatitis. Journal of the European Academy of Dermatology 
and Venereology 1998; 11: S197.
11.
Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. 
Dermatologica 1978; 157: 238-44.
12.
Langley RGB, Feldman SR, Nyirady J, et al. The 5-point Investigator’s Global 
Assessment (IGA) Scale: A modified tool for evaluating plaque psoriasis severity in 
clinical trials. Journal of Dermatological Treatment 2015; 26: 23-31.
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13.
Bushnell DM, Martin ML, McCarrier K, et al. Validation of the Psoriasis Symptom 
Inventory (PSI), a patient-reported outcome measure to assess psoriasis symptom 
severity. Journal of Dermatological Treatment 2013; 24: 356-60.
14.
Posner K, Brown GK, Stanley B, et al. The Columbia–Suicide Severity Rating Scale: 
Initial Validity and Internal Consistency Findings From Three Multisite Studies With 
Adolescents and Adults. American Journal of Psychiatry 2011; 168: 1266-77.
16.
Chan ISF, Zhang Z. Test-Based Exact Confidence Intervals for the Difference of Two 
Binomial Proportions. Biometrics 1999; 55: 1202-9.
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SAP_001.pdf: 
Protocol C3941002 (PF-07038124 ) Statistical Analysis Plan Amendment
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Page 1
Protocol C3941002
A PHASE 2A, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, 
PARALLEL GROUP STUDY TO ASSESS THE EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-07038124 OINTMENT FOR 
6 WEEKS IN PARTICIPANTS WITH MILD TO MODERATE ATOPIC 
DERMATITIS OR PLAQUE PSORIASIS
Statistical Analysis Plan 
(SAP)
Version:
2.0
Date:
16 June2021
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TABLE OF CONTENTS
LIST OF FIGURES ...................................................................................................................5
APPENDICES ...........................................................................................................................5
1. VERSION HISTORY............................................................................................................6
2. INTRODUCTION .................................................................................................................7
2.1. Study Objectives, Endpoints, and Estimands............................................................8
2.1.1. Primary Estimand(s)...................................................................................15
2.1.2. Secondary Estimand(s)...............................................................................16
2.1.3. Additional Estimand(s)...............................................................................17
2.2. Study Design ...........................................................................................................17
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND CONVENTIONS19
3.1. Primary Endpoint(s) ................................................................................................19
3.2. Secondary Endpoint(s) ............................................................................................20
3.4. Baseline Variables...................................................................................................22
3.5. Safety Endpoints .....................................................................................................23
3.5.1. Adverse Events...........................................................................................23
3.5.2. Laboratory Data..........................................................................................23
3.5.3. Vital Sign....................................................................................................23
3.5.4. Electrocardiograms.....................................................................................24
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................24
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................24
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5.1. Hypotheses and Decision Rules ..............................................................................24
5.2. General Methods .....................................................................................................25
5.2.1. Analyses for Binary Endpoints...................................................................25
5.2.2. Analyses for Continuous Endpoints ...........................................................26
5.2.3. Analyses for Categorical Endpoints ...........................................................26
5.2.4. Analyses for Time-to-Event Endpoints ......................................................26
5.3. Methods to Manage Missing Data ..........................................................................26
5.3.1. Efficacy Data ..............................................................................................26
6. ANALYSES AND SUMMARIES ......................................................................................28
6.1. Primary Endpoint(s) ................................................................................................28
6.1.1. Percentage Change from Baseline in EASI Score at Week 6 & Change from Baseline PASI Score at Week 6
..........................................................................................................................28
6.1.1.1. Main Analysis ...........................................................................28
6.1.1.2. Sensitivity/Supplementary Analyses.........................................28
6.2. Secondary Endpoint(s) ............................................................................................29
6.2.1. IGA/PGA Responses at Week 6.................................................................29
6.2.1.1. Main Analysis ...........................................................................29
6.2.2. Other Binary Secondary Endpoints ............................................................29
6.2.3. Other Continuous Secondary Endpoints.....................................................29
6.2.3.1. Main Analysis ...........................................................................29
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6.5. Subset Analyses.......................................................................................................31
6.6. Baseline and Other Summaries and Analyses.........................................................31
6.6.1. Baseline Summaries....................................................................................31
6.6.2. Study Conduct and Participant Disposition................................................31
6.6.3. Study Treatment Exposure .........................................................................31
6.6.4. Concomitant Medications and Nondrug Treatments..................................31
6.7. Safety Summaries and Analyses .............................................................................32
6.7.1. Adverse Events...........................................................................................32
6.7.2. Laboratory Data..........................................................................................32
6.7.3. Vital Signs ..................................................................................................32
6.7.4. Electrocardiograms.....................................................................................33
6.7.5. Physical Examination .................................................................................33
7. INTERIM ANALYSES.......................................................................................................33
8. REFERENCES ....................................................................................................................33
9. APPENDICES .....................................................................................................................34
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LIST OF FIGURES
Figure 1 Study Design Schema................................................................................................19
APPENDICES
Appendix 1. Summary of Efficacy Analyses...........................................................................34
Appendix 2. Data Derivation Details.......................................................................................36
Appendix 2.1. Definition and Use of Visit Windows in Reporting.........................................36
Appendix 3. Endpoint Derivations..........................................................................................37
Appendix 4. Sample SAS Code for Estimand 1 ......................................................................49
Appendix 5. Sample SAS Code for Estimand 2 – Risk Difference using Chan and Zhang (1999) 54
Appendix 6. Sample SAS Code for the Confidence Interval of a Binomial Proportion (Blyth-Still-Casella)
55
Appendix 7. Sample SAS Code for MMRM...........................................................................56
Appendix 8. List of Abbreviations...........................................................................................57
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1. VERSION HISTORY
This SAP for Study C3941002 is based on the protocol dated 19 August 2020.
Table 1.
Summary of Major Changes in SAP Amendments
SAP 
Version
Change
Rationale
1
Not Applicable
Not Applicable
Amendment
Section 3
Adding IGA/PGA response at other timepoints besides 
week 6 as secondary endpoint
Longitudinal profile of IGA/PGA response are of 
clinical importance
Section 6.1.1 and 6.2.3.1
Data collected for subjects after early drug discontinuation 
will not be censored.  
Estimand is irrespective of non-compliance.
Section 6.1.1.1 and 6.2.3.1
Number of multiple imputation is changed from 100 to 
1000
To increase the precision of variance estimate of the 
treatment effect based on multiple imputation
Section 6.2.3
For ANCOVA analysis at week 6 for secondary 
endpoints, multiple imputation will be used for missing 
data. 
To be consistent with primary endpoint analysis. 
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Section 6.2.3
2. INTRODUCTION
PF-07038124 is a topical phosphodiesterase 4 (PDE4) inhibitor that is being investigated for the treatment of atopic dermatitis (AD) 
and plaque psoriasis (psoriasis).
The purpose of the study is to investigate the efficacy, safety, tolerability and pharmacokinetics of topical PF-07038124 in 
participants with mild to moderate AD or mild to moderate psoriasis.  Participants will receive either PF-07038124 or a vehicle 
control for 6 weeks.
Phosphodiesterases (PDE) are a family of enzymes that breakdown the ubiquitous second messengers, cAMP and cyclic guanosine 
monophosphate (cGMP), that regulate various cellular processes.  PDE4 is a subfamily that includes the four isozymes, each encoded 
by separate genes, PDE4 A, B, C and D.  Inhibitors of the PDE4 family have been the focus of intense drug development over many 
years due to their broad potential in inflammatory diseases such as AD and psoriasis.  
PF-07038124 is a potent and selective PDE4 inhibitor intended to be used for topical administration for the treatment of AD and 
psoriasis.  PF-07038124 inhibits the enzymatic activity of the PDE4 isoforms that have been tested with a half maximal inhibitory 
concentration (IC50) of 0.505 nM and 0.3 nM on PDE4B and PDE4D, respectively.  PF-07038124 inhibits cytokine production and 
release from T cells and monocytes in peripheral blood mononuclear cells (PBMC) over a range of concentrations that is dependent 
on the cytokine that is being modulated.  The IC50 for release of lipopolysaccharide (LPS) stimulated tumor necrosis factor (TNF) ! is 
most sensitive with an IC50 of 0.15 nM.  The IC50’s for inhibition of interferon (IFN) ∀, IL-4, and IL-13 from lectin stimulated PBMCs 
are 1, 4 and 135 nM, respectively.  PF-07038124 exhibited greater inhibitory activity on IL-13 release than was seen with other PDE4 
specific inhibitors, consistent with its inhibitory activity on additional PDEs, such as PDE3 at higher concentrations.  PF-07038124 
increased the level of cAMP in human PBMCs in a dose dependent manner, consistent with its primary mechanism of action as a PDE 
inhibitor.
An ex vivo human skin model of Th2 inflammation was used to measure the activity of PF-07038124 in its ointment formulation with 
topical application.  This model has been used to test the activity of other topical therapeutic compounds, including topical
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corticosteroids, Janus kinase (JAK) inhibitors and the PDE4 inhibitor crisaborole (Eucrisa®).  In this model system with a single dose 
application on excised human skin 20 hours prior to stimulation of the T cells in the skin tissue, PF-07038124 inhibited inflammatory 
cytokine gene expression at the dose strengths of 0.1, 0.06, 0.03 and 0.01%, with little to no activity at 0.001% strength relative to the 
vehicle (placebo) control. 
Based on its cytokine inhibition profile, topical administration of PF-07038124 is anticipated to provide potential therapeutic benefit 
in the treatment of AD and psoriasis by targeting the T-helper-2 response cytokines and TNF-α.
This statistical analysis plan (SAP) provides the detailed methodology for summary and statistical analyses of the data collected in 
Study C3941002.  This document may modify the plans outlined in the protocol; however, any major modifications of the primary 
endpoint definition or its analysis will also be reflected in a protocol amendment.
2.1. Study Objectives, Endpoints, and Estimands
ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
Primary Objective 
Primary Endpoint
Primary Estimands 
#
To compare the efficacy of 
PF-07038124 versus 
vehicle on percent change 
from baseline in Eczema 
Area and Severity Index 
(EASI) in participants with 
mild or moderate atopic 
dermatitis (AD).
#
Percent change from baseline in 
EASI total score at Week 6.
#
Estimand E1: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the 
investigational product (IP) 
on a continuous endpoint; 
without the benefit of 
additional prohibited 
medications during 
treatment and regardless of 
participant compliance with 
the IP dosing.
Secondary Objectives: 
Secondary Endpoints
Secondary Estimands 
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ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
#
To compare the efficacy of 
PF-07038124 versus vehicle, 
using Investigator’s Global 
Assessment (IGA) score 
assessment as endpoint in 
participants with mild or 
moderate AD.
#
Proportion of participants 
achieving IGA score of clear (0) 
or almost clear (1) (on a 5-point 
scale) and a reduction from 
baseline of ≥2 points at Week 6
and other study visit time points 
specified in the SoA.
#
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications and regardless 
of a participant compliance 
with the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of disease 
severity and symptoms as 
endpoints in participants 
with mild or moderate AD.
#
Proportion of participants 
achieving EASI 75 
(75% improvement from 
baseline) at study visit time 
points specified in the SoA.
#
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications and regardless 
of a participant compliance 
with the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus vehicle, 
using measures of patient 
reported outcomes (PRO), in 
participants with mild or 
moderate AD.
#
Proportion of participants having 
≥4 points of reduction in weekly 
averages of Peak Pruritus 
Numerical Rating Scale 
(PP-NRS) from baseline at study 
visit time points specified in the 
SoA.
#
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications and regardless 
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ATOPIC DERMATITIS
Objectives
Endpoints
Estimands
of a participant compliance 
with the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus vehicle, 
on measures of disease and 
symptom severity in 
participants with mild or 
moderate AD.
#
Change from baseline in EASI 
total score at study visit time 
points specified in the SoA.
#
Proportion of participants 
achieving IGA score of clear (0) 
or almost clear (1) at study visit 
time points specified in the SoA.
#
Percent change from baseline in 
affected Body Surface Area (BSA) 
at study visit time points specified 
in the SoA.
#
All continuous secondary 
endpoints will be analyzed 
descriptively and using 
estimand E1 described 
above, when appropriate.
#
All categorical secondary 
endpoints will be analyzed 
descriptively and using 
estimand E2 described 
above, when appropriate.
#
To characterize the safety 
and tolerability of 
PF-07038124 versus vehicle 
in participants with mild or 
moderate AD.  
# Incidence of treatment emergent 
adverse events (AEs) and serious 
adverse events (SAEs), clinically
significant changes in vital signs, 
electrocardiogram (ECG), and 
laboratory tests.
#
Incidence of severity grades in 
skin tolerability at times indicated 
in SoA.
#
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
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PSORIASIS
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:
#
To compare the efficacy of 
PF-07038124 versus vehicle 
on change from baseline in 
Psoriasis Area and Severity 
Index (PASI) score in 
participants with mild to 
moderate plaque psoriasis. 
#
Change from baseline in PASI 
score at Week 6.
#
Estimand E1: This estimand is 
intended to provide a 
population level estimate of 
the treatment effect of the 
investigational product (IP) 
alone on a continuous 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
Secondary: 
Secondary: 
Secondary:
#
To compare the efficacy of 
PF-07038124 versus vehicle 
on Physician Global
Assessment (PGA) score in 
participants with mild to 
moderate plaque psoriasis.
#
Proportion of participants with 
PGA score clear (0) or almost 
clear (1) (on a 5-point scale) 
and ≥2 points improvement 
from baseline at Week 6 and at 
study visit time points specified 
in the SoA. 
#
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance 
with the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus vehicle 
on the proportion of 
participants with mild to 
#
Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from 
baseline) at study visit time 
points specified in the SoA.
#
Estimand E2: This estimand 
is intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
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PSORIASIS
Objectives
Endpoints
Estimands
moderate plaque psoriasis 
achieving PASI 75. 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance 
with the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus 
vehicle, using measures of 
patient reported outcomes 
(PRO), in participants with 
mild or moderate plaque 
psoriasis.
#
Proportion of participants who 
achieved a Psoriasis Symptoms 
Inventory (PSI) score of 0 (not 
at all) or 1 (mild) on every item 
at study visit time points 
specified in the SoA.
#
Estimand E2: This estimand is 
intended to provide a 
population level estimate of 
the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit 
of additional prohibited 
medications, regardless of 
participants compliance with 
the IP dosing.
#
To compare the efficacy of 
PF-07038124 versus vehicle 
on measures of disease and 
symptom severity in 
participants with mild to 
moderate plaque psoriasis. 
#
Change from baseline in PASI 
scores at study visit time points 
specified in the SoA (except 
Week 6). 
#
Percent change from baseline in 
PASI scores at study visit time 
points specified in the SoA. 
#
Proportion of participants with 
PGA score clear (0) or almost 
clear improvement from 
baseline at time points specified 
in the SoA.
#
Percent change from baseline in 
BSA at study visit time points 
specified in the SoA.
#
All other continuous 
secondary endpoints will be 
analyzed descriptively and 
using estimand E1 described 
above when appropriate.
#
All other categorical 
secondary endpoints will be 
analyzed descriptively and 
using estimand E2 described 
above when appropriate.
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PSORIASIS
Objectives
Endpoints
Estimands
#
To assess safety and 
tolerability of PF-07038124 
in participants with mild to 
moderate plaque psoriasis.
#
Incidence of treatment emergent 
adverse events (AEs) and 
serious adverse events (SAEs), 
clinically significant changes in 
vital signs, electrocardiogram 
(ECG), and laboratory tests.
#
Incidence of severity grades in 
skin tolerability at times 
indicated in SoA.
#
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
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2.1.1. Primary Estimand(s)
The primary estimands of this study will use the treatment policy strategy and estimate the treatment difference without the benefit of 
additional prohibited medications during treatment and regardless of participant compliance with the IP dosing. This estimand 
(Estimand 1) for AD and Psoriasis are defined according to the primary objectives and are in alignment with the primary endpoints. 
For AD, it includes the following 4 attributes:
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#
Population: Participants with mild or moderate AD as defined by the inclusion and exclusion criteria; without the benefit of 
receiving prohibited medications during treatment and regardless of compliance.  
#
Variable: Percent change from baseline in EASI total score at Week 6.
#
Intercurrent event(s): A) Prohibited medication – all scores in participants who receive prohibited medication post 
randomization will be omitted from the analysis and treated as missing scores.  Missing scores will be imputed based on the 
assumption that participants do not benefit from the IP treatment. B) Withdrawal and all other events leading to missing data 
will be treated similarly assuming participants have efficacy values similar to control participants. C) Inadequate compliance –
participants data will be used as recorded.
#
Population-level summary: The percent change from baseline mean difference between treated and vehicle in EASI score.
For Psoriasis, it includes:
#
Population: Patients with mild to moderate plaque psoriasis as defined by the inclusion and exclusion criteria of the study who 
do not take prohibited medications during treatment and regardless of compliance.
#
Variable: Change from baseline PASI score at Week 6.
#
Intercurrent events: A) Prohibited medication – all scores in participants who receive prohibited medication post 
randomization will be omitted from the analysis and treated as missing scores.  Missing scores will be imputed based on the 
assumption that participants do not benefit from the IP treatment.  B) Withdrawal and all other events leading to missing data 
will be treated similarly as in A).  C) Inadequate compliance – participants data will be used as recorded.
#
Population-level summary: The mean difference between treated and vehicle control arms of the change from baseline PASI 
score. 
2.1.2. Secondary Estimand(s)
Estimand E2: This estimand is intended to provide a population level estimate of the treatment effect of the IP on a binary responder 
endpoint; without the benefit of additional prohibited medications and regardless of a participant compliance with the IP dosing.
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All continuous secondary endpoints will be analyzed descriptively and using estimand E1 described above, when appropriate.
All binary secondary endpoints will be analyzed descriptively and using estimand E2 described above, when appropriate.
#
Population: Participants with mild or moderate AD or Psoriasis as defined by the inclusion and exclusion criteria; without the 
benefit of receiving prohibited medications during treatment and regardless of compliance.
#
Variables: Proportion of participants achieving IGA score of clear (0) or almost clear (1) and a reduction from baseline of 
≥2 points at Week 6 for AD; Proportion of participants with PGA score clear (0) or almost clear (1) (on a 5-point scale) and 
≥2 points improvement from baseline at Week 6 for Psoriasis; and other categorical secondary endpoints.
#
Inter-current Events: A) Prohibited medication – response will be considered negative for participants who receive prohibited 
medication post-randomization. B) Withdrawal and all other events leading to missing data will be treated similarly assuming 
that participants no longer receive benefit from the IP and hence will be treated as failure for endpoint above. C) Inadequate 
compliance – participants data will be used as recorded.
#
Population level summary: 
The difference in proportions between IP treated and vehicle response rates.
2.1.3. Additional Estimand(s)
There is no defined estimand for other endpoints, and they will be analyzed using Pfizer data standards as applicable.
2.2. Study Design
This is a phase 2a, randomized, double blind, vehicle controlled, parallel group, multicenter study on the efficacy, safety, tolerability 
and PK of PF-07038124 0.01% QD versus vehicle control in the treatment of adult participants with mild to moderate AD or mild to 
moderate plaque psoriasis.  In this study the efficacy of PF-07038124 ointment versus vehicle will be assessed in two different 
indications – there is a separate vehicle control group for each indication.
A total of approximately 88 participants with AD or psoriasis will be randomly assigned to study intervention in this basket trial 
design. 
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For AD, a maximum of approximately 56 participants will be randomly assigned to study intervention such that approximately 42 
evaluable participants complete the study.  Assuming a 25% drop out rate, approximately 28 participants will be randomized to either 
PF-07038124 or vehicle control to achieve approximately 21 completers in each group.  Randomization will be stratified by baseline 
disease severity (mild [Investigator's Global Assessment or IGA = 2] vs. moderate [IGA = 3]).  Up to 25% of AD participants will 
have an IGA score of 2 at baseline. 
For psoriasis, a maximum of approximately 32 participants will be randomly assigned to study intervention such that approximately
24 evaluable participants complete the study.  Assuming a 25% drop out rate, approximately 16 participants will be randomized to 
PF-07038124 or vehicle control to achieve 12 completers in each group.  Randomization will be stratified by baseline disease severity 
(mild [Physician Global Assessment or PGA = 2] vs. moderate [PGA = 3]).  Up to 25% of participants will have a PGA score of 2 at 
baseline. 
The total duration of study participation will be approximately 17 weeks, including a screening period of up to 6 weeks, a double-
blind, placebo-controlled treatment period of 6 weeks, and a safety follow-up period of 4-5 weeks from last dose of study drug to last 
study visit.  The study intervention arms and duration for AD and psoriasis participants are the same.
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Figure 1 Study Design Schema 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND CONVENTIONS
3.1. Primary Endpoint(s)
#
Percent change from baseline in EASI total score at Week 6 (see Protocol Section 3.1). The baseline will be defined as the 
EASI total score on Day 1 predose.
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#
Change from baseline in PASI score at Week 6 (see Protocol Section 3.2). The baseline will be defined as PASI score on Day 1
predose.
3.2. Secondary Endpoint(s)
For AD:
#
Proportion of participants achieving IGA score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from 
baseline of ≥2 points at Week 6 and other study visit time points specified in the SoA.
#
Proportion of participants achieving EASI 75 (75% improvement from baseline) at study visit time points specified in the SoA.
#
Proportion of participants having ≥4 points of reduction in weekly averages of Peak Pruritus Numerical Rating Scale 
(PP-NRS) from baseline at study visit time points specified in the SoA.
#
Change from baseline in EASI total score at study visit time points specified in the SoA.
#
Proportion of participants achieving IGA score of clear (0) or almost clear (1) at study visit time points specified in the SoA.
#
Percent change from baseline in affected Body Surface Area (BSA) at study visit time points specified in the SoA.
#
Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs), clinically significant changes in vital 
signs, electrocardiogram (ECG), and laboratory tests.
#
Incidence of severity grades in skin tolerability at times indicated in SoA.
For Psoriasis:
#
Proportion of participants with PGA score clear (0) or almost clear (1) (on a 5-point scale) and ≥2 points improvement from 
baseline at Week 6 and other study visit time points specified in the SoA.
#
Proportion of participants achieving PASI 75 (75% or greater improvement from baseline) at study visit time points specified 
in the SoA.
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#
Proportion of participants who achieved a Psoriasis Symptoms Inventory (PSI) score of 0 (not at all) or 1 (mild) on every item 
at study visit time points specified in the SoA.
#
Change from baseline in PASI scores at study visit time points specified in the SoA (except Week 6). 
#
Percent change from baseline in PASI scores at study visit time points specified in the SoA. 
#
Proportion of participants with PGA score clear (0) or almost clear (1) and ≥2 points improvement from baseline at time 
points specified in the SoA.
#
Percent change from baseline in BSA at study visit time points specified in the SoA.
#
Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs), clinically significant changes in vital 
signs, electrocardiogram (ECG), and laboratory tests.
#
Incidence of severity grades in skin tolerability at times indicated in SoA.
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3.4. Baseline Variables
In general, for all analyses, baseline will be defined based on observations collected prior to first dose. Baseline values for 
demographics and hight will be based on measures collected at Visit 1/Screening visit.  Study Day 1 is defined as the day the subject 
receives first dose of study drug.  For purposes of all other analyses including analyses for change from baseline, the baseline value 
will be defined as the last measurement before first dose on Day 1.  If a value is missing on Day 1, then the last available observation 
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before Day 1 will be used.  For the PP-NRS score, baseline will be defined as the average of all values recorded between Day -7 and 
Day -1.  
3.5. Safety Endpoints
Safety will be assessed by the spontaneous reporting of AEs, physical examinations, and clinical laboratory results in all subjects who 
receive at least one dose of the investigational product.  Unscheduled safety assessments may be performed at any time during the 
study to assess any perceived safety concerns.  Endpoints will be assessed as:
#
Incidence of treatment emergent adverse events.
#
Incidence of SAEs and AEs leading to discontinuation.
#
Incidence of clinical abnormalities and change from baseline in selected clinical laboratory values, ECG measurements, and 
vital signs.
The safety endpoints will be defined in accordance with Clinical Data Interchange Standards Consortium (CDISC) and Pfizer 
Standards (CaPS).
3.5.1. Adverse Events
An adverse event will be considered a Treatment-Emergent Adverse Event (TEAE) if the event started during the effective duration of 
treatment.  All events that start on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag 
time will be flagged as TEAEs.  The algorithm will not consider any events that started prior to the first dose date.
3.5.2. Laboratory Data
The laboratory tests will be performed at time points identified in the Schedule of Activities. Unscheduled clinical labs may be 
obtained at any time during the study to assess any perceived safety concerns at the investigator’s discretion.
3.5.3. Vital Sign
Vital signs (blood pressure, pulse, and oral or tympanic temperature) will be measured after a minimum of 5 minutes rest as indicated 
in the Schedule of Activities.   
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3.5.4. Electrocardiograms
Single 12-lead ECGs should be collected at times specified in the Schedule of Activities.
The baseline ECG values (the last measurement prior to receive study treatment on  Day 1) will serve as each subject’s baseline 
values.   
Only categorical summaries of the ECG data according to sponsor data standard will be provided.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in each analysis population prior to 
releasing the database and classifications will be documented per standard operating procedures.
Population 
Description
Modified Intention to Treat (mITT) or 
Full Analysis Set (FAS)
All participants randomly assigned to IP and who apply at least 1 dose of IP.  
Safety Analysis Set
All participants randomly assigned to IP and who apply at least 1 dose of IP.  
Participants will be analyzed according to the product they actually have received.
5. GENERAL METHODOLOGY AND CONVENTIONS
The primary analysis will be performed when all randomized subjects have either completed their 6-week study participation period 
or withdrawn early or should the study be stopped prematurely due to any reason, and the database is released.  
5.1. Hypotheses and Decision Rules
Statistical inference will be made on the primary endpoints: (percentage change from baseline in EASI score at Week 6 and change 
from baseline in PASI score at Week 6). The null hypothesis is that there is no difference PF-07038124 its corresponding vehicle arm 
(ie, AD vehicle and Psoriasis vehicle). The alternative hypothesis is that the PF-07038124 arm being tested is superior to its 
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corresponding vehicle at Week 6 in AD and/or Psoriasis patients. The study will be considered positive for AD and/or Psoriasis, if 
either one or both null hypotheses are rejected.
The sample size calculation is based on the primary endpoint (percentage change from baseline in EASI score at Week 6).  A total of 
56 randomized participants in 1 treatment group and 1 vehicle group (28/arm) will provide approximately 90% power to detect a 
difference of 50 in percentage change from baseline with a common standard deviation 48% between PF-07038124 and a vehicle 
arm, controlling the two-sided error rate alpha 0.05.  These calculations allow for a 25% dropout rate leaving 42 evaluable 
participants (21/arm).
For the key secondary endpoint, IGA response rate of clear or almost clear and ≥2 points improvement at Week 6, assuming 20% rate 
for vehicle and 55% rate for the treatment, this sample size provides 66% power controlling the two-sided error rate alpha 0.05.
The sample size is based on the primary efficacy endpoint, PASI change from baseline at Week 6.  With an assumed standard 
deviation of 4.2 and treatment difference of 4.5, a total of 32 randomized participants in 2 treatment groups (16/arm) will provide 
approximately 80% power for the comparison of active versus vehicle group at a two-sided significance of 0.1.  This calculation 
allows for an approximate 25% dropout rate, that is 12 participants evaluable per arm at Week 6, where evaluable is defined as 
included in the mITT set.
For the key secondary endpoint, PGA response rate of clear or almost clear and ≥2 points improvement at Week 6, assuming 20%
rate for vehicle and 65% rate for the treatment, this sample size provides 61.9% power controlling the two-sided error rate alpha 
0.05.
5.2. General Methods
5.2.1. Analyses for Binary Endpoints
Landmark (cross-sectional) analyses of key binary endpoints will be analyzed by first treating missing data as non-responders and then 
applying Chan and Zhang’s exact confidence interval (CI) method1.
For all binary endpoints, a summary based on the mITT of the number of subjects in each category based on observed cases in each 
treatment arm at each time point will be produced and the response rate will also be plotted against time, by treatment group.  
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5.2.2. Analyses for Continuous Endpoints
Landmark (cross-sectional) analysis of key continuous endpoints will use analysis of covariance (ANCOVA). The ANCOVA model 
will include terms for treatment arm and baseline score of the dependent variable. Least-squares means at the mean overall baseline 
score will be presented along with 90% confidence intervals.
Mixed model repeated measures (MMRM) models will be used.  The fixed effects of treatment, visit, and treatment by visit 
interaction will be included.  Visit will be modeled as a categorical covariate.  Unstructured covariance matrix will be assumed for the 
model errors. Compound symmetry covariance matrix will be used if the model with unstructured covariance doesn’t converge.
When modeling the change from baseline values, the variable for visit will start with the first post-baseline visit, and the actual 
baseline value will be included as a covariate.  At each visit, estimates of least square mean (LSM) values and the LSM differences 
between the PF-07038124 treated group and the corresponding vehicle group will be derived from the model for AD and Psoriasis 
patients separately. The corresponding p-values and 90% confidence intervals will also be derived from the model.
Unless stated otherwise, descriptive summary statistics for all continuous variables will be presented on mITT observed data by 
treatment group and will include n, mean, median, standard deviation, minimum and maximum.
5.2.3. Analyses for Categorical Endpoints
NA.
5.2.4. Analyses for Time-to-Event Endpoints
NA.
5.3. Methods to Manage Missing Data
5.3.1. Efficacy Data
The primary analysis will use the primary estimand continuous endpoint set.  For each landmark analysis (eg, cross sectional analysis 
by week) missing data, except missing due to COVID-19 pandemic, will be imputed using a control based imputation method.  PROC 
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MI will first be called at the visit and a control based method (implemented with the MNAR option) will impute missing vehicle 
observations under the assumption data are missing at random (MAR) and impute missing treatment observations assuming they are 
similar to corresponding vehicle patients.  
Summaries of continuous data will use the observed data only and no additional considerations are needed.
Analysis of binary data will use the Secondary Estimand Categorical Endpoint Set.  This dataset by definition has no missing data 
since all missing values, except missing due to COVID-19 pandemic, will have been set to a non-responder.  Summaries will use the 
Observed Efficacy Set and will report results on an observed case (OC) basis. 
If a subject misses a visit due to COVID-19, he/she will be excluded from the analysis for that visit; If a subject discontinues treatment 
or withdraws from the study due to COVID-19, he/she will be excluded from the analyses after the treatment discontinuation visit or 
study withdrawal visit, respectively.  
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6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
6.1.1. Percentage Change from Baseline in EASI Score at Week 6 & Change from Baseline PASI Score at Week 6
6.1.1.1. Main Analysis
#
Estimand strategy: Primary Estimand (Section 2.1.1). This estimand is intended to provide an estimate of the treatment effect 
in the absence of prohibited medication use in a population that may or may not be fully compliant with the treatment.
#
Analysis set: mITT (Section 4) using data prepared in the description of the full analysis set.
#
Analysis methodology: Percent change from baseline will be analyzed using an ANCOVA with the observed (or imputed) 
Week 6 change from baseline EASI score as the dependent variable with treatment arm and baseline EASI score as the 
independent variables. Same method will be used for change from baseline PASI score at Week 6. 
#
Intercurrent events and missing data: Data prohibited medication will be excluded and set to missing. Missing data which will 
be multiply imputed using a control-based strategy as described in (Section 5.3). A thousand (1000) imputed datasets will be 
used in the analysis and results combined using PROC MIANALYZE.
#
The least-squares (LS) means, the 90% confidence interval for the LS means, the difference between the LS means for each 
pair of treatment groups, and the corresponding 90% confidence interval will be presented.
6.1.1.2. Sensitivity/Supplementary Analyses
Sensitivity Analyses:
#
To assess the impact of baseline distribution, the main analysis will be repeated with the ANCOVA model replaced by an 
ANOVA model (excluding baseline as a covariate).
Supplementary Analyses:
#
Mixed model repeated measures (MMRM) models will be used (assuming missing data are missing at random). The fixed 
effects of treatment, visit, and treatment by visit interaction will be included. Visit will be modeled as a categorical covariate. 
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6.2. Secondary Endpoint(s)
6.2.1. IGA/PGA Responses at Week 6
6.2.1.1. Main Analysis
#
Estimand strategy: Secondary estimand (Section 2.1.2) use a composite endpoint strategy. This estimand is intended to provide 
an estimate of the treatment effect in the absence of prohibited medication use in a population that may or may not be fully 
compliant with the treatment.
#
Analysis set: mITT (Section 4) using data prepared in the description of the Secondary Estimand Categorical Endpoint Set.
#
Analysis methodology: Risk differences will be analyzed using the method of Chan and Zhang (1999). Confidence Interval of 
binomial proportion will be reported using Blyth-Still-Casella method. 
#
Intercurrent events and missing data: These have been accounted for in the preparation of the Secondary Estimand Categorical 
Endpoint Set (Section 5.3).  This prepared data set has no missing values.
#
Proportions, risk differences and 90% confidence intervals will be presented.  
6.2.2. Other Binary Secondary Endpoints
EASI 75, PP-NRS response Rate, IGA of clear or almost clear, PASI 75, PGA of clear or almost clear andPSI response rate will be 
analyzed the same way as described in Section 6.2.1.
6.2.3. Other Continuous Secondary Endpoints
Change from baseline EASI, Percent change from baseline in affected BSA (in AD patients), Change from baseline PASI (except 
Week 6), Percent change from baseline PASI, Percent change from baseline in affected BSA (in Psoriasis patients)
6.2.3.1. Main Analysis   
#
Estimand strategy: Primary Estimand (Section 2.1.1). This estimand is intended to provide an estimate of the treatment effect 
in the absence of prohibited medication use in a population that may or may not be fully compliant with the treatment.
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#
Analysis set: mITT (Section 4) using data prepared in the description of the Primary Estimand Continuous Endpoint Set.
#
Analysis methodology: Percent and absolute change from baseline at week 6 will be analyzed using an ANCOVA with the 
observed endpoint data as the dependent variable with treatment arm and baseline endpoint value as the independent variables. 
#
Intercurrent events and missing data: Data prohibited medication will be excluded and set to missing. For ANCOVA analysis
at week 6, missing data which will be multiply imputed using a control-based strategy as described in (Section 5.3). A 
thousand (1000) imputed datasets will be used in the analysis and results combined using PROC MIANALYZE.
#
The least-squares (LS) means, the 90% confidence interval for the LS means, the difference between the LS means for each 
pair of treatment groups, and the corresponding 90% confidence interval will be presented.
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6.5. Subset Analyses
There are no subset analyses are planned.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Baseline Summaries
Demographic and baseline characteristics will be summarized by randomized treatment group for all randomized and treated subjects. 
Continuous variables will be summarized using mean and standard deviation. Categorical variables will be summarized using relative 
frequency. Key demographic and baseline variables to be summarized include: geographic region, age, gender, race, ethnicity, height, 
weight, body mass index, disease duration, baseline EASI score, baseline IGA, baseline PASI score, baseline PGA, baseline BSA 
score etc.
6.6.2. Study Conduct and Participant Disposition
Subjects’ evaluation, disposition and discontinuation will be summarized according to CaPS.
6.6.3. Study Treatment Exposure
A summary of dosing compliance by treatment group will be provided.
The exposure to study drug will be summarized by the total number of days of dosing, mean/median number of days of exposure and 
number and percent of subjects in exposure duration categories.
6.6.4. Concomitant Medications and Nondrug Treatments
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be summarized according to CaPS.
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6.7. Safety Summaries and Analyses
The analysis population for safety is described in Section 4. Safety and tolerability will be assessed by clinical review of all relevant 
parameters including adverse experiences (AEs) and laboratory tests.  A complete list of laboratory parameters can be obtained in 
Section 8.2.5 of the protocol. 
All the tables, listings and graphs for adverse events, lab parameters and vital sign and ECG will follow Pfizer standards. The binary 
safety endpoints including the incidences of on-treatment AEs, withdrawals due to AEs and serious AEs will be analyzed using the 
exact test described in Section 5.2.1.
6.7.1. Adverse Events
All the tables, listings and graphs for adverse events, lab parameters and vital sign and ECG will follow Pfizer standards. The binary 
safety endpoints including the incidences of on-treatment AEs, withdrawals due to AEs and serious AEs will be analyzed using the 
exact test described in Section 5.2.1.   
There will be no adjustment for multiple comparisons or stratification factors in the analyses unless specified. AEs will be arranged in 
the output sorted in descending point estimate of the risk difference within system organ class.  Footnotes in the outputs will include 
the methods used to derive any p-values and confidence intervals as per Pfizer standards.
It should be recognized that most studies are not designed to reliably demonstrate a causal relationship between the use of a
pharmaceutical product and an adverse event or a group of adverse events. Except for select events in unique situations, studies do not 
employ formal adjudication procedures for the purpose of event classification. As such, safety analysis is generally considered as an 
exploratory analysis and its purpose is to generate hypotheses for further investigation.
6.7.2. Laboratory Data
Laboratory data will be listed and summarized in accordance with the CaPS reporting standards.  Summaries of subjects meeting 
pre-specified monitoring and discontinuation criteria will be created using methods for categorical data.
6.7.3. Vital Signs
Vital signs will be summarized at baseline, Weeks 2, 4, and 6/End of Treatment visits.
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6.7.4. Electrocardiograms
Categorical summary tables will be summarized by treatment and time post-dose using sponsor reporting standards. Baseline is as 
defined in Section 3.5.4. A listing of ECG comments on findings and normal/abnormal results will be provided.
6.7.5. Physical Examination
Physical examinations will be summarized at baseline and all-available post-baseline visits.
7. INTERIM ANALYSES
No interim analyses are planned.
8. REFERENCES
1.
Chan ISF and Zhang Z. Test based exact confidence intervals for the difference of two binomial proportions. Biometrics, 1999, 
55:1201–1209.
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9. APPENDICES
Appendix 1. Summary of Efficacy Analyses
Efficacy Endpoint
Analysis Type
Population
Data Inclusion 
and Rules for 
Handling 
Intercurrent 
Events and 
Missing Data 
Analysis 
Model
Week 6 PCFBL in 
EASI / CFBL in PASI
Primary Analysis
FAS
MI
ANCOVA
PCFBL in EASI / 
CFBL in PASI
Sensitivity Analysis
FAS
OC
MMRM
Week 6 IGA / PGA 
Response
Secondary Analysis
FAS
NRI
Chan & Zhang
Week 6 CFBL in 
EASI / PCFBL in 
PASI / PCFBL in 
BSA
Secondary Analysis
FAS
MI
ANCOVA
EASI 75 / PP-NRS 
Rate / IGA of clear or 
almost clear / PASI 75 
/ PGA of clear or 
almost clear
Secondary Analysis
FAS
NRI
Chan & Zhang
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PCFBL= Percent change from baseline; CFBL= Change from baseline; ANCOVA = Analysis of Covariance; NRI = Non Responder Imputation; OC = Observed 
Cases.
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Appendix 2. Data Derivation Details
Appendix 2.1. Definition and Use of Visit Windows in Reporting
Visit windows will be used for efficacy variables, and for any safety data that display or summarize by study visit.  For other 
endpoints (e.g., ECG, vital signs), visit windows will be applied for summary statistics by study visits if required.
Visit 
No.
Visit Label 
Target Day
Visit Window 
Screening 
N/A
-42 ≤ day ≤-1
1
Baseline*
1 
day = 1
2
Week 1
8
2≤day≤11
3
Week 2
15 
12≤day≤18
4
Week 3
22
19≤day≤25
5
Week 4
29 
26≤day≤36
6
Week 6
43
37≤day≤57
7
FUP/EOS
N/A
day ≥58
* Baseline analysis visit window may be considered as day≤1 in some analyses (eg, those involving change 
from baseline).  That is, in case that Day 1 observation is missing, the last observation before the first dosing 
date may be considered as the baseline.  The baseline measurements for demography, height, pre-study 
medical history and medications will be collected at the “Screening” visit.
If two or more visits fall into the same window, keep the one closest to the Target Day.  If two visits are equally distant from the 
Target Day in absolute value, the later visit should be used.
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Appendix 3. Endpoint Derivations
Eczema Area and Severity Index (EASI)
The EASI quantifies the severity of a subject’s atopic dermatitis based on both severity of lesion clinical signs and the percent of BSA 
affected.  EASI is a composite scoring by the atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, 
excoriation, and lichenification (each scored separately) for each of four body regions, with adjustment for the percent of BSA 
involved for each body region and for the proportion of the body region to the whole body.
Lesion Severity by Clinical Signs: The basic characteristics of atopic dermatitis lesions-erythema, induration/papulation, excoriation, 
and lichenification-provide a means for assessing the severity of lesions.  Assessment of these four main clinical signs is performed 
separately for four body regions: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks).  
Average erythema, induration/papulation, excoriation, and lichenification are scored for each body region according to a 4-point scale: 
0=absent; 1=mild; 2=moderate; 3=severe.  Morphologic descriptors for each clinical sign severity score are shown in the table below.
Clinical Sign Severity Scoring Criteria for the EASI
Score
Description*
Erythema (E)
0
Absent
None; may have residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation).
1
Mild
Light pink to light red
2
Moderate
Red
3
Severe
Deep, dark red
Induration/Papulation (I)
0
Absent
None
1
Mild
Barely palpable to slight, but definite hard thickened skin and/or papules
2
Moderate
Easily palpable moderate hard thickened skin and/or papules
3
Severe
Severe hard thickened skin and/or papules
Excoriation (Ex)
0
Absent
None
1
Mild
Slight, but definite linear or picked scratch marks or penetrating surface injury
2
Moderate
Moderate linear or picked scratch marks or penetrating surface injury
3
Severe
Severe linear or picked scratch marks or penetrating surface injury
Lichenification (L)
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0
Absent
None
1
Mild
Barely perceptible to slight, but definite thickened skin, fine skin markings, and lichenoid scale
2
Moderate
Moderate thickened skin, coarse skin markings, and coarse lichenoid scale
3
Severe
Severe thickened skin with very coarse skin markings and lichenoid scale
∃The EASI will exclude scalp, palms, and soles from the assessment/scoring.
%BSA with Atopic Dermatitis: The number of handprints of skin afflicted with atopic dermatitis in a body region can be used to 
determine the extent (%) to which a body region is involved with atopic dermatitis (see table below).  When measuring, the handprint 
unit refers to the size of each individual subject’s hand with fingers in a closed position.
Handprint Determination of %BSA
Body Region
Total Number of Handprints in 
Body Region*
Surface Area of Body Region 
Equivalent of One Handprint*
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae and groin/genitals)
30
3.33%
Lower Limbs (including buttocks)
40
2.5%
Handprint refers to the hand size of each individual subject.
* The number of handprints will be for the entire body region; these values will not be adjusted for exclusion of scalp, palms, and soles from the BSA 
assessment.
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
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Body Region Weighting: Each body region is weighted according to its approximate percentage of the whole body (see table below).
EASI Body Region Weighting
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and 
groin/genitals)
0.3
Lower Limbs (including buttocks)
0.4
* No adjustment for body regions excluded for assessment.
In each body region, the sum of the Clinical Signs Severity Scores for erythema, induration/papulation, excoriation, and 
lichenification is multiplied by the Area Score and by the Body Region Weighting to provide a body region value, which is then 
summed across all four body regions resulting in an EASI score as described in Equation below.
EASI =
0.1Ah(Eh+Ih+Exh+Lh) + 0.2Au(Eu+Iu+ExU+Lu) + 0.3At(Et+It+Ext+Lt) + 0.4Al(El+Il+Exl+Ll)
A = Area Score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t 
= trunk; l = lower limbs.
The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of atopic 
dermatitis.
Investigator’s Global Assessment (IGA)
The Investigator’s Global Assessment of atopic dermatitis is scored on a 5-point scale (0-4), reflecting a global consideration of the 
erythema, induration and scaling.  The clinical evaluator of atopic dermatitis will perform an assessment of the overall severity of 
atopic dermatitis and assign an IGA score and category as described in the table below.  The assessment will be a static evaluation 
without regard to the score at a previous visit.
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IGA Score
Score
Category
Description∃
0
Clear
Atopic dermatitis is cleared, except for any residual discoloration (post-inflammatory hyperpigmentation 
and/or hypopigmentation).
1
Almost Clear
Overall, the atopic dermatitis is not entirely cleared and remaining lesions are light pink (not including post 
inflammatory hyperpigmentation) and/or; have barely palpable hard thickened skin and/or papules and/or; 
have barely perceptible lichenification; excoriation and oozing/crusting are absent.
2
Mild
Overall, the atopic dermatitis consists of lesions that are light red; with slight, but definite hard thickened 
skin and/or papules; with slight, but definite linear or picked scratch marks or penetrating surface injury; 
with slight, but definite thickened skin, fine skin markings, and lichenoid scale; oozing/crusting is absent.
3
Moderate
Overall, the atopic dermatitis consists of lesions that are red; with easily palpable moderate hard thickened 
skin and/or papules; with moderate linear or picked scratch marks or penetrating surface injury; with 
moderate thickened skin, coarse skin markings, and coarse lichenoid scale; with slight oozing/crusting.
4
Severe
Overall, the atopic dermatitis consists of lesions that are deep, dark red; with severe hard thickened skin 
and/or papules; with severe linear or picked scratch marks or penetrating surface injury; with severe 
thickened skin with very coarse skin markings and lichenoid scale; with moderate to severe oozing/crusting.
∃The IGA will exclude scalp, palms, and soles from the assessment/scoring.
Peak Pruritis Numerical Severity Scale (PP-NRS)
On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how would you rate your itch at the worst moment 
during the previous 24 hours?
10
9
8
7
6
5
4
3
2
1
0
10
9
8
7
6
5
4
3
2
1
0
No 
itch
Worst 
itch 
imaginable
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Psoriasis Area Severity Index (PASI)
The Psoriasis Area and Severity Index quantifies the severity of a subject's psoriasis based on both lesion severity and the percentage 
of body surface area affected. Lesion severity: the basic characteristics of psoriatic lesions - erythema, induration and scaling -
provide a means for assessing the severity of lesions. Assessment of these three main signs is performed separately for four areas of 
the body: head, upper limbs, trunk, and lower limbs. Average erythema, induration and scaling are rated for each body area according 
to a 5-point scale: 0, no involvement; 1, slight; 2, moderate; 3, marked; 4, very marked.
Body surface area (BSA) involvement: the extent (%) to which each of the four areas of the body is affected by psoriasis is assigned a 
numerical score according to the following area scoring criteria: 0, no involvement; 1, >0 to 9%; 2, 10 to 29%; 3, 30 to 49%; 4, 50 to 
69%; 5, 70 to 89%; 6, 90 to 100%. Details see Table 5 of the protocol.
Derivation of PASI score
In each area, the sum of the severity rating scores for erythema, induration and scaling is multiplied by the score representing the 
percentage of this area involved by psoriasis, multiplied by a weighting factor (head 0.1; upper limbs 0.2; trunk 0.3; lower limbs 0.4). 
The sum of the numbers obtained for each of the four body areas is the PASI.
PASI = 0Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl)
where A = area of involvement score; E = erythema; I =induration; S = scaling; h = head; 
u = upper limbs; t = trunk; l = lower limbs
The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis.
PASI 
/75/
response
At least 
/75/
% reduction in PASI relative to baseline PASI Score.
Body Surface Area (BSA)
Assessment of body surface area involved in psoriasis is performed separately for four areas of the body: head, upper limbs, trunk, and 
lower limbs. The percentage surface area affected by psoriasis is estimated by means of the "handprint method", where the full hand 
of the subject (ie, the subject's flat hand, thumb and fingers) represents approximately 1% of the total BSA2 and a set percentage of 
each of the four areas of the body:
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#
1 handprint corresponds to approximately 10% of the head/neck;
#
1 handprint corresponds to approximately 5% of the arm/upper limbs;
#
1 handprint corresponds to approximately 3.3% of the trunk;
#
1 handprint corresponds to approximately 2.5% of the lower limbs.
The extent (%) to which each of the four areas of the body is affected is captured on the CRF (to 2 decimal places, as necessary). A 
weighting factor is applied to each of the four areas in calculation of the total body surface area affected: head x0.1; upper limbs x0.2; 
trunk x0.3; lower limbs x0.4, as the four areas correspond to approximately 10%, 20%, 30% and 40% of the total BSA, respectively. 
The sum of the weighted percent involvement obtained for each of the four body areas is the overall psoriatic BSA.
Handprint Determination of %BSA
Body Region
Total Number of Handprints in 
Body Region*
Surface Area of Body Region 
Equivalent of One Handprint*
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae and groin/genitals)
30
3.33%
Lower Limbs (including buttocks)
40
2.5%
Handprint refers to the hand size of each individual subject.
* The number of handprints will be for the entire body region; these values will not be adjusted for exclusion of scalp, palms, and soles from the BSA 
assessment.
Physician Global Assessment (PGA)
The Physician Global Assessment of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, 
induration and scaling across all psoriatic lesions. Average erythema, induration and scaling are rated separately over the whole body 
according to a 5-point severity scale, scored from 0 to 4, with appropriate morphologic descriptors. The severity rating scores are 
summed and the average taken - the total average is rounded to the nearest whole number score to determine the PGA. The 5-point 
scale for PGA is: 0, "clear"; 1, "almost clear"; 2, "mild"; 3, "moderate"; 4 "severe".
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Details on C-SSRS Mapping
Columbia-Classification Algorithm of Suicide Assessment (C-CASA)
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Appendix 4. Sample SAS Code for Estimand 1 
libname c3941002  "/Volumes/app/…… /data_vai" ;
data ps;
              set c3941002.adps;
run;
data look;
              set ps;
              where param = "EASI02-Total Sum"  and viswin ne .;
              keep subjid param paramn avisit age sex trta viswin visit xviswin aval base chg pchg trtan;
run;
**example data for a single visit;
**created from systemic study ;
**ignore values, only used for illustration;
**data already has one record per subject per visit even if
**data is missing. Proc Mi needs missing values in order to impute;
data ex1;
              set look;
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              where upcase(avisit)=’WEEK 6’;
regimen = "QD";
if trtan = 1 then dose=0;
if trtan = 2 then dose=0.01;
              keep subjid dose regimen chg aval base;
run;
proc means data=ex1;
              class regimen dose;
              var chg aval;
run;
proc sort data=ex1 out=ex2;
    *data must be sorted by regimen before usin proc mi;
              by regimen dose;
run;
*imputing aval=observed so range of endpoint 0-72 can be included in;
*mi procedure;
proc mi data=ex2 seed=1022 nimpute=1000 out=outimp  max=72 min=0;
              by regimen;
              class dose;
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              monotone reg(aval= base/details);
              mnar model( aval/modelobs = (dose="0"));
              var base   aval;
run;
proc univariate data=outimp;
var aval;
histogram ;
run;
data outimp1;
              set outimp;
              chg = aval - base;**calculate chg from baseline
run;
proc sort data = outimp1 out = outimp2;
    by _imputation_ regimen dose subjid;
run;
              
proc mixed data=outimp2;
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             by _imputation_;
             class dose regimen;
             model chg = base dose*regimen;
             lsmeans dose*regimen/ diff alpha=.1 ;
             ods output diffs=diffs lsmeans=lsmeans;
run;
              
data diffsout;
              set diffs;
              **only keep within regimen contrasts vs placebo;
              where regimen = _regimen and dose = 0;
run;
**now use mianalyze on lsmean differences;
**First sort by group, regimen and _dose (dose = 0 for all groups);
proc sort data=diffsout out=diffsout1;
              by regimen _dose _imputation_;
run;
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**now mianalyze by regimen and _dose;
**NB mianalyze only uses estimates and standard errors not CI limits etc.;
proc mianalyze data=diffsout1  alpha=.1;  **specify alpha for 90% CIs here;
      by regimen _dose;
      modeleffects estimate;
      stderr stderr;
      ods output parameterestimates=parameterestimates;
run;
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Appendix 5. Sample SAS Code for Estimand 2 – Risk Difference using Chan and Zhang (1999)
PROC BINOMIAL DATA=<DATASET> GAMMA=0 ALPHA=<Value>;
PD/EX ONE STD;
PO <POPULATION VARIABLE>;
OU <OUTCOME VARIABLE>;
RUN;
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Appendix 6. Sample SAS Code for the Confidence Interval of a Binomial Proportion (Blyth-Still-Casella)
PROC BINOMIAL DATA=<DATASET> ALPHA=<value>;
BI/BS;
OU <RESPONSE VARIABLE>;
RUN;
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Appendix 7. Sample SAS Code for MMRM
proc mixed data=_dsnin order=internal alpha=0.1;
    by PARAMN;
    class SUBJID AVISITN TRTPN;
    model PCHG = BASE TRTPN AVISITN  TRTPN*AVISITN /solution ddfm=kr;
    repeated AVISITN/ subject =SUBJID type=un r rcorr; /**try UN first, if not converged, will use CS***/
    lsmeans TRTPN*AVISITN / diff cl alpha=0.1; 
    ods output lsmeans=lsmeans diffs=diffs;
run;
/*For one-sided P-value calculation, the LOWER tail side should be used. */;
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Appendix 8. List of Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AA
alopecia areata
Ab
antibody
Abs
absolute
AD
atopic dermatitis
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BCG
bacille Calmette-Guerin
%-hCG
beta-human chorionic gonadotropin
BID
twice daily
BMI
body mass index
BP
blood pressure
BSA
body surface area
BUN
blood urea nitrogen
CAT
computerized axial tomography
CD
Crohn’s disease
CFR
Code of Federal Regulations
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Abbreviation
Term
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CLIA
Clinical Laboratory Improvement Amendments
CMV
Cytomegalovirus
CO2
carbon dioxide (bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRO
contract research organization
CSR
clinical study report
C-SSRS
Columbia suicide severity rating scale
CT
clinical trial
DILI
drug-induced liver injury
DU
dispensable unit
EASI
Eczema Area and Severity Index
EBV
Epstein Barr virus
EC50
Half-maximal effective concentration
EC
ethics committee
ECG
Electrocardiogram
eCRF
electronic case report form
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EOS
end of study
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Abbreviation
Term
EOT
end of treatment
ePRO
electronic patient reported outcome
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
F
bioavailibility
FDA
Federal Drug Administration
FSH
follicle-stimulating hormone
Fu
fraction unbound
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAb 
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HBV
hepatitis B visrus
HCVAb
hepatitis C virus antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
hsCRP
high sensitivity C-reactive protein 
IB
investigator’s brochure
IC50
half-maximal inhibitory concentration 
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN-!
Interferon alpha
IGA
Investigator’s Global Assessment 
IgE
immunoglobulin E
IgG
immunoglobulin G
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Abbreviation
Term
IGRA
Interferon Gamma Release Assay
IL-
interleukin
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IP-10
interferon-induced protein 10
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous 
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantification
JAK
Janus Kinase
LDL
low density lipoprotein 
MAD
multiple ascending dose
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
Mg
milligram
MMP12
Matrix metalloproteinase 12
mRNA
messenger ribonucleic acid
MRI
magnetic resonance imaging
Msec
millisecond
MTX
methotrexate
N/A
not applicable
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Abbreviation
Term
NOAEL
no-observed-adverse-effect level
NRS
Numerical Rating Scale
NTIS
Night time itch scale
PASI
Psoriasis area and severity index
PCD
primary completion date
PCP
primary care physician
PCR
polymerase chain reaction 
PD
pharmacodynamic(s)
PG
polypropyle glycol
PI
principal investigator
PK
pharmacokinetic(s)
PPD
Purified Protein Derivative
PP-NRS
Peak Pruritus Numerical Rating Scale
PR
pulse rate
PRO
Patient reported outcomes
PSAAD
Pruritis and Symptoms Assessment for Atopic Dermatitis
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QFT-G
QuantiFERON-TB Gold Test
QFT-GIT
QuantiFERON-TB Gold In-tube Test
QT
Q wave interval
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
Qual
qualitative
QW
once a week
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Abbreviation
Term
RBC
red blood cell
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
S Cystatin C
serum Cystatin C
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SSID
subject study identification n
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBili
total bilirubin
TdP
Torsade de Pointes
TEAE
treatment emergent adverse events
TNF
tumor necrosis factor
TYK2
Tyrosine Kinase 2
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
UVA
ultraviolet A light 
UVB
ultraviolet B light
VZV
varicella zoster virus
WBC
white blood cell
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Abbreviation
Term
WOCBP
woman of childbearing potential
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