Clinical trial NCT04668066
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis inflammatory skin disease
Sponsor: Pfizer
Start date: 2020-12-10; Completion date: 2022-12-27
Enrollment: 121 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is the first time PF-07242813 will be given to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07242813 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms.

Detailed description:

Arms: arm 1: Participants will receive a single intravenous dose of either PF-07242813 or placebo arm 2: Participants will receive multiple subcutaneous doses PF-07242813 or placebo arm 3: Participants will receive a single intravenous dose of either PF-07242813 or placebo
Interventions: intervention 1: PF-07242813 intervention 2: Placebo
Intervention descriptions: intervention 1: PF-07242813 given intravenously or subcutaneous intervention 2: Placebo given intravenously or subcutaneous

Protocol documents:
Prot_000.pdf: 
PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
 
 
A PHASE 1 FIRST IN HUMAN, RANDOMIZED, DOUBLE BLIND, SPONSOR 
OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE 
ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF 
PF-07242813 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH ATOPIC 
DERMATITIS 
 
 
 
 
Study Intervention Number: 
Study Intervention Name: 
US IND Number: 
PF-07242813 
N/A 
148,558 
EudraCT Number: 
N/A 
ClinicalTrials.gov ID: 
NCT04668066 
Protocol Number: 
C4461001 
Phase: 
1 
 
Short Title: A Phase 1 Study to Evaluate the Safety and Tolerability of PF-07242813 in 
Healthy Participants and Participants with Atopic Dermatitis. 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 2 
 
 
Protocol Amendment Summary of Changes Table 
 
Document History 
Document 
Version Date 
Summary and Rationale for Changes 
Amendment 2 
10 July 2021 
1. Schedule of Activities for Multiple Ascending 
Doses (MAD) in Healthy Participants, Table 2: 
Three (3) additional PK samples will be collected 
in MAD cohorts on Days 8, 19 and 
33 respectively. 
Further, decreased the time window for PK 
sample collection has been narrowed, from 
±3 days to ±1 day, for Day 8, Day 22 and Day 36 
visits. These changes were made to better 
characterize the PK profile after subcutaneous 
administration. 
The immunogenicity sample noted for collection 
on Day 8 in MAD cohorts has been removed as it 
was unnecessary. 
2. Section 4.1.1, Section 8.5: 
Flexible language added to allow additional PK 
sample collection and analysis, as needed and 
appropriate, based on emerging data. 
3. Section 5.2. Exclusion Criteria 25.c. and 
Section 8.8.3.5: 
Revised Exclusion Criteria #25 to modify 
hormone test requirements prior to randomization 
such that the laboratory data are evaluated in the 
context of clinical signs of endocrinopathy. 
4. Section 9.1: 
Language updated from mean change to percent 
change from baseline to be consistent with the 
analysis as described in Sections 3 and 9.4.1. 
5. Sections 5.4 and 8: 
Delays in randomization up to 1 week due to 
delayed laboratory test results will not be 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 3 
 
 
 
considered protocol deviations. 
6. Section 8.8.1.1: 
Clarified language regarding processing of skin 
punch biopsies. 
7. Revisions outlined in Protocol Administrative 
Letters (PACLs) #1, dated 26 February 2021 and 
#2, dated 14 June 2021 have been incorporated. 
8. Appendix 4, Section 10.4.4 Contraception 
Methods: 
Added protocol template language for 
contraception methods that are permitted in 
Part 2. 
9. Minor typographical errors and inconsistencies 
corrected as applicable. 
Amendment 1 
20 November 
2020 
The protocol was revised to address regulatory 
comments from the FDA. Changes incorporated 
include the following: 
1. Sections 1.1 and 4.1.1. Initiation of the multiple 
dose, 15 mg SC dose level (Cohort 10) will occur 
after the SAD 100 mg IV dose cohort (Cohort 6) 
completes. Previously MAD Cohort 10 was 
planned to start after completion of the SAD 30 
mg IV cohort (Cohort 5). 
2. Multiple sections (1.1, 1.2, 3.1, 4 and 8). Cohort 8 
(1000 mg IV), the highest planned dose, will be 
conducted in healthy participants. Previously 
Cohort 8 was intended initially in AD 
participants. 
This change also affected number of participants 
enrolled in Part 1 SAD from 49 to 57 healthy 
participants, in Part 2 from 57 to 48. AD 
participants, and overall number of participants 
from 146 to 145 participants. 
3. Section 7.1 and Appendix 3. Added criteria for 
permanent discontinuation of study intervention 
for any Grade 2 or higher adverse events in the 
blood/bone marrow or cardiac categories; or any 
Grade 3 or higher adverse event, as defined by 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 4 
 
 
 
CTCAE criteria. 
4. Section 6.6.1. Revised cohort stopping criteria to 
stop enrollment of a cohort if 2/3 of participants 
in a cohort develop a defined stopping AE. 
Previously criteria was 2 patients on active study 
drug experienced AEs possibly related to study 
intervention. 
5. Minor typographical errors have been corrected 
throughout the document. 
Original 
Protocol 
30 September 
2020 
N/A 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 5 
 
 
TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 11 
LIST OF FIGURES .................................................................................................................. 11 
1. PROTOCOL SUMMARY ................................................................................................... 12 
1.1. Schema..................................................................................................................... 19 
1.2. Schedule of Activities .............................................................................................. 20 
2. INTRODUCTION ................................................................................................................ 30 
2.1. Study Rationale ........................................................................................................ 30 
2.2. Background .............................................................................................................. 30 
2.2.1. Nonclinical Overview ................................................................................. 30 
2.2.1.1. Nonclinical Pharmacology ......................................................... 31 
2.2.1.2. Nonclinical Safety ..................................................................... 31 
2.2.1.3. Nonclinical PK .......................................................................... 32 
2.2.1.4. Immunogenicity Risk Assessment ............................................. 32 
2.2.2. Clinical Overview ....................................................................................... 33 
2.3. Benefit/Risk Assessment ......................................................................................... 33 
2.3.1. Risk Assessment ......................................................................................... 34 
2.3.2. Benefit Assessment ..................................................................................... 36 
2.3.3. Overall Benefit/Risk Conclusion ................................................................ 36 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................................ 36 
3.1. Objectives and Endpoints: Part 1 (Healthy Adult Participants) ............................... 36 
3.2. Objectives, Endpoints and Estimands: Part 2 (Atopic Dermatitis Participants) ...... 37 
4. STUDY DESIGN ................................................................................................................. 40 
4.1. Overall Design ......................................................................................................... 40 
4.1.1. Part 1: Single and Multiple Ascending Dose in Healthy Participants ......... 40 
4.1.2. Part 2: Participants with Atopic Dermatitis................................................. 43 
4.2. Scientific Rationale for Study Design ..................................................................... 43 
4.2.1. Study Design Rationale for Part 1 ............................................................... 43 
4.2.2. Study Design Rationale for Part 2............................................................... 45 
4.3. Justification for Dose ............................................................................................... 46 
4.3.1. Prediction of Human PK and Efficacious dose ........................................... 46 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 6 
 
 
4.3.2. Dose Rationale for Part 1 ............................................................................ 47 
4.3.3. Dose Rationale for Part 2 ............................................................................ 48 
4.4. End of Study Definition ........................................................................................... 49 
5. STUDY POPULATION ...................................................................................................... 49 
5.1. Inclusion Criteria ..................................................................................................... 49 
5.2. Exclusion Criteria .................................................................................................... 51 
5.3. Lifestyle Considerations .......................................................................................... 55 
5.3.1. Meals and Dietary Restrictions ................................................................... 55 
5.3.2. Alcohol, Caffeine and Tobacco ................................................................... 55 
5.3.3. Activity ....................................................................................................... 56 
5.3.4. Contraception .............................................................................................. 56 
5.4. Screen Failures ......................................................................................................... 56 
6. STUDY INTERVENTION .................................................................................................. 57 
6.1. Study Intervention(s) Administered ......................................................................... 57 
6.1.1. Administration ............................................................................................. 57 
6.2. Preparation/Handling/Storage/Accountability .......................................................... 57 
6.2.1. Preparation and Dispensing ......................................................................... 59 
6.3. Measures to Minimize Bias: Randomization and Blinding ..................................... 59 
6.3.1. Allocation to Study Intervention ................................................................. 59 
6.3.2. Breaking the Blind ...................................................................................... 60 
6.4. Study Intervention Compliance ............................................................................... 60 
6.5. Concomitant Therapy .............................................................................................. 60 
6.5.1. Concomitant Treatments in Part 1 .............................................................. 61 
6.5.2. Concomitant Treatments in Part 2 .............................................................. 61 
6.5.2.1. Permitted During Study ............................................................. 61 
6.5.2.2. Prohibited Treatments and Medications During the Study ....... 62 
6.5.3. Rescue Medicine ......................................................................................... 64 
6.6. Dose Modification ................................................................................................... 65 
6.6.1. Dose Escalation and Stopping Rules (Part 1).............................................. 65 
6.7. Intervention After the End of the Study .................................................................. 66 
7. DISCONTINUATION OF STUDY INTERVENTION AND OF STUDY 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................................. 66 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 7 
 
 
7.1. Discontinuation of Study Intervention .................................................................... 66 
7.1.1. Temporary Discontinuation ........................................................................ 67 
7.2. Participant Discontinuation/Withdrawal From the Study ...................................... 67 
7.2.1. Withdrawal of Consent .............................................................................. 68 
7.3. Lost to Follow-up ................................................................................................... 68 
8. STUDY ASSESSMENTS AND PROCEDURES .............................................................. 69 
8.1. Assessments of Clinical Effect (Participants with Atopic Dermatitis [Part 2]) ...... 70 
8.1.1. Fitzpatrick Skin Type Assessment ............................................................. 70 
8.1.2. Eczema Area and Severity Index (EASI) .................................................. 70 
CCI 
 
8.1.4. Columbia Suicide Severity Rating Scale (C-SSRS) .................................. 70 
8.1.5. Patient Reported Outcome Measures ......................................................... 70 
8.1.5.1. POEM ....................................................................................... 70 
8.1.5.2. Pruritus Numerical Rating Scale (Pruritus NRS) ..................... 71 
8.1.5.3. Patient Global Assessment (PtGA) .......................................... 71 
8.1.5.4. Dermatology Life Quality Index (DLQI) ................................. 71 
8.1.5.5. Hospital and Anxiety Depression Scale (HADS) ..................... 72 
8.1.5.6. Asthma Control Questionnaire, 5 Item Version (ACQ-5) 
(Asthmatic Participants only) ........................................................... 72 
8.1.6. Rater Qualifications ................................................................................... 72 
8.2. Safety Assessments ................................................................................................. 72 
8.2.1. Physical Examinations ............................................................................... 72 
8.2.2. Vital Signs .................................................................................................. 73 
8.2.3. Electrocardiograms ..................................................................................... 73 
8.2.3.1. Continuous Cardiac Monitoring by Telemetry ......................... 74 
8.2.4. Clinical Safety Laboratory Assessments .................................................... 75 
8.2.5. Pregnancy Testing ...................................................................................... 75 
8.2.6. Infusion and Injection Site Reaction Assessment ...................................... 75 
8.3. Adverse Events and Serious Adverse Events ......................................................... 76 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ...... 76 
8.3.1.1. Reporting SAEs to Pfizer Safety .............................................. 77 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF .................. 77 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 8 
 
 
8.3.2. Method of Detecting AEs and SAEs ........................................................... 77 
8.3.3. Follow-up of AEs and SAEs ....................................................................... 77 
8.3.4. Regulatory Reporting Requirements for SAEs ........................................... 78 
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ........................................................................................................... 78 
8.3.5.1. Exposure During Pregnancy ...................................................... 78 
8.3.5.2. Exposure During Breastfeeding ................................................. 80 
8.3.5.3. Occupational Exposure .............................................................. 80 
8.3.6. Cardiovascular and Death Events ................................................................ 80 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................. 80 
8.3.8. Adverse Events of Special Interest ............................................................. 81 
8.3.8.1. Lack of Efficacy ........................................................................ 81 
8.3.9. Medical Device Deficiencies ...................................................................... 81 
8.3.10. Medication Errors ...................................................................................... 81 
8.4. Treatment of Overdose ............................................................................................ 82 
8.5. Pharmacokinetics ..................................................................................................... 82 
8.6. Pharmacodynamics .................................................................................................. 83 
8.6.1. Skin Biopsies .............................................................................................. 83 
8.7. Genetics ................................................................................................................... 84 
8.7.1. Specified Genetics ....................................................................................... 84 
8.7.2. Banked Biospecimens for Genetics ............................................................. 84 
8.8. Biomarkers ............................................................................................................... 84 
8.8.1. Specified Gene Expression (RNA) Research .............................................. 84 
8.8.1.1. Skin Biopsies for RNA Analysis ............................................... 84 
8.8.2. Specified Cellular Research ........................................................................ 85 
8.8.2.1. Skin Biopsies for Histopathology and Immuno- 
histopathology .................................................................................... 85 
8.8.2.2. Lymphocyte Subsets .................................................................. 85 
8.8.3. Specified Protein Research.......................................................................... 85 
8.8.3.1. Total IgE .................................................................................... 85 
8.8.3.2. TARC/CCL17 ............................................................................ 85 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 9 
 
 
8.8.3.3. Interleukin 31 and Interleukin 17A ........................................... 85 
8.8.3.4. Cytokines .................................................................................. 86 
8.8.3.5. Anterior Pituitary Hormones and Hormones under 
Anterior Pituitary Regulatory Control .............................................. 86 
8.8.4. Specified Metabolomic Research ............................................................... 86 
8.8.5. Banked Biospecimens for Biomarkers ....................................................... 86 
8.9. Immunogenicity Assessments ................................................................................ 87 
8.10. Health Economics ................................................................................................. 87 
9. STATISTICAL CONSIDERATIONS ................................................................................ 87 
9.1. Estimands and Statistical Hypotheses..................................................................... 87 
9.2. Sample Size Determination .................................................................................... 88 
9.2.1. Healthy Participant Single Ascending and Multiple Dose (Part 1) ............ 88 
9.2.2. Atopic Dermatitis Cohorts (Part 2) ............................................................ 89 
9.3. Analysis Sets ........................................................................................................... 89 
9.4. Statistical Analyses ................................................................................................. 89 
9.4.1. Efficacy Analyses (Part 2 Only) ................................................................ 90 
9.4.2. Safety Analyses .......................................................................................... 91 
9.4.2.1. Electrocardiogram Analyses ..................................................... 91 
9.4.3. Pharmacokinetics Analyses ....................................................................... 92 
9.4.3.1. Analysis Population .................................................................. 92 
9.4.3.2. Derivation of Pharmacokinetic Parameters .............................. 92 
9.4.3.3. Statistical Methods for PK Data ............................................... 94 
9.4.4. Pharmacodynamic Analysis ....................................................................... 95 
9.4.5. Other Analyses ........................................................................................... 95 
9.5. Interim Analysis...................................................................................................... 95 
9.6. Data Monitoring Committee or Other Independent Oversight Committee ............ 95 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.......................................................................................................... 96 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............... 96 
10.1.1. Regulatory and Ethical Considerations .................................................... 96 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................ 96 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 10 
 
 
10.1.2. Financial Disclosure ................................................................................. 97 
10.1.3. Informed Consent Process ....................................................................... 97 
10.1.4. Data Protection ......................................................................................... 98 
10.1.5. Dissemination of Clinical Study Data ...................................................... 98 
10.1.6. Data Quality Assurance .......................................................................... 100 
10.1.7. Source Documents ................................................................................. 101 
10.1.8. Study and Site Start and Closure ............................................................ 101 
10.1.9. Publication Policy .................................................................................. 102 
10.1.10. Sponsor’s Qualified Medical Personnel ............................................... 103 
10.2. Appendix 2: Clinical Laboratory Tests .............................................................. 104 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting .................................................................... 105 
10.3.1. Definition of AE ..................................................................................... 105 
10.3.2. Definition of SAE .................................................................................. 106 
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs .................... 108 
10.3.4. Reporting of SAEs ................................................................................. 111 
10.4. Appendix 4: Contraceptive Guidance ................................................................. 112 
10.4.1. Male Participant Reproductive Inclusion Criteria ................................. 112 
10.4.2. Female Participant Reproductive Inclusion Criteria .............................. 112 
10.4.3. Woman of Childbearing Potential .......................................................... 112 
10.4.4. Contraception Methods .......................................................................... 113 
10.5. Appendix 5: Genetics ......................................................................................... 115 
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up ........................... 116 
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ................................. 118 
10.8. Appendix 8: Fitzpatrick Skin Type .................................................................... 120 
10.9. Appendix 9: EASI .............................................................................................. 121 
CCI 
 
10.11. Appendix 11: Patient-Oriented Eczema Measure (POEM) .............................. 125 
10.12. Appendix 12: Pruritus NRS, Severity and Frequency ...................................... 126 
10.13. Appendix 13: Patient Global Assessment (PtGA) ............................................ 127 
10.14. Appendix 14: Hospital and Anxiety Depression Scale (HADS) ...................... 128 
10.15. Appendix 15: Columbia Suicide Severity Rating Scale (C-SSRS) .................. 129 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 11 
 
 
10.16. Appendix 16: Diagnostic Criteria for Atopic Dermatitis .................................. 132 
10.17. Appendix 17: Dermatology Life Quality Index (DLQI) ................................... 133 
10.18. Appendix 18: Clinical Criteria for Diagnosing Anaphylaxis Guidance 
(Sampson et al. 2006)18 ....................................................................................................................................... 134 
10.19. Appendix 19. Asthma Control Questionnaire12......................................................................... 135 
10.20. Appendix 20: Abbreviations .............................................................................. 137 
11. REFERENCES ................................................................................................................. 142 
 
LIST OF TABLES 
Table 1. 
Part 1. Schedule of Activities for Single Ascending Doses in 
Healthy Participants, (Cohorts 1-8) and Japanese Cohort (Cohort 
15) ............................................................................................................ 20 
Table 2. 
Part 1. Schedule of Activities for Multiple Ascending Doses in 
Healthy Participants (Cohorts 10-14) ....................................................... 23 
Table 3. 
Part 2. Schedule of Activities in AD Participants – Cohort 9 .................. 27 
Table 4. 
Projected Exposures, Maximum CD1a Receptor Occupancy and 
Safety Margins Following Single IV Doses of PF-07242813a ......................... 47 
Table 5. 
Projected Exposures, Maximum CD1a RO and Safety Margins 
After the 3rd Dose of Multiple SC or IV Doses of PF-07242813a .................. 48 
Table 6. 
Serum PK Parameters for Part 1 .............................................................. 93 
Table 7. 
Protocol-Required Safety Laboratory Assessments ............................... 104 
Table 8. 
Clinical Sign Severity Scoring Criteria for the Eczema Area and 
Severity Index (EASI) ............................................................................ 121 
Table 9. 
Handprint Determination of Body Region Surface Area (BSA) ............ 122 
Table 10. 
Eczema Area and Severity Index (EASI) Area Score Criteria ............... 122 
Table 11. 
Eczema Area and Severity Index (EASI) Body Region Weighting ....... 123 
 
 
LIST OF FIGURES 
Figure 1. 
C4461001 Study Design with Planned Doses .......................................... 19 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 12 
 
 
1. PROTOCOL SUMMARY 
Synopsis 
 
Short Title: A Phase 1 Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy 
Participants and Participants with Atopic Dermatitis. 
 
Rationale 
 
This is the first time PF-07242813 will be given to humans. The purpose of the study is to 
evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of 
PF-07242813 in healthy participants and participants with moderate to severe atopic 
dermatitis. CCI 
 
 
 
Objectives, Estimands, and Endpoints 
 
Objectives and Endpoints Part 1 (Healthy Adult Participants) 
 
PF-07242813 serum exposure as data permit: AUClast, 
AUCinf, Cmax, Tmax and t1/2 after single doses; AUCτ, 
Cmax, and Tmax after each repeated dose; and t1/2 after the 
last repeated dose. 
To characterize the serum exposure of 
PF-07242813, following single and multiple 
doses in healthy adults. 
Secondary: 
Secondary: 
Incidence of treatment-emergent adverse events (AEs 
and SAEs); vital signs, safety laboratory tests, cardiac 
telemetry (SAD only), and ECG. 
To evaluate the safety and tolerability of 
PF-07242813, following single and multiple 
doses in healthy adults. 
Primary: 
Primary: 
Endpoints 
Objectives 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 13 
 
 
 
 
 
 
Objectives, Endpoints and Estimands Part 2 (Atopic Dermatitis Participants) 
 
Objectives 
Endpoints 
Estimands 
Primary: 
Primary: 
Primary: 
To evaluate the safety and 
tolerability of PF-07242813 
versus placebo, in 
participants with moderate 
to severe AD. 
Incidence of treatment-emergent 
adverse events (AEs and SAEs); vital 
signs, safety laboratory tests, and 
ECG. 
There is no defined estimand for these 
endpoints; they will be analyzed using 
CaPS as applicable. 
Secondary: 
Secondary: 
Secondary: 
To compare the efficacy of 
PF-07242813 versus 
placebo on percent change 
from baseline in Eczema 
Area and Severity Index 
(EASI) in participants with 
moderate to severe 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 
study intervention on a continuous 
endpoint; without prohibited 
medications during treatment. 
Study Intervention: PF-07242813 or 
placebo. 
Population: Participants with moderate 
to severe AD as defined by the 
inclusion and exclusion criteria. 
Variable: Percent change from 
baseline in EASI total score at 
Week 6. 
Intercurrent Events: 
a. 
Prohibited medications – all 
scores in participants who receive 
prohibited medication post 
randomization to Week 6 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 study 
intervention. 
b. Inadequate compliance – 
participants data will be used as 
recorded. 
Events a and b are stated with 
Endpoints 
Objectives 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 14 
 
 
 
Objectives 
Endpoints 
Estimands 
precedence in descending order. 
Population level summary: 
The percent change from baseline 
mean difference between 
PF-07242813 and placebo in EASI 
score. 
CCI 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 15 
 
 
Objectives 
Endpoints 
Estimands 
 
 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 16 
 
 
 
 
 
Overall Design 
This is a first-in-human (FIH) study of PF-07242813 that will be conducted in 2 parts: Part 1 
will be conducted in healthy adult participants and Part 2 will be conducted in adult 
participants with moderate to severe AD (see Figure 1). 
Part 1 is within-cohort randomized, participant- and investigator-blind, sponsor-open, 
placebo-controlled investigation of the safety, tolerability, PK, and immunogenicity 
following single and multiple ascending doses of PF-07242813 in healthy participants. Part 1 
will also include a cohort of Japanese healthy adult participants (Cohort 15) to provide 
safety, tolerability, and PK data in Japanese population to enable the inclusion of Japanese 
participants in future clinical trials. 
Part 2 is a randomized, participant- and investigator-blind, sponsor-open, placebo-controlled 
investigation of the safety, tolerability, PK, and pharmacodynamics (including clinical 
effects) of PF-07242813 in adult participants with moderate to severe atopic dermatitis (AD). 
In Part 2, Cohort 9 will randomize (2:1, PF-07242813:placebo) 24 participants at the MTD 
defined in Part 1 (or maximum dose studied in Part 1 if MTD is not achieved) for the 
assessment of the safety, tolerability, PK, and clinical effects of PF-07242813 in AD and 
CCI 
 evaluations of pharmacodynamic activity. The number of participants 
enrolled in Cohort 9 will provide a sample size sufficient for statistical evaluation of the 
primary efficacy endpoint (placebo-corrected percent change from baseline in continuous 
EASI). 
Number of Participants 
Up to approximately 145 participants will be randomly assigned to study intervention, either 
PF-07242813 or placebo. 
In Part 1, up to approximately 57 healthy participants, including a cohort of 5 healthy 
Japanese participants, will be randomly assigned to receive a single dose of study 
intervention (SAD). Up to approximately 40 healthy participants, including an optional 
cohort, will be randomly assigned to receive multiple doses of study intervention (MAD). 
CCI 
 
Estimands 
Endpoints 
Objectives 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 17 
 
 
In Part 2, 24 participants with moderate to severe AD will be randomly assigned to a single 
dose of study intervention in Cohort 9. An optional cohort (Cohort 16) of up to 
24 participants with AD may be enrolled to evaluate further IV or SC dosing, based on 
cumulative safety and PK data from Part 1 and Cohort 9. 
 
Intervention Groups and Duration 
 
Part 1 SAD: Within 28 days of successful completion of the screening process, eligible 
participants for the single ascending dose period will be enrolled and randomized to receive a 
single IV infusion of PF-07242813 or placebo. 
 
As illustrated in Figure 1, healthy participants in the SAD phase of the study will be 
randomized sequentially into 8 single dose cohorts (Cohorts 1-8). Participants will be 
admitted into the clinic approximately 1 day prior to dosing and be required to stay confined 
in the clinic through completion of Day 5 evaluations. Participants in the single dose cohorts 
will return for outpatient visits up to Day 71 (or at least 4 half-lives of PF-07242813 based on 
observed data). For Cohort 1, the outpatient visit is up to Day 29 (±3 days). For Cohorts 2 
and 3, the last follow-up visit will be determined based on emerging safety and PK data from 
previous cohort(s). As such, the last follow-up visit (and discharge from the study) may occur 
earlier than Day 71 (±3 days), but will be at least through Day 29 (±3 days). 
 
During the SAD period, escalation to subsequent dose levels will only occur if the sponsor’s 
review of the available safety and PK data for the previous cohorts suggest that the next dose 
is likely to have acceptable safety and tolerability. There will be a minimum of 10 days 
between cohorts for dose escalation. Dosing in SAD (up to the maximum dose of 1000 mg 
IV) may be adjusted depending upon the actual exposure of PF-07242813 observed in 
humans at lower doses. If, based on the observed data, the subsequent dose projected group 
mean Cmax is >1020 µg/mL or AUC168H >106000 µg.h/mL, the exposure limits pre-specified, 
that dose will not be explored. 
 
In addition, a cohort of healthy Japanese adults (Cohort 15, n=5) will be enrolled to receive a 
single IV dose of PF-07242813 or placebo (active:placebo,=4:1). This cohort will be initiated 
after single dose escalation in healthy participants is complete and will enroll in parallel to 
Part 2. 
 
Part 1 MAD: Four (4) escalating multiple SC dose cohorts and 1 optional multiple IV dose 
cohort in healthy participants are planned. Initiation of the multiple dose at 15 mg SC 
(Cohort 10) dose is planned to begin following the Sponsor’s review of available safety data 
through study Day 8 and PK data through study Day 3 from the 100 mg single IV dose 
cohort (Cohort 6), as well as the accumulated safety data from the previous IV single dose 
cohorts. The starting dose for the initial multiple dose cohort may be adjusted, based on 
emerging safety and PK data from single dose cohorts. Doses and/or dosing regimens 
planned may be modified based on emerging data from earlier single and multiple dose 
cohorts. If the exposures in the subsequent dose is projected to exceed the exposure limits 
pre-specified, after repeat doses, that dose will not be explored. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 18 
 
 
Healthy participants who are enrolled into the multiple dose cohorts (Cohorts 10-14) will be 
randomized 3:1 to receive PF-07242813 or placebo every 2 weeks (Q2W) for a total of 
3 doses. Participants will be confined to the clinical research unit starting on the day prior to 
dosing and through at least 96 hours after the first dose of study intervention administration 
and 48 hours after the second and third doses. Participants will return for outpatient visits at 
least through Day 99 visit (or at least 4 half-lives of PF-07242813 based on observed data). 
Part 2 Atopic Dermatitis: At least 1 cohort of adult participants with moderate to severe 
AD (Cohort 9, n=24) will be randomized 2:1 to receive a single dose of either PF-07242813 
or placebo. 
Cohort 9 will be initiated following completion of all single dose cohorts evaluated in Part 1 
and review of cumulative safety and PK data from Part 1. Participants in Cohort 9 will 
receive study intervention on Day 1 at the MTD defined in Part 1 (or the highest dose studied 
in Part 1 if MTD is not achieved). All study visits will be done on an outpatient basis through 
the last scheduled visit on Day 113 (Week 16). 
An optional cohort of up to 24 moderate to severe AD participants (Cohort 16) may be 
enrolled as needed to evaluate further IV or SC dosing of PF-07242813, based on cumulative 
safety and PK data from Part 1 and Cohort 9 in Part 2. 
Participants who prematurely discontinue from the study for reasons other than safety may be 
replaced, at the discretion of the investigator and Sponsor. 
Data Monitoring Committee or Other Independent Oversight Committee: This Phase 1 
study will not have a DMC or other independent oversight committee. 
Statistical Methods 
Safety data will be summarized in accordance with CDISC/CaPS. All participants who 
receive study intervention (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. 
In Part 2, the secondary objective will be to evaluate the effect of PF-07242813 on clinical 
indices of AD activity with the secondary endpoint being percent changes in EASI score 
from baseline at Week 6. The primary estimand will be the population average treatment 
effect on percent change from baseline in EASI score relative to placebo at 6 weeks in the 
absence of prohibited medication. All observations after the initiation of prohibited 
medication will be set to missing. Missing data from all causes, including post-prohibited 
medication use will be imputed in the PF-07242813 dose arms using a jump to control 
method using the distribution of the placebo group. 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined in this protocol 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
 
 
1.1. Schema 
Figure 1. C4461001 Study Design with Planned Doses 
 
 
Doses shown for each cohort are planned doses and may be modified based on emerging data from previous cohorts. 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 19 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 20 
 
 
 
1.2. 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. 
 
Table 1. 
Part 1. Schedule of Activities for Single Ascending Doses in Healthy Participants, (Cohorts 1-8) and Japanese 
Cohort (Cohort 15) 
 
Visit Identifier 
Screening 
Clinical Confinement 
Outpatient Visits 
EOSi 
Early 
Termination 
Day relative to dose (Day 1) Day-28 to 
Day-2 
Day 
-1 
Day 1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
8 
±3 
Day 
15 
±3 
Day 
29 
±3 
Day 
43 
±3 
Day 
57 
±3 
Day 
71 
±3 
Hours After Dose (for 
clinical confinement portion) 
-2 hrs to 
-5 min 
0 
End of 
infusiona 
2a 
6a 
12a 24a 48a 
72a 96a 
Informed consent 
X 
Demography, Medical history 
X 
Update to medical history 
X 
Physical examinationb 
X 
X 
X 
Height 
X 
Body Weight 
X 
X 
History of Drug, Alcohol, and 
Tobacco use 
X 
Inclusion/Exclusion Review 
X 
X 
Admission to Clinical 
Research Unit 
X 
Randomizationl 
X 
Laboratory (hematology, 
blood chemistry, urinalysis) 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Drug Test 
X 
X 
Serum FSHc 
X 
Urine Pregnancy Testj 
X 
X 
X 
X 
X 
X 
HIV, HBsAg, HBcAb, 
HCVAb 
X 
QuantiFERON TB Gold 
X 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 21 
 
 
 
Visit Identifier 
Screening 
Clinical Confinement 
Outpatient Visits 
EOSi 
Early 
Termination 
Day relative to dose (Day 1) Day-28 to Day 
Day 1 
Day Day Day Day 
Day 
Day 
Day Day 
Day 
Day 
 
 
Hours After Dose (for 
clinical confinement portion) 
Sample forCCI 
cytokine analyses (TNFα, IL-6 
total, and IFNγ)d 
Continuous Cardiac 
Monitoring by Telemetrye 
Day-2 
-1 
 
-2 hrs to 
-5 min 
 
 
0 
 End of 
infusiona 
 
 
2a 
6a  12a 
2 
 
24a 
3 
 
48a 
4 
 
72a 
5 
8 
±3 
96a 
15 
29 
43 
57 
71 
±3 
±3 
±3 
±3 
±3 
12-Lead ECGf 
Vital Signsg 
Prior/Concomitant Medication 
Study Intervention 
Administration 
Infusion/Injection Site 
Reaction Assessment 
PK blood sampling 
CCI 
Banked Biospecimens for 
Genetics Prep D1h 
Banked Biospecimens for 
Biomarkers Prep B2.5 
Sample(s) CCI 
analyses of hormone levels: 
HGH, IGF-1, TSH, T4 and 
Cortisolk 
Adverse event monitoring 
Discharge from Clinic 
X 
X 
X 
 
 
 
 
 
 
 
 
 
CCI 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
→ 
→ 
→ 
 
 
 
 
 
 
 
 
 
 
 
 
 
→ 
→  →  → 
→ 
→ 
→ 
→ 
X 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
→ 
→ 
→ 
→ 
X 
X 
a. 
Procedures should be completed within ±10% of the collection time (ie, 2 hours ±12 minutes; 6 hours ±36 minutes, etc). 
b. 
A full PE may be done at screening or deferred to Day -1 at the discretion of the principal investigator. A limited PE will be performed at discharge; a full PE may be 
performed instead, at the discretion of the Investigator. At any time during the study, a limited PE may be performed at the discretion of the investigator if there is a new or 
ongoing AE. 
c. 
FSH test is performed only in WONCBP at screening to confirm postmenopausal status in females who have been amenorrhoeic for at least 12 consecutive months. 
d. 
Biospecimens for exploratory cytokine analyses will be collected pre-dose (-2 hrs to -5 min), 30 minutes (±5 min) after the end of infusion, 2, 12, 24 and 48 hours after 
IV infusion starts. Biospecimens will be analyzed ad hoc based on clinical signs of cytokine release syndrome. 
e. 
To establish a baseline, telemetry should be recorded for at least 2 hours before dosing. This may be done immediately prior to dosing or at some 2 hour continuous interval in 
the 24 hours prior to dosing, as long as the recording is performed when the participant is awake. Continuous cardiac monitoring will be conducted -15 minutes pre-dose 
through the 8 hour post dose period. 
X
X 
→ 
→ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 22 
 
 
 
f. 
ECGs will be collected in triplicate approximately 2-4 minutes apart at pre-dose, and during clinical confinement at the times specified in the Schedule of Activities (Day 1 
prior to dose to morning of Day 5, ie 96 hours post-dose). Single ECGs will be collected at all other designated visits. 
g. 
Vital signs include supine blood pressure, pulse rate, respiratory rate, and temperature. 
h. 
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a participant visit. 
i. 
For Cohort 1, the follow-up visit is up to Day 29 (±3 days). For Cohorts 2 and 3, the final follow-up visit will be determined based on safety and PK data emerging from 
previous cohort(s), which may be earlier than Day 71 (±3 days) but will be at least through Day 29 (±3 days). 
j. 
Pregnancy test is performed only in WOCBP. 
k. 
Hormone samples will be collected in the morning. Beginning at baseline visit (Day -1 or predose Day 1), samples should be collected at approximately the same time in the 
morning. 
l. 
Randomization may be performed Day -1, or prior to first dose on Day 1. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 23 
 
 
 
Table 2. 
Part 1. Schedule of Activities for Multiple Ascending Doses in Healthy Participants (Cohorts 10-14) 
Screening to Day 8 Visits (1st Dose) 
Visit Identifier 
Screening 
Clinical Confinement 
Out-patient 
Visit 
Early 
Termination 
Study Day 
Day-28 to 
Day-2 
Day 
-1 
Day 1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 8 
±1 day 
Hours After Dose (for clinical 
confinement portion) 
-2 hrs to 
-5 min 
0 
End of 
infusionb,e 
2b 
6b 
12b 
24b 
48b 
72b 
96b 
Informed consent 
X 
Demography, Medical history 
X 
Update to medical history 
X 
Physical examinationc 
X 
X 
Height 
X 
Body Weight 
X 
Xa 
History of Drug, Alcohol, and 
Tobacco use 
X 
Inclusion/Exclusion Review 
X 
Xa 
Admission to Clinical Research Unit 
X 
Randomization 
Xa 
Discharge from Clinic 
X 
X 
Laboratory (hematology, blood 
chemistry, urinalysis) 
X 
Xa 
X 
X 
X 
X 
Urine Drug Test 
X 
X 
Serum FSHd 
X 
Urine pregnancy testi 
X 
X 
X 
HIV, HBsAg, HBcAb, HCVAb 
X 
QuantiFERON – Tuberculosis Gold 
X 
12-Lead ECGf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Intervention Administration 
X 
Infusion/Injection Site Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
Banked Biospecimens for Genetics 
Prep D1h 
X 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 24 
 
 
 
Visit Identifier 
Screening 
Clinical Confinement 
Out-patient 
Visit 
Early 
Termination 
Study Day 
Day-28 to 
Day-2 
Day 
-1 
Day 1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 8 
±1 day 
Hours After Dose (for clinical 
confinement portion) 
-2 hrs to 
-5 min 
0 
End of 
infusionb,e 
2b 
6b 
12b 
24b 
48b 
72b 
96b 
Sample(s) CCI 
 of 
hormone levels: HGH, IGF-1, TSH, 
T4 and Cortisolj 
CCI 
 
 
 
Banked Biospecimens for Biomarkers 
Prep B2.5 
X 
X 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a. 
Study procedures may be performed Day-1, or prior to first dose on Day 1. 
b. 
Procedures should be completed within ±10% of the collection time (ie, 2 hours ±12 minutes; 6 hours ±36 minutes, etc). 
c. 
A full PE may be done at screening or may be deferred to Day -1 at the discretion of the principal investigator. A limited PE may be performed at discharge at the discretion 
of the investigator. A limited PE may also be performed at the discretion of the investigator at a follow-up visit if there is a new or ongoing AE. 
d. 
FSH test is performed only in WONCBP at screening to confirm postmenopausal status in females who have been amenorrhoeic for at least 12 consecutive months. 
e. 
Infusion pertains only to the IV cohort and does not pertain to the SC Cohorts. 
f. 
ECGs will be collected in triplicate approximately 2-4 minutes apart at pre-dose, and during clinical confinement at the times specified above. Single ECGs will be collected 
at all other designated visits. 
g. 
Vital signs include supine blood pressure, pulse rate, respiratory rate, and temperature. 
h. 
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a participant visit. 
i. 
Pregnancy test is performed only in WOCBP. 
j. 
Hormone samples will be collected in the morning. Beginning at baseline visit (Day -1 or predose Day 1), samples should be collected at approximately the same time in the 
morning. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 25 
 
 
 
Day 14 Through Day 22 Visits (2nd Dose) 
 
Visit Identifier 
Clinical Confinement 
Out-patient 
Visit 
Early Termination 
Study Day 
Day 
14 
Day 15 
Day 
16 
Day 
17 
Day 19 
Day 22 
±1 day 
Hours After Dose (for clinical 
confinement portion) 
-2 hrs to 
-5 min 
0 
End of 
infusiona,b 
2a 
6a 12a
24a 
48a 
96a 
Admission to Clinical Research Unit 
X 
Physical examinationc 
X 
Laboratory (hematology, blood chemistry, 
urinalysis) 
X 
X 
X 
X 
Urine Drug Test 
X 
Urine Pregnancy Testf 
X 
X 
12Lead -ECGd 
X 
X 
X 
X 
X 
X 
X 
Vital Signse 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Intervention Administration 
X 
Infusion/Injection Site Reaction 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
Sample(s) forCCI 
 of 
hormone levels: HGH, IGF-1, TSH, T4 and 
Cortisolg 
CCI 
Banked Biospecimens for Biomarkers Prep 
B2.5 
X 
X 
Adverse event monitoring 
→ 
→ 
→ 
→ 
→ → → 
→ 
→ 
→ 
→ 
X 
Discharge from Clinic 
X 
a. 
Procedures should be completed within ±10% of the collection time (ie, 2 hours ±12 minutes; 6 hours ±36 minutes, etc). 
b. 
Infusion pertains only to the IV cohorts and does not pertain to the SC Cohorts. 
c. 
Physical examination prior to the second dose will be at the discretion of the investigator, based on any review of potential adverse events or other clinical signs/symptoms. 
d. 
ECGs will be collected in triplicate approximately 2-4 minutes apart at pre-dose, and during clinical confinement at the times specified in the Schedule of Activities 
(Day 15 prior to dose and up to 48 hours post-dose). Single ECGs will be collected at all other designated visits. 
e. 
Vital signs include supine blood pressure, respiratory, pulse rate, and temperature. 
f. 
Pregnancy test is performed only in WOCBP. 
g. 
Hormone samples will be collected in the morning, at the same time of day. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 26 
 
 
 
Day 28 Through Day 99 Visit (3rd Dose) 
 
Visit Identifier 
Clinical Confinement 
Out-patient Visits 
EOS 
Early 
Termination 
Study Day 
Day 
28 
Day 29 
Day 
30 
Day 
31 
Day 
33 
Day 
36 
±1 
Day 
43 
±3 
Day 
57 
±3 
Day 
71 
±3 
Day 
85 
±3 
Day 
99 
±3 
Hours After Dose (for clinical confinement 
portion) 
-2 hrs to 
-5 min 
0 
End of 
infusiona,b 
2a 
6a 
12a 
24a 
48a 96a 
Admission to Clinical Research Unit 
X 
Physical Examinationc 
X 
X 
Laboratory (hematology, blood chemistry, 
urinalysis) 
X 
X 
X 
X 
X 
X 
Urine Drug Test 
X 
Urine Pregnancy Testf 
X 
X 
X 
X 
12-Lead ECGd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signse 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
Study Intervention Administration 
X 
Infusion/Injection Site Reaction 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
 
Sample(s) forCCI 
 of 
hormone levels: HGH, IGF-1, TSH, T4 and 
Cortisolg 
CCI 
Banked Biospecimens for Biomarkers Prep 
B2.5 
X 
X 
Adverse event monitoring 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
Discharge from Clinic 
X 
a. 
Procedures should be completed within ±10% of the collection time (ie, 2 hours ±12 minutes; 6 hours ±36 minutes, etc). 
b. 
Infusion pertains only to the IV cohort and does not pertain to the SC Cohorts. 
c. 
Physical examination prior to the third dose will be at the discretion of the investigator, based on any review of potential adverse events or other clinical signs/symptoms. 
d. 
ECGs will be collected in triplicate approximately 2-4 minutes apart pre-dose, and during clinical confinement at the times specified in the Schedule of Activities (Day 29 
prior to dose and up to 48 hours post-dose). Single ECGs will be collected at all other designated visits. 
e. 
Vital signs include supine blood pressure, respiratory rate, pulse rate, and temperature. 
f. 
Pregnancy test is performed only in WOCBP. 
g. 
Hormone samples will be collected at the same time of day, in the morning. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 27 
 
 
Safety labs (hematology, blood 
chemistry, urinalysis) 
Urine Drug Test 
Pregnancy testd 
PK blood samples 
CCI 
X 
Xb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xa 
X 
Xb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical Procedures 
Physical Examinationc 
X 
X 
X 
 
Table 3. 
Part 2. Schedule of Activities in AD Participants – Cohort 9 
 
Visit Identifier 
Screening 
Week 1 
Week 2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 12 
EOS 
ET 
Week 16 
Day relative to dose (Day 1) 
Day-28 to 
Day 1 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day-2 
8 
15 
29 
43 
57 
85 
113 
Visit Window - Days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Screening Assessments 
Informed consent 
X 
Demography 
X 
Medical History (including AD) 
X 
Height 
X 
Body Weight 
Drug, Alcohol and Tobacco 
History 
FSHd 
HIV, HBsAg, HBcAb, HCVAb 
QuantiFERON TB Gold 
Inclusion/Exclusion 
Randomization 
Laboratory Assessments 
X 
X 
X 
X 
X 
X 
Xa 
Xa 
X 
Xa 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 28 
 
 
 
Visit Identifier 
Screening 
Week 1 
Week 2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 12 
EOS 
Week 16 
ET 
Day relative to dose (Day 1) 
Day-28 to 
Day-2 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
85 
Day 
113 
Visit Window - Days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
12 Lead -ECGf 
X 
Xb,f 
X 
X 
X 
X 
X 
X 
X 
X 
Spirometry (FEV1, FCV)k 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Biomarker 
Banked Biospecimens for 
Genetics Prep D1h 
Xa 
Banked Biospecimen -Prep 
PBMC2 
Xa 
X 
X 
X 
X 
X 
Banked Biospecimen -Prep R1 
Xa 
X 
X 
X 
X 
X 
Banked Biospecimens for 
Biomarkers Prep B2.5 
Xa 
X 
X 
X 
X 
X 
Serum IgE 
Xa 
X 
X 
X 
X 
X 
Serum TARC (CCL17) 
Xa 
X 
X 
X 
X 
X 
Plasma for Interleukin-31 
(IL-31) and Interleukin-17A 
(IL-17A) 
Xa 
X 
X 
X 
X 
X 
Whole Blood for Flow 
Cytometry 
Xa 
X 
X 
X 
X 
X 
Skin Punch 
Biopsies -nonlesional 
X 
Skin Punch Biopsies lesional 
X 
X 
X 
Physician Assessments 
Columbia Suicide Severity 
Rating Scale (C-SSRS) 
X 
Fitzpatrick Skin Type 
Assessment 
X 
Eczema Area and Severity 
Index (EASI) 
X 
Xa 
X 
X 
X 
X 
X 
X 
X 
X
CCI 
 
Patient Reported Outcomes 
Pruritus Numerical Rating Scale 
(Pruritus NRS)i 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
Dermatology Life Quality Index 
(DLQI) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
Patient Global Assessment 
(PtGA) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 29 
 
 
 
Visit Identifier 
Screening 
Week 1 
Week 2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 12 
EOS 
Week 16 
ET 
Day relative to dose (Day 1) 
Day-28 to 
Day-2 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
85 
Day 
113 
Visit Window - Days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Patient-Oriented Eczema 
Measure (POEM) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
Hospital and Anxiety 
Depression Scale (HADS) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
ACQ-5k 
Xa 
X 
X 
X 
Other Study Activities 
Contraception Checkd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Monitoring 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
Prior/Concomitant Treatment 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
a. 
Study procedures will be collected prior to first dose on Day 1. 
b. Day 1 will include the following: 1) pre-dose vital signs, ECG and PK CCI 
, 2) post-infusion ECG, vital signs, PK blood 
sample, and 3) 2 hours after the start of the infusion ECG, vital signs and blood samples for PK and cytokine release analyses. 
c. 
A full PE will be done at screening, or can be deferred to pre-dose on Day 1 at the discretion of the investigator. A limited PE will be conducted at all other 
timepoints indicated, or at the discretion of the investigator if clinically indicated. 
d. FSH test is performed only in WONCBP at screening to confirm postmenopausal status in females who have been amenorrhoeic for at least 12 consecutive 
months. Contraception checks and pregnancy tests will be conducted in WOCBP. 
e. 
Biospecimens for cytokine release labs will be collected pre-dose (-2 hrs to -5 min), 30 minutes (±5 min) after the end of infusion, and 2 hours after IV 
infusion starts. Biospecimens will be analyzed ad hoc based on clinical signs of cytokine release. 
f. 
ECGs will be collected in triplicate approximately 2-4 minutes apart pre-dose, immediately after infusion prior to PK blood collection, and at 2 hours after 
infusion start, prior to PK blood collection. Single ECGs will be collected at all other designated visits. 
g. Vital signs include supine blood pressure, pulse rate, respiratory rate, and temperature. 
h. If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit. 
i. 
Pruritis NRS to be completed by participants every day for 14 days at home after the Day 1 dosing visit. Note that Pruritis NRS has 2 scales, one for severity 
and one for frequency. See Section 8.1.5.2.1 and 8.1.5.2.2. 
j. 
Hormone samples should be collected in the morning, at the same time each day. Beginning at baseline visit (Day -1 or predose Day 1), samples should be 
collected at approximately the same time in the morning. 
k. Spirometry measures (FEV1, FCV) will be assessed for all participants at Screening. Spirometry and ACQ-5 during active study assessments of spirometry 
and ACQ-5 are required for participants with asthma. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 30 
 
 
CCI 
2. INTRODUCTION 
PF-07242813 is an anti-CD1a antibody that is being developed as a treatment for patients 
with moderate to severe atopic dermatitis. 
 
2.1. Study Rationale 
This is the first time PF-07242813 will be given to humans. The purpose of the study is to 
evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of 
PF-07242813 in healthy participants and in participants with moderate to severe atopic 
dermatitis. 
 
 
2.2. Background 
AD is a common inflammatory skin disease, especially in children with a prevalence of 
5-20% and ~11% in the total population of the US (Oyoshi et al. 2009; Williams 2005).15,20 
Current treatments for AD include emollients, and topical anti-inflammatory agents such as 
corticosteroids and calcineurin inhibitors. These agents have generally been unsatisfactory 
for the treatment of moderate to severe disease. More recently, an injectable monoclonal 
antibody directed against the IL-4 receptor α (dupilumab) that blocks the binding of IL-4 and 
IL-13 has been approved for the treatment of moderate to severe AD. While dupilumab 
represents a considerable advance in the treatment of AD, not all patients respond well or 
achieve completely clear skin. Moreover, some patients may become refractory to dupilumab 
with prolonged dosing. Additional treatments are needed that are complementary to currently 
approved drugs that increase the proportion of patients achieving complete resolution of skin 
inflammation and/or are effective in patients who do not respond or become refractory to 
dupilumab. 
 
CD1a is an MHC class I-like molecule expressed on Langerhans cells in the skin. CD1a 
presents lipid antigens found in the skin which can be recognized by antigen-specific T cells, 
leading to subsequent T cell activation (de Jong et al. 2014).7 Emerging data suggest that 
pathogenic lipids, signaling through CD1a, may be important drivers of inflammation in AD 
(Berdyshev et al. 2018; Cooper 1994; Cully 2016; Jarrett et al. 2016; Kim et al. 
2016).1,5,6,11,13 
 
PF-07242813 is a novel humanized monoclonal antibody that binds CD1a protein with high 
affinity and selectivity. PF-07242813 prevents CD1a from interacting with T cell receptors, 
leading to the inhibition of T cell activation. Therefore, PF-07242813 would be expected to 
inhibit T cell activation and downstream proinflammatory signaling. This mechanism would 
be distinct from currently available treatments that are either broadly immunosuppressive 
(eg, corticosteroids and calcineurin inhibitors) or specifically targeted to type 2 inflammation 
(eg, dupilumab). 
 
2.2.1. Nonclinical Overview 
The pharmacology and safety of PF-07242813 are supported by nonclinical studies. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 31 
 
 
2.2.1.1. Nonclinical Pharmacology 
In vitro assessments using several methods have demonstrated that PF-07242813 binds to 
both human and cynomolgus monkey CD1a with similar high affinity. SPR analysis 
demonstrated high affinity binding to recombinant forms of both human and cynomolgus 
monkey CD1a. Flow cytometry studies showed that PF-07242813 bound surface-expressed 
human and cynomolgus monkey CD1a, whether exogenously expressed by transfection into 
CHO cells or endogenously expressed on monocyte-derived dendritic cells. PF-07242813 
suppressed IL-2 secretion and upregulation of CD69 expression on Jurkat76-BK6 cells, a 
CD1a-restricted T cell line, during co-culture with human CD1a expressing cells. In vitro, 
IL-17A secretion by primary CD3+ cells, isolated from either whole blood or healthy skin, in 
response to CD1a stimulation was suppressed by PF-07242813. Likewise, PF-07242813 was 
able to suppress IL-17A secretion by primary cynomolgus monkey CD3+ cells when 
co-cultured with cells expressing cynomolgus monkey CD1a. 
 
Additionally, PF-07242813 was shown functionally to neutralize CD1a-dependent immune 
responses in vivo using human CD1a transgenic mice with an HDM-induced model of skin 
inflammation. PF-07242813, when administered in vivo in a prophylactic dosing regime, 
resulted in a statistically significant decrease of all AD measurements assessed, including 
dermatitis score, total IgE levels, HDM-specific IgE titers, presence of inflammatory or 
IL-13+ cells in the skin, and presence of an AD gene signature in the skin. 
Taken as a whole, these data demonstrate PF-07242813 neutralizes CD1a-dependent T cell 
activation and inflammation supporting its development as a novel therapeutic for the 
treatment of AD. 
 
2.2.1.2. Nonclinical Safety 
No test article-related effects or target organs were identified following once weekly 
administration of PF-07242813 to cynomolgus monkeys for 13 weeks in the GLP toxicity 
study that would predict a safety risk for participants in early clinical studies. The NOAEL in 
the pivotal 13-week monkey toxicity study was the highest dose tested, 200 mg/kg/week 
(IV), with Cmax and Cav exposures of 10200 µg/mL and 6310 µg/mL, respectively. 
 
Staining of neuroendocrine cells with PF-07242813 in the human pituitary was observed in 
the TCR study. However, the risk of pituitary toxicity is considered low since CD1a is not 
expected to be expressed in the pituitary, PF-07242813 does not have effector function, and 
no toxicity was observed in the 13-week repeat-dose monkey study for other tissues that 
showed positive staining in the TCR study. 
 
The in vitro cytokine release assay identified the potential for PF-07242813 to induce 
cytokine release; however, the clinical translation of findings from this assay has not been 
established. 
 
The nonclinical program supports the progression of PF-07242813 in clinical trials of up to 
3 months in duration via the SC and/or IV routes of administration. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 32 
 
 
CCI 
2.2.1.3. Nonclinical PK 
Non-linear PK was observed after a single IV dose in cynomolgus monkeys, consistent with 
TMDD. In the pivotal repeat-dose GLP study, there were no apparent sex-related differences 
in systemic exposure (as assessed by Cmax and AUC), and systemic exposure increased with 
increasing dose and was higher after repeat dosing. 
 
 
The PK of PF-07242813 in humans are expected to be the same as those of a typical 
therapeutic IgG mAb. Based on a site of action PK/PD model, the predicted efficacious dose 
of PF-07242813 in humans is 30 mg SC Q4W. The predicted steady-state human AUCtau for 
the efficacious dose level is 1730 µg•h/mL and the predicted Cmax and Cav values are 
3.67 and 2.58 µg/mL, respectively. 
CCI 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 33 
 
 
 
 
 
 
 
2.2.2. Clinical Overview 
PF-07242813 has not been administered to humans. Therefore, there are no clinical safety 
data. 
 
2.3. Benefit/Risk Assessment 
Study C4461001 is the first time that PF-07242813 will be administered to humans. For 
healthy participants participating in this single and multiple doses, no clinical benefit is 
expected. The purpose of the study is to provide the basis for further clinical development of 
PF-07242813 as a potential new, pharmacological agent for the treatment of participants with 
AD. As to date, no specific human risks have been identified; postulated risks based on 
nonclinical studies are summarized in Section 2.2.1. The clinical impact of these potential 
risks will be minimized through the proposed cautious dose. The clinical impact of these 
potential risks will be minimized through the proposed cautious dose escalation process 
wherein higher doses of PF-07242813 will be administered only after lower doses have been 
found to be well tolerated with an acceptable safety profile. In addition, this study includes 
standard, intensive, inpatient monitoring of the participants following administration of 
single and multiple doses of the study intervention. 
 
The risk assessment for study participation and potential risks of PF-07242813 is provided 
below. More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of PF-07242813 may be found in the Investigator’s Brochure, 
which is the SRSD for this study. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 34 
 
 
 
2.3.1. Risk Assessment 
 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020) 
Page 35 
 
 
 
Study Procedures 
CCI 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 36 
 
 
2.3.2. Benefit Assessment 
No clinical benefit is anticipated for healthy participants. However, participants may benefit 
society by contributing to the process of developing new therapies in an area of unmet need. 
Additionally, participants will benefit from Medical evaluations/assessments associated with 
study procedures (eg, physical exam, ECG, labs, etc.). 
 
Similarly, while no clinical benefit may be expected for participants with AD, they may 
obtain potential benefit of receiving study intervention during study duration that may have 
clinical utility. 
 
2.3.3. Overall Benefit/Risk Conclusion 
Based on the preclinical toxicology studies, measures taken to minimize risk to participants 
in this study, and the ultimate potential benefit of PF-07242813 to patients with AD, the 
overall potential benefit/risk of PF-07242813 is favorable. 
 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
3.1. Objectives and Endpoints: Part 1 (Healthy Adult Participants) 
 
CCI 
PF-07242813 serum exposure as data permit: AUClast, 
AUCinf, Cmax, Tmax and t1/2 after single doses; AUCτ, 
Cmax, and Tmax after each repeated dose; and t1/2 after the 
last repeated dose. 
To characterize the serum exposure of 
PF-07242813, following single and multiple 
doses in healthy adults. 
Secondary: 
Secondary: 
Incidence of treatment-emergent adverse events (AEs 
and SAEs); vital signs, safety laboratory tests, cardiac 
telemetry (SAD only), and ECG. 
To evaluate the safety and tolerability of 
PF-07242813, following single and multiple 
doses in healthy adults. 
Primary: 
Primary: 
Endpoints 
Objectives 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 37 
 
 
3.2. Objectives, Endpoints and Estimands: Part 2 (Atopic Dermatitis Participants) 
 
Objectives 
Endpoints 
Estimands 
Primary: 
Primary: 
Primary: 
To evaluate the safety and 
tolerability of PF-07242813 
versus placebo, in participants 
with moderate to severe AD. 
Incidence of treatment-emergent 
adverse events (AEs and SAEs); 
vital signs, safety laboratory tests, 
and ECG. 
There is no defined estimand for 
these endpoints; they will be 
analyzed using CaPS as applicable. 
Secondary: 
Secondary: 
Secondary: 
To compare the efficacy of 
PF-07242813 versus placebo on 
percent change from baseline in 
Eczema Area and Severity Index 
(EASI) in participants with 
moderate to severe 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 study intervention on a 
continuous endpoint; without 
prohibited medications during 
treatment. 
Study Intervention: PF-07242813 
or placebo. 
Population: Participants with 
moderate to severe AD as defined 
by the inclusion and exclusion 
criteria. 
Variable: Percent change from 
baseline in EASI total score at 
Week 6. 
Intercurrent Events: 
a. 
Prohibited medications – all 
scores in participants who 
receive prohibited medication 
post randomization to 
Week 6 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 study 
intervention. 
b. Inadequate compliance – 
participants data will be used 
as recorded. 
Events a and b are stated with 
precedence in descending order. 
Population level summary: 
The percent change from baseline 
mean difference between 
PF-07242813 and placebo in EASI 
score. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 38 
 
 
Objectives 
CCI 
 
Endpoints 
Estimands 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 39 
 
 
Objectives 
Endpoints 
Estimands 
 
 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 40 
 
 
 
 
 
 
 
4. STUDY DESIGN 
4.1. Overall Design 
This is a first-in-human (FIH) study of PF-07242813 that will be conducted in 2 parts: Part 1 
will be conducted in healthy adult participants and Part 2 will be conducted in adult 
participants with moderate to severe AD (see Figure 1). 
 
Up to approximately 145 participants will be randomized to the study: in Part 1, up to 
approximately 57 healthy participants in SAD (including 5 Japanese participants), up to 
approximately 40 healthy participants, including an optional cohort in MAD, and in Part 2 up 
to 48 participants with moderate to severe AD. 
 
4.1.1. Part 1: Single and Multiple Ascending Dose in Healthy Participants 
Part 1 is within-cohort randomized, participant- and investigator- blind, sponsor-open, and 
placebo-controlled investigation of the safety, tolerability, PK, and immunogenicity 
following SAD and MAD of PF-07242813. 
 
Approximately 97 healthy adult participants will be enrolled at a single study site into the 
proposed cohorts listed below. Participants may only participate in one cohort. 
 
Participants in the single dose cohorts will be randomized sequentially as follows: 
 
• Cohort 1 (n=4): 0.3 mg active (n=2) or placebo (n=2), IV; 
• Cohort 2 (n=4): 1 mg active (n=2) or placebo (n=2), IV; 
• Cohort 3 (n=4): 3 mg active (n=2) or placebo (n=2), IV; 
• Cohort 4 (n=8): 10 mg active (n=6) or placebo (n=2), IV; 
• Cohort 5 (n=8): 30 mg active (n=6) or placebo (n=2), IV; 
• Cohort 6 (n=8): 100 mg active (n=6) or placebo (n=2), IV; 
• Cohort 7 (n=8): 300 mg active (n=6) or placebo (n=2), IV; 
• Cohort 8 (n=8): 1000 mg active (n=6), or placebo (n=2), IV. 
Participants in the multiple dose cohorts, will be randomized as follows: 
Estimands 
Endpoints 
Objectives 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 41 
 
 
• Cohort 10 (n=8): 15 mg active (n=6) or placebo (n=2), SC x 3 doses Q2W; 
• Cohort 11 (n=8): 50 mg active (n=6) or placebo (n=2), SC x 3 doses Q2W; 
• Cohort 12 (n=8): 150 mg active (n=6) or placebo (n=2), SC x 3 doses Q2W; 
• Cohort 13 (n=8): 300 mg active (n=6) or placebo (n=2), SC x 3 doses Q2W; 
• Cohort 14 (n=8, optional): ≤1000 mg IV active (n=6) or placebo (n=2), SC x 3 doses 
Q2W. 
 
The Japanese Participant Cohort will be randomized as follows: 
 
• Cohort 15 (n=5): a single IV dose active (n=4) or placebo (n=1). 
Within 28 days of successful completion of the screening process, eligible participants will 
be randomized to receive a single IV infusion of PF-07242813 or placebo. In order to 
mitigate any unanticipated acute safety risks within the IV infused SAD cohorts, sentinel 
dosing will be implemented in all SAD cohorts (ie, cohorts where the dose being tested is the 
highest administered in the study to date). For sentinel dosing, the first 2 participants 
(1 active: 1 placebo) will be dosed prior to the remaining participants in the cohort and 
monitored for at least 24 h to assess safety. If the dose level for the first 2 sentinel 
participants is determined to have an acceptable safety and tolerability profile, as judged by 
the investigator, the remaining participants within the cohort will be dosed. Single dose 
cohorts will be enrolled sequentially in a dose escalating fashion starting from the lowest 
proposed dose (0.3 mg). During the SAD period, escalation to subsequent dose levels will 
occur following the sponsor’s review of available safety through study Day 8 and PK data 
through Day 3 for the previous cohort. There will be a minimum of 10 days between cohorts 
for dose escalation. Dosing in this part (up to the maximum dose of 1000 mg IV) may be 
adjusted depending upon the actual exposure of PF-07242813 observed in humans at lower 
doses. If, based on the observed data, the subsequent dose projected group mean Cmax is 
>1020 µg/mL or AUC168H >106000 µg.h/mL, the exposure limits determined as 1/10th of the 
mean exposures observed at NOAEL in the 13-week cynomolgus monkey toxicity study, that 
dose will not be explored. 
 
Participants will be admitted into the clinic approximately 1 day prior to dosing and be 
required to stay overnight in the study center through completion of Day 5 evaluations. 
Participants in the single dose cohorts will return for outpatient visits per the Schedule of 
Activities (Table 1), up to Day 71 visit (or at least 4 half-lives of PF-07242813 based on 
observed data). For Cohort 1, the outpatient visit is up to Day 29 (±3 days). For Cohorts 2 
and 3, the final out-patient visit will be determined based on emerging safety and PK data 
from previous cohort(s). As such, the final scheduled visit may be earlier than Day 71 
(±3 days), but will be at least through Day 29 (±3 days). 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 42 
 
 
Four (4) multiple SC dose cohorts of PF-07242813 (15 mg to 300 mg) and 1 optional 
multiple IV dose cohort in healthy participants are planned. Initiation of the multiple dose 
(Cohort 10) will occur following the Sponsor’s review of available safety data through study 
Day 8 and PK data through study Day 3 from Cohort 6 (100 mg single IV dose) and the 
accumulated safety from the previous single dose cohorts. The starting dose of 15 mg for the 
initial multiple dose cohort may be adjusted, based on emerging safety and PK data from the 
single dose cohorts. Progression to the next multiple dose may proceed after review of: 
 
• Safety/tolerability data through Day 8 and PK data through Day 3 of the single dose 
that is no lower than the planned SC dose in next MAD cohort; 
 
• Cumulative safety and PK data from the previous single dose cohorts; 
• Safety/tolerability data through Day 22 (7 days following the 2nd dose) of the ongoing 
MAD cohort and previous MAD cohorts with lower doses. 
 
If, based on the observed data, the subsequent dose in next cohort projected group mean 
Cmax is >1020 µg/mL or AUC168H >106000 µg.h/mL µg/mL following the 3rd dose, that dose 
will not be explored. The 5th MAD cohort (Cohort 14) is optional for further investigation of 
multiple doses as needed. The dose level for this cohort will be determined following a 
review of the cumulative safety and PK data up to 1000 mg IV single dose cohort and at least 
through Day 22 (7 days following the 3rd dose) of the ongoing 300 mg MAD cohort. The 
dose in this cohort will be no more than 1000 mg IV. 
 
Healthy participants who are enrolled into the multiple dose cohorts will be randomized to 
receive PF-07242813 or placebo every 2 weeks (Q2W) for a total of 3 doses. Participants 
will be confined to the clinical research unit starting on the day prior to dosing and through at 
least 96 hours after the first dose of study intervention and 48 hours after the second and third 
doses. Participants may remain in house longer at the discretion of the PI due to operational 
logistics. Participants will return for outpatient visits per the (Table 2), at least through 
Day 99 visit (or at least 4 half-lives of PF-07242813 based on observed data). Based on 
emerging PK data, additional samples may be added to ensure PK is adequately 
characterized. Based on emerging data from previous and ongoing single and multiple dose 
cohorts, doses planned may be modified and other doses and/or dosing regimens (eg, Q4W) 
may be explored. If the exposures in the subsequent dose is projected to exceed the exposure 
limits pre-specified, after repeat doses, that dose will not be explored. 
 
In addition, a cohort of healthy Japanese adults (Cohort 15, n=5) will be enrolled to receive a 
single IV administration of PF-07242813 or placebo (4 on PF-07242813 and 1 on placebo). 
This cohort will be initiated after single dose escalation in healthy participants (SAD) is 
complete and will enroll in parallel to Part 2. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 43 
 
 
4.1.2. Part 2: Participants with Atopic Dermatitis 
Part 2 is a randomized, participant- and investigator-blind, sponsor-open, placebo-controlled 
investigation of the safety, tolerability, PK, and pharmacodynamics (including effects on 
clinical signs and symptoms) of PF-07242813 in adult participants with moderate to severe 
atopic dermatitis (AD). 
In Part 2, Cohort 9 will randomize (2:1, PF-07242813) 24 participants at the MTD defined in 
Part 1 (or maximum dose studied in Part 1 if MTD is not achieved) for the assessment of the 
safety, tolerability, PK, and clinical effects of PF-07242813 in AD and CCI 
 
. The number of participants enrolled in 
Cohort 9 will provide a sample size sufficient for statistical evaluation of the primary 
efficacy endpoint (placebo-corrected percent change from baseline in continuous EASI). 
Cohort 9 will be initiated following completion of all single dose cohorts evaluated in 
Part 1 and review of cumulative safety and PK data from Part 1. Participants in Cohort 9 will 
receive the study intervention on Day 1 at the MTD identified in Part 1, or the highest dose 
studied in Part 1 if MTD is not achieved. The dose will be administered at the clinical site, 
and participants will return for outpatient visits per the Schedule of Activities (Table 3), up to 
Week 16. 
An optional cohort (Cohort 16) of up to 24 moderate to severe AD participants may be 
enrolled as needed to evaluate further IV or SC dosing, based on cumulative safety and PK 
data from Part 1 and Cohort 9 in Part 2. 
4.2. Scientific Rationale for Study Design 
Study C4461001 represents the first time PF-07242813 will be administered to humans. 
Therefore, this first-in-human (FIH) study will employ an escalating dose design initially 
using single doses and then, once the safety and tolerability of higher single dose has been 
demonstrated, repeat doses. Study C4461001 will consist of 2 parts. Part 1 will be conducted 
in healthy participants; Part 2 will be conducted in participants with moderate to severe AD. 
 
Human reproductive safety data are not available for PF-07242813, but there is no suspicion 
of human teratogenicity based on the intended pharmacology of the compound. Therefore, 
the use of a highly effective method of contraception is required (see Appendix 4). 
 
4.2.1. Study Design Rationale for Part 1 
As PF-07242813 is projected to have the PK profile of a typical mAb, the single dose phase 
of Study C4461001 will be initiated with a dose estimated to have little pharmacologic 
activity (see dose rationale, Section 4.3.2, below) with dose escalation continuing until a 
maximally tolerated dose is identified or a dose of 1000 mg is achieved. The 1000 mg dose is 
predicted to provide >99% target coverage at maximal exposures, thereby assuring an 
adequate test of pharmacology in Part 2. The MAD phase of the study will be initiated once 
adequate safety data are available from a higher dose in the SAD phase of the study (see 
Section 4.1.1). Study C4461001 uses a placebo-controlled, blinded design to minimize bias 
which is justified in this early clinical study to provide a reference for safety and tolerability. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 44 
 
 
The dose escalation will be conducted in healthy participants (as defined by the 
inclusion/exclusion criteria) in order to establish the safety and tolerability of PF-07242813 
prior to exposure in patient populations. Both adult male and female participants are eligible 
for enrolment in the study provided females are confirmed either to be of non-childbearing 
potential or, if of childbearing potential, to be using a nonhormonal form of highly effective 
contraception of low user dependency (such as an intrauterine device or surgical sterilization 
as stipulated in Appendix 4: Contraceptive Guidance). No barrier method of contraception 
(eg, condom) is warranted for male participants as the potential exposure to PF-07242813 via 
semen to partners of male participants is anticipated to be very low, as the calculated safety 
margin between the estimated maternal exposure due to seminal transfer at maximum 
dose/exposure proposed in human and the minimal anticipated biological effect level 
(MABEL) of PF-07242813 is in excess of 100-fold. Additionally, PF-07242813 does not 
have genotoxicity concerns. If emerging human PK in this study suggests the potential 
exposure of PF-07242813 to the partners of male participants via semen could exceed 
anticipated MABEL exposures at the highest proposed doses, male condom will be required 
for the following cohorts. As an additional safety measure, WOCBP will be required to have 
a negative pregnancy test prior to randomization and at pre-specified visits per the Schedule 
of Activities. 
 
Healthy Japanese participants will be enrolled in a separate cohort to provide a preliminary 
characterization of the safety, tolerability, and PK profile of PF-07242813, to support 
potential inclusion of Japanese patients in future studies. 
 
Risks to study participants will be minimized by cautious dose escalation in an inpatient 
setting, with careful assessment and ongoing review of emerging safety data. Given that the 
overall potential risk of immunogenicity with PF-07242813 has been assessed to be moderate 
and that the cytokine release assay has suggested a low potential for cytokine release 
syndrome (Section 2.2.1), sentinel dosing will be implemented in all SAD cohorts 
(ie, cohorts where the dose being tested is the highest administered dose in the study to date). 
Sentinel dosing will involve administration of PF-07242813 or placebo to the first 
2 participants randomized as 1: 1 in each SAD cohort, with observation for at least 24 hours 
to establish adequate safety and tolerability before dosing the remaining participants in the 
cohort. 
 
Together, the implementation of sentinel dosing in SAD cohorts and the dose escalation rules 
(Section 6.6.1) are expected to minimize the risk to study participants while providing key 
safety and tolerability information. As is standard for FIH studies, dose administration will 
be conducted in the fasting state in order to facilitate management of any adverse events that 
may occur shortly after dosing. 
 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 45 
 
 
associated safety concern at the last scheduled visits eg, Day 99 visit (~70 days after 3rd dose) 
 
 
Staining of neuroendocrine cells with PF-07242813 in the human anterior pituitary was 
observed in a tissue cross reactivity study that was not observed in the homologous 
cynomolgus monkey tissues (Section 2.2.1). The overall risk of pituitary toxicity in humans 
is considered low; however selected anterior pituitary hormones and hormones regulated by 
them will be monitored in SAD/MAD cohorts as a screen for potential adverse effects on the 
pituitary gland. 
 
Currently, the final scheduled out-patient visits in SAD and MAD cohorts (except 
Cohorts 1-3 in SAD) are planned to be approximately 70 days after last dose, which is 
>4 times of PF-07242813 t1/2 predicted in human (17 days). Based on emerging data, the last 
out-patient visit schedule may be modified in the following cohorts to cover at least 
4 half-lives of PF-07242813 observed in previous cohorts. 
 
4.2.2. Study Design Rationale for Part 2 
The objectives of Part 2 of Study C4461001 are to assess the safety and tolerability of 
PF-07242813 at a single maximally planned or maximally tolerated dose in participants with 
moderate to severe AD, and to provide preliminary data on the effects of PF-07242813 on 
clinical signs and symptoms of AD. 
 
Part 2 of Study C4461001 will consist of up to 2 cohorts of participants with moderate to 
severe AD (Cohorts 9 and optional Cohort 16). Participants in Cohort 9 will receive a single 
IV dose of study intervention at the MTD established in Part 1 (or the highest dose studied in 
Part 1 if MTD is not achieved). The sample size of approximately 24 participants with AD in 
Cohort 9 will support the assessment of clinical activity for the primary efficacy endpoint. 
This approach is justified by the accumulated single and available multiple dose safety data 
generated in the healthy participants, and the extended duration of high target occupancy 
predicted at this dose. 
 
The optional Part 2 cohort (Cohort 16) would allow for further investigation of the safety, 
tolerability, PK, and pharmacodynamics of PF-07242813 at lower or repeat doses, as deemed 
necessary based on emerging data. As for Part 1, Part 2 of Study C4461001 will be blinded to 
the site personnel (with the exception of the site pharmacist and, as needed, an individual 
designated to administer study intervention who is not otherwise associated with the study) 
and placebo-controlled, with the same rationale. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 46 
 
 
As noted above, a secondary objective of Part 2 is to evaluate the potential clinical activity of 
PF-07242813 in patients with moderate to severe AD in order to guide future development of 
the molecule. The patient population defined by the inclusion/exclusion criteria, the predicted 
human PK profile, and the resultant predicted level and duration of target engagement is 
expected to provide an adequate test of the pharmacology of PF-07242813 in inhibiting 
CD1a proinflammatory signaling in AD. The sample size and randomization schemes is 
expected to be sufficient to detect clinically meaningful improvement in AD signs and 
symptoms (see Section 9.2.2). 
 
Women of childbearing potential (WOCBP) will be eligible for participation if they agree 
and adhere to the contraception guidelines stipulated in this protocol 
(Appendix 4: Contraceptive), which include hormonally based contraception methods. 
Although reproductive safety data are not available for PF-07242813, there is no suspicion of 
human teratogenicity, genotoxicity, or clastogenicity based on the pharmacology of the 
compound that would preclude the inclusion of WOCBP using highly effective contraception 
into a controlled clinical trial. Compared to the contraception requirements in Part 1, the 
allowance for hormonal methods of contraception is justified by the accumulated safety and 
tolerability data from the SAD and MAD cohorts in Part 1 and will facilitate recruitment 
given that many patients with AD are of reproductive age and capacity. As an additional 
safety measure, WOCBP will be required to have a negative pregnancy test prior to 
randomization and at all study visits. 
 
For both Part 1 and Part 2, Banked Biospecimens will be collected and stored for further 
analyses which may, for example, provide greater understanding of the study intervention. 
 
4.3. Justification for Dose 
4.3.1. Prediction of Human PK and Efficacious dose 
Based on the serum PK parameter values observed for PF-07242813 in nonclinical species, 
the predicted 2-compartment PK parameter values in humans are expected to be the same as 
those of a typical therapeutic IgG mAb. These values have been reported previously (Dirks 
and Meibohm 2010; Betts et al. 2018)8,2 and were used for the PF-07242813 human PK 
predictions as follows: 3.2 L for central volume, 2.2 L for peripheral volume, 0.25 L/day for 
central CL, 0.45 L/day for distributive clearance, 0.26 1/day for SC absorption rate constant 
and 60% for SC bioavailability. The predicted volume and clearance values resulted in a 
17-day t½ and a 5.4 L Vss. 
 
As there are no validated mechanism-based biomarkers or preclinical disease/efficacy model 
for human AD, the efficacious dose of PF-07242813 has been projected empirically, as a 
dose that will achieve >95% CD1a receptor occupancy at steady state trough concentrations 
at the site of action (skin). A site of action model was used to link PF-07242813 exposure to 
CD1a receptor occupancy using the PF-07242813 KD and the predicted human PK 
parameters, CD1a concentrations in skin and CD1a internalization/turnover rate. Using this 
approach, the predicted efficacious human dose of PF-07242813 is estimated to be 30 mg SC 
q4wk. The projected steady state AUCtau (tau=4 weeks/672 hrs), Cave and Cmax associated 
with the predicted efficacious dose are 1730 µg.h/mL, 2.58 µg/mL and 3.67 µg/mL. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 47 
 
 
4.3.2. Dose Rationale for Part 1 
The nonclinical safety profile of PF-07242813 has been adequately characterized to support 
development into human clinical studies of up to 3 months in duration. No test article-related 
effects or target organs were identified following once weekly administration of 
PF-07242813 in a pivotal 13-week cynomolgus monkey toxicity study with the NOAEL 
defined as the highest dose tested, 200 mg/kg/week (IV). In this study, the Cmax and AUC168H 
exposure limit for dose escalation are set to be 1020 µg/mL and 106000 µg/mL, respectively, 
determined as 1/10th of the mean exposures observed at NOAEL in the monkey toxicity 
study. 
 
A starting dose of 0.3 mg PF-07242813 IV is planned. The predicted PF-07242813 Cmax and 
AUC168H at the 0.3 mg single dose are approximately 10890-fold and 11150-fold, 
respectively, below the exposure limits pre-defined for PF-07242813 dose escalation (see 
Table 4). The predicted exposures at the 0.3 mg single dose are approximately 39- and 
82-fold below the steady-state exposure at projected efficacious dose (30 mg SC Q4W) for 
Cmax and AUCtau (tau=4 weeks/672 hrs), respectively. The maximum CD1a receptor 
occupancy at skin, the site of action after 0.3 mg IV single dose is predicted to ~29%, at 
which level little pharmacological effect is expected as PF-07242813 is an antagonist of 
CD1a target engagement. The starting dose selection is consistent with the EMA guideline on 
first-in-human study (EMA Guideline on strategies to identify and mitigate risks for 
first-in-human and early clinical trials with investigational medicinal products) and a recent 
white paper on FIH starting dose selection by the IQ consortium (Leach et al. 2020).14 The 
highest proposed IV infusion dose of 1000 mg is estimated to provide an exposure margin of 
3.3-fold for both Cmax and AUC168H, relative to the exposure limits. 
 
Table 4. 
Projected Exposures, Maximum CD1a Receptor Occupancy and Safety 
Margins Following Single IV Doses of PF-07242813a 
 
DOSE 
(mg) 
Cmax 
(µg/mL) 
AUC 
168H 
(µg·h/mL) 
SM_Cma b 
x 
(fold) 
SM_AUCb 
(fold) 
ROc 
(%) 
0.3 
0.09368 
9.51 
10890 
11150 
29.3 
1 
0.3111 
31.65 
3279 
3349 
59.2 
3 
0.9332 
94.95 
1093 
1116 
81.2 
10 
3.111 
316.5 
328 
335 
93.8 
30 
9.332 
949.5 
109 
112 
97.9 
100 
31.11 
3165 
33 
33 
99.4 
300 
93.32 
9495 
11 
11 
99.8 
1000 
311.1 
31650 
3.3 
3.3 
99.9 
a. Human PK was predicted using 2-CM model with IV infusion and linear PK. For dose <1 mg, infusion over 10 min, 
otherwise, infusion over 1 hour. Vc=3.2 L, Vp=2.2 L, CL=0.25 L/day, Q= 0.45 L/day. For dose <1 mg, it is assumed 
that infusion over 10 min, otherwise, infusion over 1 hour. 
b. SM= safety margin, which is calculated relative the exposure limit (Cmax = 1020 µg/mL and 
AUC168H=106000 µg.h/mL), determined as 1/10th of the mean exposure at NOAEL of 200 mg/kg/week IV in pivotal 
13-week cynomolgus monkey toxicity study. 
  c. A site of action model was used to predict CD1a receptor occupancy at skin with the predicted human PK. 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 48 
 
 
 
The dose range of 15 mg to 300 mg SC administered every two weeks (Q2W) in total of 
3 doses were selected for dose escalation in 4 MAD cohorts (Table 5). The dosing regimen of 
every two weeks (Q2W) was selected to achieve high exposures of PF-07242813 with fewer 
doses compared to monthly dosing for adequate safety assessment. The multiple dose period 
is planned to be initiated at the 15 mg SC dose level with the Cmax and AUC168H following 
3 repeated doses, each dose predicted to be 424- and 287-fold below the exposure limits 
pre-defined. The predicted exposures following 3 repeated doses at 15 mg SC are also below 
the steady-state exposures at projected efficacious dose (30 mg SC Q4W) for both Cmax 
(2.405 vs 3.67 µg/mL) and AUCtau (1144 vs 1730 µg.h/mL over 4 weeks/672 hrs). At the 
highest dose proposed (1000 mg IV) in an optional MAD cohort, the predicted margins for 
Cmax and AUC168H, relative to the exposure limits, are 2.3- and 2.1-fold, respectively 
(Table 5). 
 
Table 5. 
Projected Exposures, Maximum CD1a RO and Safety Margins After the 3rd 
Dose of Multiple SC or IV Doses of PF-07242813a 
 
DOSE 
(mg q2wk)b 
Cmax 
(µg/mL) 
Tmax 
(hr) 
AUC 
168H 
(µg·hr/mL) 
C c 
ave 
(µg/mL) 
SM_C d 
max 
(fold) 
SM_AUCd 
(fold) 
SM_C d 
ave 
(fold) 
Max ROe 
(%) 
15 
2.405 
96 
369.4 
2.092 
424 
287 
302 
96.3 
50 
8.017 
96 
1231 
6.973 
127 
86 
91 
98.7 
150 
24.05 
96 
3694 
20.92 
42 
29 
30 
99.6 
300 
48.1 
96 
7388 
41.84 
21 
14 
15 
99.8 
1000 IV 
441.6 
1 
50640 
245 
2.3 
2.1 
2.6 
99.9 
a. Human PK was predicted using 2-CM model with S.C. in which Vc=3.2 L, Vp=2.2 L, CL=0.25 L/day, Q=0.45 L/day, 
0.26 1/day for SC absorption rate constant and 60% for bioavailability were used. PK parameters after the 3rd dose are 
presented. 
b. Dose is given q2wk with 3 doses in total. All the doses are given as subcutaneously except 1000 mg which is given 
IV over 1 hr infusion. 
c. Cave=AUCtau/336 (tau=336 hours for q2wk dosing in MAD cohorts). 
d. SM=safety margin, which is calculated relative the exposure limits of Cmax=1020 µg/mL and 
AUC168H=106000 µg.h/mL, determined as 1/10th of the mean exposure at NOAEL of 200 mg/kg/week IV in pivotal 
13-week cynomolgus monkey toxicity study. Cave used for safety margin calculation is exposure limit of AUC168H 
divided by 168 hr. 
e. A site of action model was used to predict CD1a receptor occupancy at skin with the predicted human PK. 
 
4.3.3. Dose Rationale for Part 2 
A single dose of study intervention is planned in 24 adult participants with AD (Cohort 9), at 
the maximum tolerated dose (MTD) observed in Part 1 or the highest dose studied in Part 1 if 
MTD is not achieved (eg, the planned maximum dose of 1000 mg). Following a 1000 mg 
single IV dose of PF-07242813, the predicted CD1a receptor occupancy would be saturated 
and remain high (>95%) for greater than 16 weeks. An optional cohort (Cohort 16) may be 
used to evaluate further IV or SC dosing of PF-07242813, based on cumulative safety and 
PK data from Part 1 and Cohort 9 in Part 2. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 49 
 
 
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 End-of-Study visit. 
 
The end of the study is defined as the date of the last visit of the last participant in the study. 
 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
 
Age and Sex: 
 
1. Part 1 only: Adult male or female participants between 18 to 55 years of age, 
inclusive, at the time of signing the ICD. 
 
• Refer to Appendix 4 for reproductive criteria for males (Section 10.4.1), females 
of non-child bearing potential (Section 10.4.2), and females of child-bearing 
potential (Section 10.4.3). 
 
OR 
 
Part 2 only: Male or female participants, who at the time of screening, are between the 
ages of 18 and 65 years, inclusive. 
 
• Refer to Appendix 4 for reproductive criteria for male participants 
(Section 10.4.1), females of non-child bearing potential (Section 10.4.2), and 
females of child-bearing potential (Section 10.4.3). 
 
Type of Participant and Disease Characteristics: 
 
2. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, and other study procedures. 
 
3. Part 1 only: Participants who are overtly healthy as determined by medical 
evaluation including medical history, physical examination, vital sign assessments, 
temperature, 12-lead ECGs, laboratory tests. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 50 
 
 
4. Part 1, Japanese cohort: Healthy adults of Japanese descent, where parents and 
grandparents are Japanese. 
 
5. Part 2 only: Must meet the following atopic dermatitis criteria: 
 
a. Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic 
eczema) for approximately 1 year prior to Day 1 and have the diagnosis of AD 
confirmed (Hanifin and Rajka criteria of AD).10 
b. Either have had an inadequate response to treatment with topical medications (for 
at least 4 consecutive weeks within 1 year of the first dose of the study drug). 
 
OR 
 
Have a documented reason why topical treatments are considered medically 
inappropriate (eg, because of important side effects or safety risks) within the last 
year. 
 
c. Have moderate to severe AD (defined as having an affected BSA (captured as 
part of EASI) ≥10%, IGA ≥3, and EASI ≥12 at both the screening and baseline 
visits). 
 
d. Have an otherwise healthy medical evaluation (other than signs and symptoms of 
AD) including medical history, physical examination, vital sign assessments, 
temperature, 12-lead ECGs, laboratory tests. 
 
Note: Controlled comorbid diseases (ie, controlled diabetes not requiring insulin, 
controlled hypertension), are acceptable, so long as they do not require 
administration of prohibited medications. 
 
e. Mild or moderate asthma that is well-controlled (not requiring high dose inhaled 
corticosteroids, systemic [oral or parenteral] corticosteroids, or biologic asthma 
treatments). 
 
Weight: 
 
6. Part 1: BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs); 
Part 2: BMI of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lbs). 
Informed Consent: 
 
7. 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 51 
 
 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
 
Medical Conditions: 
 
1. Evidence of active, latent, or inadequately treated infection with Mycobacterium 
tuberculosis (TB) as defined by both of the following: 
 
a. A positive QuantiFERON-TB Gold In-tube or equivalent test. 
 
b. History of either untreated or inadequately treated latent or active TB infection, or 
current treatment for the same. 
 
2. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, 
hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or 
hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. As an exception a 
positive HBsAb test due to hepatitis B vaccination is permissible. 
 
Testing for SARS-CoV-2 will be at the discretion of the investigator, based on local 
infection rates, patient exposure history, and reported signs or symptoms of 
COVID-19. 
 
3. 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. 
 
• Part 2 only: At Screening Visit, if there are “yes” answers on items 4, 5 in the 
past year or on any question in the suicidal behavior section of the 
Columbia-Suicide Severity Rating Scale (C-SSRS) in the past 6 months, the 
participant will not be included in the study. 
 
4. Known history of or evidence of current endocrine disease. 
 
5. Have a history of systemic infection requiring hospitalization, parenteral 
antimicrobial therapy, or as otherwise judged clinically significant by the investigator 
within 6 months prior to Day 1. 
 
6. Recent exposure to live or attenuated vaccines within 28 days of the screening visit. 
 
7. Have any malignancies or have a history of malignancies with the exception of 
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the 
skin, or cervical carcinoma in situ. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 52 
 
 
8. Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) 
related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and 
symptoms suggestive of current lymphatic or lymphoid tissue disease. 
 
9. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, 
immunological/rheumatological. 
 
10. Part 1 only: allergic disease (including drug allergies, but excluding untreated, 
asymptomatic, seasonal allergies at the time of dosing). 
 
Additional Exclusionary Medical Criteria for Part 2 (Atopic Dermatitis Cohorts) 
 
11. Part 2: Currently have active forms of other inflammatory skin diseases. 
 
12. Part 2: Have history of or current evidence of skin conditions (eg, psoriasis, 
seborrheic dermatitis, lupus) at the time of Day 1 that would interfere with evaluation 
of atopic dermatitis or response to treatment. 
 
13. Part 2: Have active chronic or acute skin infection requiring treatment with systemic 
antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks 
prior to Day 1, or superficial skin infections within 1 week prior to Day 1. 
NOTE: potential participants may be rescreened after infection resolves. 
 
14. Part 2: Score of >5 on the Fitzpatrick Skin Type Assessment. 
 
15. Part 2: History of anaphylaxis with the following exceptions: participants with 
sensitivity and/or anaphylaxis only to a single, avoidable allergen (eg, aspirin, 
penicillin, sulfadrugs, nonsteroidal anti-inflammatory drugs [NSAIDs], peanuts) may 
be enrolled, if in the opinion of the investigator, the participant is aware of the 
hypersensitivity and avoids -the problematic allergen. Participants must carry 
appropriate treatment for anaphylaxis and must know how to manage anaphylactic 
reactions. 
 
Prior/Concomitant Therapy: 
 
16. Participation in any other cohort of this study: participants can only be randomized 
once into this study and be assigned to 1 cohort only. 
 
17. Have undergone significant trauma or major surgery within 1 month of the first dose 
of study drug. 
 
18. Part 1 only: Use of prescription or nonprescription drugs and dietary and herbal 
supplements within 7 days or 5 half-lives-(whichever is longer) prior to the first dose 
of PF-07242813. (Refer to Section 6.5.1 for additional details). 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 53 
 
 
19. Part 2 only: Have received any of the treatment regimens within the specified 
timeframes as outlined in Section 6.5.2.2 (Prohibited Treatments and Medications 
During the Study). 
 
Prior/Concurrent Clinical Study Experience: 
 
20. Treatment with an investigational drug within 28 days (or as determined by the local 
requirement) or 5 half-lives preceding the first dose of study treatment (whichever is 
longer). 
 
21. Part 2 only: Any investigational or experimental therapy taken or procedure 
performed for AD, psoriasis, psoriatic arthritis, rheumatoid arthritis or other 
inflammatory diseases in the previous 1 year should be discussed with the Pfizer 
Medical Monitor (or designee). 
 
Diagnostic Assessments: 
 
22. A positive urine drug test (please refer to Section 10.2). 
 
23. Part 1: Screening supine blood pressure ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic) 1 for healthy adults. 
 
Part 2: Screening supine blood pressure ≥160 mm Hg (systolic) or ≥100 mm Hg 
(diastolic), following at least 5 minutes of supine rest. 
 
For Part 1 and Part 2, if blood pressure (BP) meets the criteria above for a given 
single measurement, the BP should be repeated two more times and the average of the 
three BP values should be used to determine the participant’s eligibility. 
 
24. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, baseline 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 54 
 
 
25. 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 test, if deemed necessary: 
 
a. Part 1: AST or ALT level >1.2 × ULN; 
Part 2: AST or ALT level ≥3 × ULN 
 
b. Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ ULN. 
 
c. History or current evidence of anterior pituitary disorders Screening test results 
 
 
 
 
 
Other Exclusions: 
 
26. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 
5 (male) or 4 (female), or more alcoholic drinks in about 2 hours. As a general rule, 
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine). 
 
27. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 
 
28. History of sensitivity to heparin or heparin-induced thrombocytopenia. 
 
29. Unwilling or unable to comply with the criteria in the Lifestyle Considerations 
section of this protocol. 
 
30. 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. 
 
31. Pregnant female participants, breastfeeding female participants, male participants 
with partners currently pregnant, or male or female participants pursuing artificial 
reproductive technologies including but not limited to sperm/egg donation (see 
Section 5.3). 
 
32. Use of tobacco/nicotine containing products more than 5 cigarettes/day. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 55 
 
 
5.3. Lifestyle Considerations 
5.3.1. Meals and Dietary Restrictions 
Participants must abstain from all food and drink (except water) at least 4 hours prior to any 
safety laboratory evaluations and at least 8 hours prior to dose administration. Water is 
permitted without restriction. 
 
Part 1: The following requirements apply ONLY to Part 1, while the participants are 
confined in CRU: 
 
• Breakfast will not be provided on Day 1. 
• Noncaffeinated drinks may be consumed with meals and the evening snack. 
• Lunch will be provided approximately 4 hours after dosing on Day 1. Dinner will be 
provided approximately 9 to 10 hours after dosing on Day 1. 
 
• An evening snack may be permitted. 
• The total daily nutritional composition, while confined, should be approximately 55% 
carbohydrate, 30% fat, and 15% protein. The daily caloric intake per participant 
should not exceed approximately 3200 kcal. 
 
5.3.2. Alcohol, Caffeine and Tobacco 
• All participants will abstain from alcohol for 24 hours prior to all outpatient visits. All 
participants may undergo an alcohol breath test or blood alcohol test at the discretion 
of the investigator. Participants in Part 1 will abstain from alcohol for 24 hours prior 
to admission to the CRU and continue abstaining from alcohol during clinical 
confinement at the CRU. Participants may undergo an alcohol breath test at the 
discretion of the investigator. 
 
• All participants will abstain from caffeine-containing products for 24 hours prior to 
all outpatient visits till the completion of infusion of the IP and necessary activities 
such as ECG, vitals, respiratory rate (RR). Participants in Part 1 will abstain from 
caffeine-containing products for 24 hours prior to admission to the CRU and during 
confinement in the CRU. 
 
• All participants will abstain from the use of tobacco- or nicotine-containing products 
for 6 hours prior to all outpatient visits and through the completion of infusion of the 
IP and necessary activities such as ECG, vitals, respiratory rate (RR). Participants in 
Part 1 will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to admission to the CRU and during confinement in the CRU. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 56 
 
 
5.3.3. Activity 
• Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each study visit requiring blood 
collection for clinical laboratory tests. Walking at a normal pace will be permitted. 
 
• Part 1: Participants will be confined to the procedure room for the first 4 hours after 
dosing on Day 1 during continuous cardiac monitoring, except to use the bathroom. 
After this, if the equipment setup allows, participants may be ambulatory during the 
ECG monitoring period, but should not engage in strenuous activities. If equipment 
does not allow ambulation, appropriate accommodations will be made by the 
investigator site to facilitate continuous monitoring (eg, bedside urinals should be 
provided to accommodate participants’ excretory needs). 
 
5.3.4. Contraception 
The investigator, or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant 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 Schedule of Activities, the 
investigator or designee will inform the participant of the need to use highly effective 
contraception consistently and correctly, and document the conversation and the participant’s 
affirmation in the participant’s chart (participants need to affirm their consistent and correct 
use of at least 1 of the selected methods of contraception). In addition, the investigator or 
designee will instruct the participant to call immediately if the selected contraception method 
is discontinued or if pregnancy is known or suspected in the participant or partner. 
 
In Part 1, females of childbearing potential enrolled are required to use a low user 
dependency, nonhormonal form of highly effective contraception for contraception method 
(such as an intrauterine device or surgical sterilization, as stipulated in Appendix 4 
Section 10.4.4). 
 
5.4. Screen Failures 
Part 1: Screen failures are defined as participants who consent to participate in the clinical 
study but are not subsequently enrolled in the study. Screen failure data are collected and 
remain as source and are not reported to the clinical database. Individuals who do not meet 
the criteria for participation in this study (screen failure) may not be rescreened. However, 
for participants who have met the criteria for participation during screening but the screening 
falls outside 28-day window, they can be rescreened in this case. 
 
Part 2: 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, 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 57 
 
 
eligibility criteria, and any SAE must be documented in source and recorded in the CRF. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened twice. 
 
Delays in randomization of a participant (up to 1 week) related to receipt of primary or repeat 
laboratory results will not be considered protocol deviations. 
 
6. STUDY INTERVENTION 
Study intervention is defined as any investigational intervention, marketed product, placebo, 
medical device, or study procedure intended to be administered to a study participant 
according to the study protocol. 
 
For the purposes of this protocol, study intervention refers to PF-07242813 and placebo, 
administered either intravenously or subcutaneously. 
 
6.1. Study Intervention(s) Administered 
 
Intervention Name 
PF-07242813 
Placebo 
Type 
Active Drug 
Placebo 
Dose Formulation 
PF-07242813 100 mg/mL vial 
Vial 
Route of Administration 
IV 
SC 
IV 
SC 
Use 
Active 
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 
vials. 
Study intervention will be provided 
in vials. 
 
6.1.1. Administration 
PF-07242813 and placebo will be administered intravenously or subcutaneously. 
 
Following an overnight fast of approximately 8 hours, participants will receive study 
intervention (start time of infusion) at approximately 0800 hours (plus or minus 3 hours). For 
planned IV dosing (Cohorts 1-9 and 14), study intervention will be administered as an 
intravenous infusion over 15-30 min for dosing solution ≤10 mL and 60 min for dosing 
solution >30 mL. In the case of mild infusion reactions, at the discretion of the investigator, 
the infusion may be interrupted and restarted at a slower infusion rate not to exceed a total 
administration duration of 90 minutes. The start and stop time of the infusion will be 
recorded in source document and CRF. Time 0 is the time when the study intervention 
infusion begins. The infusion rate and amount of volume infused will be recorded. For 
Cohorts 10-13, study intervention is planned to be administered subcutaneously. Each 
injection should occur at a different site on the abdomen, approximately 1 cm apart. 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 58 
 
 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business. 
 
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual. 
 
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label. 
 
5. Study interventions should be stored in their original containers. 
 
6. Staff will instruct participants on the proper storage requirements for take-home study 
intervention. 
 
7. See the IP Manual for storage conditions of the study intervention, once diluted. 
 
8. 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). All study 
interventions will be accounted for using a study intervention accountability 
form/record. 
 
9. 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 59 
 
 
6.2.1. Preparation and Dispensing 
See the IP manual for instructions on how to prepare the study intervention for 
administration. Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance. A second staff member will verify the dispensing. 
 
Study intervention and placebo will be prepared by qualified unblinded site personnel 
according to the IP manual. The study intervention will be administered in a blinded fashion 
to the participants. 
 
6.3. Measures to Minimize Bias: Randomization and Blinding 
6.3.1. Allocation to Study Intervention 
The investigator will assign participant numbers sequentially to the participants as they are 
screened for the study. Pfizer will provide a randomization schedule to the investigator and, 
in accordance with the randomization numbers, the participant will receive the study 
treatment regimen assigned to the corresponding randomization number. It will also appear 
on the study medication containers. Study intervention will be dispensed at the study visits 
summarized in the SoA. 
 
Healthy participants will be randomized (once) into the SAD period, at which time, they will 
receive treatment assignment (PF-07242813 or placebo) for both the SAD and MAD periods. 
Participants will receive the same blinded treatment assignment (ie, the same dose level of 
PF-07242813 or placebo) throughout, in both the SAD and MAD cohorts. 
 
• The randomization ratio for the cohorts in the healthy participant SAD/MAD segment 
will be 3:1 (PF-07242813:Placebo) with the exception of Cohorts 1-3, which will be 
randomized 1:1. 
 
• The overall randomization ratio for the atopic dermatitis cohorts will be 
2:1 (PF-07242813:Placebo) for Cohort 9. 
 
Investigators, all participants and all study personnel involved in the study, with the 
exception of the pharmacist who prepares the study treatment and, as needed, an individual 
designated to administer study intervention who has no other involvement with study 
conduct, personnel, or participants, will remain blinded to each participant’s assigned study 
intervention throughout the course of the study. In order to maintain this blind, an otherwise 
uninvolved third party will be responsible for the preparation and dispensing of all study 
intervention and will endeavor to ensure that there are no differences in time taken to 
dispense or visual presentation following randomization. 
 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site to verify that randomization/dispensing has been done 
accurately. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 60 
 
 
6.3.2. Breaking the Blind 
The method for breaking the blind in this study will be manual. A sealed envelope that 
contains the study intervention assignment(s) for each participant will be provided to the 
investigator. The sealed envelope will be retained by the investigator (or representative) in a 
secured area. 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. If a participant’s treatment assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. When the 
blinding code is broken, the reason must be fully documented and entered on the CRF/DCT. 
 
Once the study is complete, all envelopes (sealed and opened) must be inventoried and 
retained until authorization for destruction has been provided. 
 
6.4. Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. 
 
The site will complete the required dosage Preparation Record located in the IP manual. The 
use of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee. 
 
6.5. Concomitant Therapy 
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All participants will be questioned about 
concomitant treatment at each clinic visit. 
 
Treatments taken within 28 days before the first dose of study investigational product will be 
documented as a prior treatment. Treatments taken after the first dose of study investigational 
product will be documented as concomitant treatments. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 61 
 
 
6.5.1. Concomitant Treatments in Part 1 
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤2.5 g/day. 
 
Females taking hormone replacement therapy may be eligible to participate in this study if 
they are willing to discontinue therapy at least 28 days prior to the first dose of study 
treatment and remain off hormonal therapy for the duration of the study. 
 
6.5.2. Concomitant Treatments in Part 2 
6.5.2.1. Permitted During Study 
Participants will be queried about concomitant medication (including topical medications and 
treatments, over-the-counter and prescription medications and treatments, and vaccinations) 
at each study visit. All concomitant treatments taken during the study must be recorded with 
indication, daily dose, and start and stop dates of administration. Any new concomitant 
medications or dose changes to current concomitant medications should be evaluated for 
potential new or worsening adverse events. 
 
Treatments taken within 28 days before the first dose of study investigational product will be 
documented as a prior treatment. Treatments taken after the first dose of study investigational 
product will be documented as concomitant treatments. 
 
The following concomitant therapies are permitted during the study: 
 
• Oral antihistamines (excluding H4 antagonists) for allergies. 
• Stable dose of leukotriene antagonists/modifiers. 
• Corticosteroid inhalers at allowed doses (exclusive of high doses of inhaled 
corticosteroids) is permitted for stable asthma. 
 
• Non-medicated emollient and sunscreen are the only topical products permitted to be 
used on atopic dermatitis skin during the study. Participants are recommended not to 
switch the emollient or sunscreen during the study. 
 
A participant who is receiving a permitted concomitant medication for any reason must be on 
a locally-approved medication and dose for the treated indication, and this must be 
documented in the CRF. Participants are not allowed any other investigational drugs or 
treatments during the study. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 62 
 
 
Participants should refrain from starting new or changing doses of permitted prescription or 
non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives 
(whichever is longer) prior to Day 1 and throughout the study, unless otherwise noted below. 
 
Acetaminophen may be used intermittently (not to exceed 2.5 g/day). Vitamin and mineral 
supplements of standard potency are allowed in amounts not known to be associated with 
adverse effects (such as hypervitaminosis). 
 
Participants should report any changes to permitted medications during the study to the 
investigator as soon as they occur. Medication changes must be documented in the 
participant’s record and CRF. 
 
Unless a prohibited medication or treatment, participants may be administered any other 
medications necessary for the treatment of concomitant medical disorders as deemed 
necessary by the treating physician. Following Day 1, addition of concomitant medications or 
any change in the dosage should be limited to those considered medically essential. 
 
6.5.2.2. Prohibited Treatments and Medications During the Study 
Participants are required to discontinue and avoid using certain medications and treatments. 
Participants should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications. Prohibited 
medications include: 
 
a. Systemic Corticosteroids: 
 
• Participants receiving systemic corticosteroids within 4 weeks prior to first dose 
of study intervention or scheduled to receive systemic corticosteroids during the 
study period for another condition. 
 
• Participants receiving doses of depot preparations of parenteral corticosteroids 
within 6 weeks of the predicted end of release of the corticosteroid from the depot 
are excluded. 
 
• An inhaled dose of greater than 1000 µg fluticasone, or an equivalent inhaled 
corticosteroid, per day. 
 
b. Leukotriene antagonists/modifiers: 
 
• Asthmatic participants taking stable doses of leukotriene antagonists/modifiers for 
at least 28 days prior to first dose of study drug may be included. 
 
c. Prior or current use of anti-IL-33 targeted therapies. 
 
d. Current or anticipated use of protein therapeutics. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 63 
 
 
e. Benralizumab within 12 months of first dose of study intervention, or at any time 
during the study. 
 
f. Prior use of the following drugs within 6 months of first dose of study intervention, or 
at any time during the study: 
 
• Prior or current use of anti-IL-4 and/or IL-13 targeted therapies (eg, lebrkizumab, 
tralokinumab). 
 
• Anti-IL-5 targeted therapies (eg, mepolizumab or reslizumab). 
• Any cell-depleting agents including but not limited to rituximab: within 6 months 
of first dose of study drug or 5 half-lives (if known), or until lymphocyte count 
returns to normal, whichever is longer. 
 
g. Prior use of dupilumab within 4 months of first dose of study intervention, or at any 
time during the study. 
 
h. Within 12 weeks of first dose of study intervention, or at any time during the study: 
 
• Other biologics: within 12 weeks of starting study intervention or 5 half-lives (if 
known), whichever is longer. 
 
i. Within 4 weeks of first dose of study intervention, or at any time during the study: 
 
• Use of oral immune suppressants (eg, cyclosporine A [CsA], azathioprine, MTX, 
Celcept, mycophenolate-mofetil, interferon-gamma (IFN-γ) within 4 weeks of 
first dose of study drug or within 5 half-lives (if known), whichever is longer. 
 
• Any Janus Kinase (JAK) inhibitors, including participation in any clinical studies 
in which a JAK inhibitor was a possible study treatment. 
 
• Investigational drugs. 
• Live, attenuated or mRNA vaccines. 
• Oral or topical phosphodiesterase (PDE) 3 or PDE4 antagonists (eg, apremilast, 
crisaborole); oral/topical histamine H4 antagonists: within 28 days or 5 half-lives 
whichever is longer prior to first dose of study drug. 
 
• Phototherapy (NB-UVB) or broad band phototherapy. 
• Regular use (more than 2 visits per week) of a tanning booth/parlor. Use of 
bronzing creams, gels or sprays within the last 2 weeks. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 64 
 
 
j. Within 1 week of first dose of study intervention, or at any time during the study: 
 
• Topical treatments that could affect atopic dermatitis (eg, corticosteroids, 
calcineurin inhibitors, tars, antibiotic creams, topical antihistamines). 
 
A protocol deviation is to be completed for any participant that takes a prohibited treatment 
or medication during the study and the sponsor is to be notified. The participant may be 
replaced at the discretion of the sponsor if prohibited treatments have been taken prior to 
Week 6. 
 
All medications and treatments that could affect atopic dermatitis must be discontinued 
except permitted concomitant therapies (eg, oral antihistamines). Due to the potential to 
affect atopic dermatitis with ultraviolet light exposure, participants must also avoid 
prolonged exposure to the sun and avoid the use of tanning booths, sun lamps or other 
ultraviolet light sources during the study. 
 
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. 
Herbal medications with presumed anti-inflammatory properties or known beneficial effects 
for AD, or that are known to have an effect on drug metabolism (eg St. John’s Wort) must be 
discontinued at least 1 week or 5 half-lives (whichever is longer) before the first dose of 
study intervention. 
 
Participants should refrain from having any vaccinations during the course of study 
participation. 
 
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
Part 2 participants who are WOCBP (see Appendix 4). 
 
6.5.3. Rescue Medicine 
There is no rescue therapy to reverse the AEs observed with PF-07242813; standard medical 
supportive care must be provided to manage the AEs. 
 
Part 2 only: Participants randomized into the study are allowed to take other treatments for 
their disease as prescribed by the investigator, provided they are not included among the 
prohibited concomitant medications (noted in Section 6.5.2.2) and the concomitant drugs and 
doses are maintained unchanged throughout the first 16 weeks of the study. Although no 
specific rescue treatment is recommended, participants randomized into the study may have 
access to standard of care therapy, that may include prohibited treatments and medications 
defined in Section 6.5.2.2, if deemed necessary by the investigator to treat their underlying 
disease. Since there is no information on drug interactions, the general guidance is, if 
possible, to defer initiation of treatment until after the primary AD assessments are complete 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 65 
 
 
at Week 6, to start with topical before systemic treatments, and to use fewer 
immunosuppressing treatments before progressing to more immunosuppressing treatments. 
 
6.6. Dose Modification 
6.6.1. Dose Escalation and Stopping Rules (Part 1) 
Dose escalation stopping rules will be used to determine whether the maximal tolerated dose 
has been attained. Dose escalation may be stopped if it is determined that the limits of safety 
and/or tolerability have been reached. This decision will be made after a discussion takes 
place between the sponsor study team and the investigator. The sponsor study team may not 
overrule the investigator’s decision to stop dose escalation. If dose escalation is stopped 
because of any of these criteria, additional cohorts may receive the same or lower doses of 
the study intervention. 
 
The dose escalation will be terminated based on the following criteria: 
 
• If 50% or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant laboratory, ECG, 
or vital sign abnormalities, in the same organ class, indicating dose-limiting 
intolerance. 
 
• If two-thirds of participants at a given dose level develop an individual participant 
stopping AE (see Section 7.1). 
 
• Dosing will be paused for any SAE that occurs in a participant receiving active 
treatment until causality is fully assessed by the PI and sponsor. Dosing may resume 
if the SAE is determined to be not drug-related by the PI and sponsor. If the SAE is 
determined to be either drug-related or unknown, either dosing will cease or the SAE 
will be evaluated by the sponsor’s protocol review committee (or similar review 
group), which is independent of the study team and investigators. If the protocol 
review committee determines that dosing may resume, a plan that mitigates risks to 
participants with the resumption of dosing will be implemented. Such a plan could 
include a revision of inclusion/exclusion criteria, repeating or reducing the dose, or 
adding appropriate safety monitoring. 
 
• It is determined that the limit of safety and/or tolerability has been reached. This 
decision will be made following discussions between the study team and the 
investigator. 
 
• Other findings that, at the discretion of the study team and investigator, indicate that 
dose escalation should be halted. 
 
• If, at any dose level, the average exposure reaches or exceeds the PK stopping limits, 
Cmax of 1020 µg/mL and AUC168H of 106000 µg.h/mL 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 66 
 
 
• If, based on the observed data, the group mean Cmax or AUC (based on total serum 
concentration) of the next planned dose is projected to exceed the escalation limits, 
that dose will not be explored. Modified doses may be explored if they are not 
expected to exceed PK stopping criteria. 
 
Progression to the next dose will occur if the last dose was well tolerated and after 
satisfactory review of the available safety and PK data. 
 
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 OF STUDY 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for a minimum of 4 half-lives (approximately 70 days) after last dose. 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. 
 
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: 
 
• Any participant who develops Grade 2 or higher adverse events for cardiac and 
blood/bone marrow categories and Grade 3 or higher adverse events in all other 
categories according to criteria defined in CTCAE, v. 5 will be discontinued from 
treatment, and followed until resolution of the adverse event(s). 
 
• If a participant experiences symptoms typical of an allergic reaction, the study drug 
administration should be discontinued immediately and permanently; 
 
• ECG changes (see below); 
• Unacceptable toxicity; 
• Pregnancy. 
ECG Changes 
 
A participant who meets the bulleted criteria based on the average of triplicate ECG readings 
will be withdrawn from the study intervention. 
 
• QTcF >500 msec. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 67 
 
 
• Change from baseline: QTc >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. 
 
7.1.1. Temporary Discontinuation 
If a participant experiences symptoms typical of infusion reactions (eg, lightheadedness, 
nausea, chills, fever), the study intervention infusion should be stopped. At the discretion of 
the investigator, the infusion can be restarted at a slower rate if symptoms are resolved within 
1 hour after the stop of infusion. If symptoms return, then the study intervention 
administration should be discontinued immediately and permanently. 
 
In the event that there is an infusion interruption, the entire duration of drug infusion, from 
the initial start of infusion to the completion of infusion, should not exceed 3 hours. The start 
and stop time of the infusion and the infusion rate and amount of volume infused in the event 
of an interruption will be recorded. Participants will receive appropriate treatment at the 
discretion of the investigator. 
 
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. 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 68 
 
 
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 attend a required study visit: 
 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study; 
 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record; 
 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 69 
 
 
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 (defined as assessments conducted prior to first dose) must be 
completed and reviewed to confirm that potential participants meet all eligibility criteria. The 
investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
 
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the eligibility criteria for the study. If the time between screening 
and dosing exceeds 28 days (up to 1 week) due to delays related to receipt of primary or 
repeat laboratory results, this will not constitute a protocol deviation. 
 
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 the Part 1 SAD cohort is 
approximately 325 mL, for the MAD cohort is approximately 480 mL, and in Part 2 for 
Cohort 9 is approximately 510 mL. The actual collection times of blood sampling may 
change. Additional blood samples may be taken for safety and/or PK assessments at times 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 70 
 
 
specified by Pfizer, provided the total volume taken during the study does not exceed 550 mL 
during any period of 60 consecutive days. 
 
8.1. Assessments of Clinical Effect (Participants with Atopic Dermatitis [Part 2]) 
8.1.1. Fitzpatrick Skin Type Assessment 
As part of baseline characteristics, a skin type assessment will be done at the Screening visit 
using the Fitzpatrick Skin Phototype assessment (Appendix 8: Fitzpatrick Skin Type). This is 
used to classify a person’s skin type by their response to sun exposure (ie, burning or 
tanning). 
 
8.1.2. Eczema Area and Severity Index (EASI) 
The EASI quantifies the severity of a participant’s atopic dermatitis based on both severity of 
lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the 
atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, 
excoriation, and lichenification (each scored separately) for each of four body regions, with 
adjustment for the percent of BSA involved for each body region and for the proportion of 
the body region to the whole body (Hanifin et al. 2001).10 (See Appendix 9: EASI). 
 
 
8.1.4. Columbia Suicide Severity Rating Scale (C-SSRS) 
Columbia suicide severity rating scale is a validated tool to evaluate suicidal ideation and 
behavior (Appendix 15: Columbia Suicide Severity Rating Scale (C-SSRS)) (Posner et al. 
2007).17 
At Screening Visit, if there are “yes” answers on items 4, 5 in the past year or on any 
question in the suicidal behavior section of the C-SSRS in the past 6 months, the participant 
will not be included in the study. 
 
8.1.5. Patient Reported Outcome Measures 
All patient reported outcome measures must be completed by the participant prior to 
significant contact between the participant and site personnel, and before all other activities 
listed above. These include: 
 
8.1.5.1. POEM 
The POEM is a 7-item PRO measure used to assess the impact of AD over the past week 
(Appendix 11: Patient-Oriented Eczema Measure (POEM)). The POEM should be 
completed per the Schedule of Activities (Charman et al. 2004).4 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 71 
 
 
8.1.5.2. Pruritus Numerical Rating Scale (Pruritus NRS) 
The Pruritus NRS (Appendix 12: Pruritus NRS, Severity and Frequency) consists of 
2 assessments: of pruritus severity and of pruritus frequency as detailed below. Pruritus NRS 
will be completed by participants every day for 14 days (either while at home or confined in 
the clinic) after the Day 1 dosing visit and per the Schedule of Activities (Part 2 only). NRS 
assessment for Day 8 visit will be administered at the site. NRS assessments completed prior 
to Day 8 visit should be returned to the clinical site at the Day 8 visit. NRS assessments 
completed at home prior to Day 29 visit should be returned to the clinical site on the nominal 
Day 29 visit (including the Day 2-Day 8 NRS assessments if not previously returned to the 
clinical site) (Phan et al. 2012).16 
8.1.5.2.1. Severity of Pruritus 
The severity of itch (pruritus) due to atopic dermatitis will be assessed using a horizontal 
NRS. Participants will be asked to assess their “itching due to atopic dermatitis over the past 
24 hours” on a NRS anchored by the terms “no itching” (0) and “worst possible itching” 
(10). 
 
8.1.5.2.2. Frequency of Pruritus 
The frequency of itch (pruritus) due to atopic dermatitis will be assessed using a horizontal 
NRS. Participants will be asked to assess “frequency of itching due to atopic dermatitis over 
the past 24 hours” on a NRS anchored by the terms “never/no itching” (0) and 
“always/constant itching” (10). 
 
The pruritus NRS should be completed per the Schedule of Activities (Part 2 only). 
 
8.1.5.3. Patient Global Assessment (PtGA) 
The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time 
on a single item-, 5-point scale (Appendix 13: Patient Global Assessment (PtGA)). The same 
category labels used in the Investigator Global Assessment will be used for the Patient 
Global Assessment, ie, “severe (4)”, “moderate (3)”, “mild (2)”, “almost clear (1)”, and 
“clear (0)”. The PtGA should be completed per the Schedule of Activities. The 5-point scale 
for PGA is: 0, “clear”; 1, “almost clear”; 2, “mild”; 3, “moderate”; 4 “severe”. 
 
8.1.5.4. Dermatology Life Quality Index (DLQI) 
The DLQI (Appendix 17: Dermatology Life Quality Index (DLQI)) is a general dermatology 
questionnaire that consists of 10 items that assess participant health-related quality of life 
(daily activities, personal relationships, symptoms and feelings, leisure, work and school, and 
treatment). It has been extensively used in clinical trials for atopic dermatitis. The DLQI is a 
psychometrically valid and reliable instrument that has been translated into several 
languages, and the DLQI total scores have been shown to be responsive to change. The 
minimally important difference for the DLQI has been estimated as a 2 to 5 point 
improvement from baseline. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 72 
 
 
8.1.5.5. Hospital and Anxiety Depression Scale (HADS) 
The HADS (Appendix 14: Hospital and Anxiety Depression Scale (HADS)) is a 14-item 
PRO measure used to detect states of anxiety and depression over the past week. The HADS 
should be completed as per the Schedule of Activities. 
 
8.1.5.6. Asthma Control Questionnaire, 5 Item Version (ACQ-5) (Asthmatic 
Participants only) 
The 5-question version of the ACQ is a validated questionnaire to evaluate asthma control. 
The 5-item version of the ACQ differs from the full ACQ (7 question version) in that the 
question about short-acting bronchodilator use and FEV1 score are excluded. Participants will 
complete the ACQ questionnaire per the Schedule of Activities A physician, trained 
physician's assistant, nurse practitioner, or study coordinator as acceptable according to local 
regulation will review the assessment for thoroughness. A copy of the ACQ is provided in 
Appendix 19: Asthma Control Questionnaire.12 
8.1.6. Rater Qualifications 
Investigators participating in this study should be experienced in the conduct of inflammatory 
disease clinical trials and have prior training and experience in the required protocol-specific 
AD participant clinical evaluations. The same rater should evaluate the same 
participant(s) whenever possible. 
 
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. Physical Examinations 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. A full physical examination 
will include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated 
physical examination will be focused on general appearance including skin (specific attention 
to infusion and injection site reactions), the respiratory, gastrointestinal, and cardiovascular 
systems, as well as towards participant reported symptoms. 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 73 
 
 
8.2.2. Vital Signs 
Temperature will be measured by oral, tympanic, or temporal artery method, provided the 
same method is used consistently throughout the study. No eating, drinking or smoking is 
allowed for 15 minutes prior to the measurement. 
 
Respiratory rate will be measured after approximately 5 minutes rest in supine position by 
observing and counting the respirations of the participant for 30 seconds and multiplied by 
2. When blood pressure is to be taken at the same time, respiration measurement will be done 
during the 5 minutes of rest and before blood pressure measurement. Post-dose respiratory 
rate measurements to be done at Investigator’s discretion. 
 
Blood pressure and pulse rate will be measured at times specified in the Schedule of 
Activities. Additional collection times, or changes to collection times of blood pressure and 
pulse rate will be permitted, as necessary, to ensure appropriate collection of safety data. 
 
Supine blood pressure will be measured with the participant’s arm supported at the level of 
the heart and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same 
arm (preferably the dominant arm) will be used throughout the study. Blood pressure should 
not be taken from the arm with an intravenous infusion. Participants should be instructed not 
to speak during measurements. If a single measurement is >140 mm systolic and/or >90 mm 
diastolic in healthy participants, or >160 mm systolic and/or >100 mm diastolic in atopic 
dermatitis participants, the blood pressure assessment should be repeated two more times, 
and the average of the three BP values recorded in the CRF and noted in source documents. 
 
The same properly sized and calibrated blood pressure cuff will be used to measure blood 
pressure each time. The use of an automated device for measuring BP and pulse rate is 
acceptable, although, when done manually, pulse rate will be measured in the brachial/radial 
artery for at least 30 seconds. When the timing of these measurements coincides with a blood 
collection, blood pressure and pulse rate should be obtained prior to the nominal time of the 
blood collection. 
 
8.2.3. Electrocardiograms 
12-Lead Standard Electrocardiograms (ECGs) 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 interval, QT interval, QTc intervals and QRS complex. All scheduled 
ECGs should be performed after the participant has rested quietly for at least 10 minutes in a 
supine position. 
 
Triplicate 12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average of 
the triplicate ECG measurements collected before dose administration on Day 1 of each 
cohort will serve as each participant’s baseline QTc value. 
 
When the timing of these measurements coincides with a blood collection, the ECG should 
be obtained prior to the nominal time of the blood collection, blood pressure and pulse rate. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 74 
 
 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements. If the QTc interval for single ECG collections is 
increased by ≥45 msec from the baseline, or an absolute QTc value is ≥500 msec for any 
scheduled ECG, then 2 additional ECGs will be collected, approximately 2-4 minutes apart, 
to confirm the original measurement. If either of the QTc values from these repeated ECGs 
remains above the threshold value (≥45 msec from the baseline; or is ≥500 msec), then a 
single ECG must be repeated at least hourly until QTc values from 2 successive ECGs fall 
below the threshold value that triggered the repeat measurement. 
 
If QTc values remain ≥500 msec (or ≥45 msec from the baseline) for greater than 4 hours (or 
sooner at the discretion of the investigator); or QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring. A cardiologist should be consulted 
if QTc intervals do not return to less than 500 msec (or to <45 msec above the baseline) after 
8 hours of monitoring (or sooner at the discretion of the investigator). 
 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range. 
 
ECG values of potential clinical concern are listed in Appendix 7. 
 
8.2.3.1. Continuous Cardiac Monitoring by Telemetry 
Telemetry will be collected in Part 1 SAD Cohorts (Cohorts 1-8). All abnormal rhythms will 
be recorded and reviewed by the study physician for the presence of rhythms of potential 
clinical concern. The time, duration, and description of the clinically significant event will be 
recorded in the CRF/DCT. In addition, a printed record of the tracing(s) of the clinically 
significant rhythm(s) will be made and retained with other source documents. 
 
Telemetry should be collected using a centralized system that also allows for the storage and 
advanced analysis of all recorded data in order to preserve important events for future 
evaluations. Holter monitoring should not be used in parallel with continuous telemetry, 
unless it is the only means of data storage available at the investigator site, or verifiable 
arrhythmia quantification is required. 
 
To establish a baseline, telemetry should be recorded for at least 2 hours prior to dosing. This 
may be done immediately prior to dosing or at some 2-hour continuous interval in the 
24 hours prior to dosing, as long as the recording is performed when the participant is awake. 
Telemetry may be stopped within a reasonably short period of time prior to dosing, in order 
to avoid interference with study operations conducted immediately before dosing. However, 
it is expected that the telemetry leads will be in place and the system connected prior to 
dosing. Post-dose telemetry will continue for 8 hours after dosing. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 75 
 
 
8.2.4. 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. 
 
8.2.5. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL and the results be available prior to the administration of investigational 
treatment. 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). 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. 
 
In the case of a positive confirmed pregnancy, the participant will be withdrawn from 
administration of study intervention but may remain in the study for observation. 
 
8.2.6. Infusion and Injection Site Reaction Assessment 
Participants will be monitored for signs of any infusion or injections site reactions, including 
but not limited to erythema, swelling, bruising, pain or pruritus at times specified in the SoA. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 76 
 
 
Any signs or symptoms related to either an infusion or injection site reaction should be 
treated according to the Investigator’s standard of care and reported as adverse events. All 
anaphylactic reactions will be assessed according to Sampson’s criteria. 
 
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 the 
final scheduled visit (or at least 4 half-lives of PF-07242813, whichever is longer), after the 
last administration of the study intervention. 
 
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment. 
 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
 
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 77 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 78 
 
 
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 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 female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy. 
 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact. 
 
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). 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 79 
 
 
• If EDP occurs in a participant, 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 last dose, or 5 terminal half-lives 
after the last dose, whichever is longer. 
 
• 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, the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 
 
• Spontaneous abortion including miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 80 
 
 
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. 
 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 81 
 
 
8.3.8. Adverse Events of Special Interest 
Not applicable. 
 
8.3.8.1. Lack of Efficacy 
Not applicable in Part 1. For Part 2 participants that do not gain clinical benefit following 
study intervention administration, lack efficacy should be captured as an AE. 
 
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 within 24 hours. 
 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF. 
 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 82 
 
 
8.4. Treatment of Overdose 
For this study, any dose of PF-07242813 greater than 1000 mg within a 24-hour time period 
will be considered an overdose. 
 
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 5 half-lives or 28 calendar days after the overdose of PF-07242813 (whichever 
is longer). Closely monitor the participant for any AEs/SAEs. 
 
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. 
 
5. Obtain a blood sample for PK analysis within 28 days from the date of the last dose 
of study intervention if requested by the medical monitor (determined on a 
case-by-case basis). 
 
8.5. Pharmacokinetics 
Blood samples of approximately 4 mL will be collected for measurement of serum 
concentrations of PF-07242813 as specified in the SoA. Instructions for the collection and 
handling of biological samples will be provided in the laboratory manual or by the sponsor. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
 
The actual times for PK assessment may change, and if needed, additional PK samples may 
be taken at times specified by Pfizer, provided the total serum volume taken during the study 
does not exceed 550 mL during any period of 60 consecutive days. All efforts will be made 
to obtain the samples at the exact nominal time relative to dosing. Collection of samples up 
to and including 10 hours after dose administration that are obtained within 10% of the 
nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will not be 
captured as a protocol deviation, as long as the exact time of the collection is noted on the 
source document and the CRF/DCT. Collection of samples more than 10 hours after dose 
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF/DCT. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 83 
 
 
 
 
 
Genetic analyses will not be performed on these blood samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained. 
 
Samples collected for measurement of serum concentrations of PF-07242813 will be 
analyzed using a validated analytical method in compliance with applicable SOPs. 
 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. 
 
Drug concentration information that may unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded. 
 
8.6. Pharmacodynamics 
 
8.6.1. Skin Biopsies 
 
 
Briefly, index lesion sites may be located on the torso (upper and 
mid back, chest), abdomen, buttocks, upper arms, and upper legs. Index lesions may not be 
located on the scalp, face, elbows, knees, lower legs, genital area and inguinal area, 
intertriginous areas and lower back. Punch biopsies of the lesional and nonlesional- skin will 
be obtained at the time points specified in the Schedule of Activities, processed, and shipped 
according to the instructions to be provided in a separate study manual. Skin biopsies will be 
sent to designated laboratories for analysis following a schedule to be determined. The 
shipment address and laboratory contact information will be provided to the investigator. 
 
As skin biopsies may be associated with risk of bleeding or infection, participants will be 
instructed to contact the investigator or other designated site staff if they experience bleeding, 
warmth, swelling, tenderness, or erythema at the biopsy site; an unscheduled visit may be 
required for clinical assessment. 
CCI 
CCI 
CCI 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 84 
 
 
8.7. Genetics 
8.7.1. Specified Genetics 
Genetics (specified analyses) are not evaluated in this study. 
 
8.7.2. Banked Biospecimens for Genetics 
A 4-mL blood sample optimized for DNA isolation Prep D1 will be collected as local 
regulations and IRBs/ECs allow. 
 
Banked Biospecimens may be used for research related to the study intervention(s) and 
atopic dermatitis or other inflammatory skin condition. Genes and other analytes 
(eg, proteins, RNA, nondrug metabolites) may be studied using the banked samples. 
 
See Appendix 5: Genetics for information regarding genetic research. Details on processes 
for collection and shipment of these samples can be found in the laboratory manual. 
 
8.8. Biomarkers 
Collection of samples for biomarker research is also part of this study. 
 
The following samples for biomarker research are required and will be collected from all 
participants in this study as specified in the SoA: 
 
• Serum to monitor select anterior pituitary hormones and hormones under anterior 
pituitary regulatory control (Parts 1 & 2); 
 
• Plasma to monitor for potential cytokine release (Parts 1 & 2); 
• Serum or plasma for total IgE, TARC/CCL17, IL-31, IL-17A (Part 2 only); 
• Whole blood for potential assessment of lymphocyte subsets (Part 2 only); 
• Non-lesional and lesional skin biopsies for histology and RNA (Part 2 only). 
8.8.1. Specified Gene Expression (RNA) Research 
8.8.1.1. Skin Biopsies for RNA Analysis 
Four (4) mm punch biopsies will be collected from non-lesional and lesional skin according 
to the times outlined in the Schedule of Activities. The samples will be processed and 
preserved in buffers appropriate for bulk and single cell RNA Sequencing. CCI  
 
Details on processes for collection and shipment of these samples can be found in the 
laboratory manual. 
 
Samples may be stored at a facility selected by the sponsor for a maximum of 10 years (or 
according to local regulations) following the last participant’s last visit for the study. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 85 
 
 
8.8.2. Specified Cellular Research 
8.8.2.1. Skin Biopsies for Histopathology and Immuno-histopathology 
Four (4) mm punch biopsies will be collected from non-lesional and lesional skin according 
to the times outlined in the Schedule of Activities. The samples will be preserved in formalin 
and embedded in paraffin. Tissue sections will be stained andCCI 
 
research into changes in tissue pathology and infiltrating cell types. 
 
Samples may be stored at a facility selected by the sponsor for a maximum of 10 years (or 
according to local regulations) following the last participant’s last visit for the study. 
 
8.8.2.2. Lymphocyte Subsets 
A 10-mL blood sample for measurement of lymphocyte subsets by flow cytometry will be 
collected according to the times outlined in the Schedule of Activities. CCI 
 
Lymphocyte subsets may include T cells, B cells, NK 
cells, T cell subsets (Th1, Th2, Th17) and CD1a-restricted T cells. 
 
Details on processes for collection and shipment of these samples can be found in the 
laboratory manual. 
 
Samples may be stored at a facility selected by the sponsor for a maximum of 10 years (or 
according to local regulations) following the last participant’s last visit for the study. 
 
8.8.3. Specified Protein Research 
CCI 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
PFIZER CONFIDENTIAL 
Page 86 
 
 
 
 
 
8.8.3.5. Anterior Pituitary Hormones and Hormones under Anterior Pituitary 
Regulatory Control 
 
 
 
 
 
 
 
 
Banked Biospecimens will be collected as local regulations and IRB/ECs allow. 
 
Banked Biospecimens may be used for research related to the study intervention(s) and 
atopic dermatitis or other inflammatory skin conditions. Genes and other analytes 
(eg, proteins, RNA, nondrug metabolites) may be studied using the banked samples. 
 
See Appendix 5: Genetics for information regarding genetic research. Details on processes 
for collection and shipment of these samples can be found in the lab manual. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
PFIZER CONFIDENTIAL 
Page 87 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
9.1. Estimands and Statistical Hypotheses 
The primary estimand (for secondary endpoint EASI) will be the population average 
treatment effect on percent change from baseline in EASI score relative to placebo at Week 6 
in the absence of prohibited medication. All observations after the initiation of prohibited 
medication will be set to missing. Missing data from all causes, including post-prohibited 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 88 
 
 
medication use will be imputed in the PF-07242813 dose arms using a jump to control 
method using the distribution of the placebo group. 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 percent change from baseline in each treatment 
arm compared to the corresponding vehicle. 
The secondary estimand CCI 
 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 time points specified in Schedule of Activities. 
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 placebo. EASI-50, EASI-75, EASI-90 and other EASI scores 
will be treated in a similar manner. 
 
9.2. Sample Size Determination 
9.2.1. Healthy Participant Single Ascending and Multiple Dose (Part 1) 
A sample size of approximately 52 healthy participants in 8 SAD cohorts (36 randomized to 
single PF-07242813 dose and 16 randomized to placebo) and up to 40 healthy participants in 
5 MAD cohorts (30 randomized to multiple doses of PF-07242813 and 10 randomized to 
placebo) is not based on statistical considerations. The sample size was based on the clinical 
consideration to provide safety and tolerability information and on the need to minimize 
exposure to healthy participants at each dose level. In addition, 1 cohort of approximately 
5 healthy Japanese participants (4 PF-07242813: 1 placebo) will be included and this sample 
size has been judged sufficient to obtain preliminary evaluation of safety, tolerability and PK 
data in this population. No formal inferential statistics will be applied to the safety, 
pharmacodynamic or pharmacokinetic data. 
 
Participants who discontinue prior to completion of the study for other than safety reasons 
may be replaced, at the discretion of the investigator and sponsor. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 89 
 
 
9.2.2. Atopic Dermatitis Cohorts (Part 2) 
The sample size calculation is based on the secondary endpoint (percent change from 
baseline in EASI score at Week 6). A total of 24 randomized participants with a 
randomization ratio of 2:1 into the treatment and placebo group will provide approximately 
80% power to detect a difference of 50 in percent change from baseline with a common 
standard deviation 46% between PF-07242813 and the placebo arm with 1-sided alpha=0.05. 
 
Cohort 9 will enroll 24 adult participants with moderate to severe AD. 
 
9.3. Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
 
Population 
Description 
Safety Analysis Set 
All participants randomly assigned to study intervention and 
who receive at least 1 dose of study intervention. Participants 
will be analyzed according to the product they actually 
received. 
 
 
Defined Population for 
Analysis 
Description 
Modified Intention to 
Treat (mITT) 
All participants randomly assigned to study intervention and 
who apply at least 1 dose of study intervention. 
PK concentration set 
All enrolled participants who applied at least one dose of 
PF-07242813 and in whom at least once concentration value 
is reported. 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 90 
 
 
9.4.1. Efficacy Analyses (Part 2 Only) 
Endpoint 
Statistical Analysis Methods 
Secondary 
(percent 
change from 
baseline) 
 
 
 
 
 
 
CCI 
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. 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’s as implemented in SAS 
PROC MIANALYZE. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 91 
 
 
9.4.2. Safety Analyses 
 
Endpoint 
Statistical Analysis Methods 
Primary 
The safety data will be summarized in accordance with Pfizer Data 
Standards. All participants who receive study intervention (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); 
• ECG and cardiac telemetry changes from baseline; 
• 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. 
CCI 
 
 
9.4.2.1. 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 92 
 
 
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. 
 
If more than 1 ECG is collected at a nominal time after dose administration (for example, 
triplicate ECGs), the mean of the replicate measurements will be used to represent a single 
observation at that time point. If any of the 3 individual ECG tracings has a QTc value 
>500 msec, but the mean of the triplicates is not >500 msec, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500-msec value in appropriate clinical context. However, values from individual tracings 
within triplicate measurements that are >500 msec will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 msec. Changes 
from baseline will be defined as the change between the postdose QTc value and the average 
of the time-matched baseline triplicate values on Day -1, or the average of the predose 
triplicate values on Day 1. 
 
9.4.3. Pharmacokinetics Analyses 
9.4.3.1. Analysis Population 
The PK concentration population is defined as all randomized participants who received a 
dose of PF-07242813 and in whom at least 1 serum concentration value is reported. The PK 
parameter analysis population is defined as all randomized participants who received a dose 
of PF-07242813 and who have at least 1 of the PK parameters of interest calculated. 
 
9.4.3.2. Derivation of Pharmacokinetic Parameters 
9.4.3.2.1. Pharmacokinetic Parameters for Part 1 
The PK parameters to be assessed, their definition, and method of determination are listed in 
Table 6. Actual PK sampling times will be used in the derivation of PK parameters. 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 93 
 
 
Table 6. 
Serum PK Parameters for Part 1 
 
Parameter 
Definition 
Method of Determination 
Single Dose 
AUClast 
Concentration-time profile from time zero to 
the time of the last 
quantifiable concentration (Clast) 
Linear/Log trapezoidal method 
AUClast(dn) 
Dose normalized AUClast 
AUClast/Dose 
AUCinfa 
Area under the serum concentration 
time- profile from time zero extrapolated to 
infinite time 
AUClast + (Clast*/kel), 
where Clast* is the predicted serum 
concentration at the last quantifiable time 
point estimated from the log-linear regression 
analysis 
CCI 
Cmax 
Maximum serum concentration 
Observed directly from data 
Cmax(dn) 
Dose normalized Cmax 
Cmax/Dose 
Tmax 
Time for Cmax 
Observed directly from data as time of first 
occurrence 
t1/2a 
Terminal elimination half-life 
Loge(2)/kel, 
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
loglinear -concentration time- curve. Only 
those data points judged to describe the 
terminal log-linear decline will be used in the 
regression 
CCI 
Multiple Doses 
AUCτ 
Area under the serum 
concentration time- profile over the dosing 
interval τ where τ=2 weeks/336 hours 
Linear/Log trapezoidal method 
CCI 
Cmax 
Maximum serum concentration 
Observed directly from data 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 94 
 
 
 
Parameter 
Definition 
Method of Determination 
t1/2a 
Terminal elimination half-life 
Loge(2)/kel, 
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
loglinear -concentration time- curve. Only 
those data points judged to describe the 
terminal log-linear decline will be used in the 
regression 
CL/F and CLa Apparent clearance for SC dosing (CL/F) and 
Systemic clearance (CL) for IV dosing 
Dose/AUCt, if steady state is achieved 
Vz/Fa 
Apparent volume of distribution following SC 
dosing 
Dose/AUCinf*kel 
F 
Apparent bioavailability of SC injection 
AUCt (SC, sd)/AUC14 days (IV, sd) 
a If data permit. 
 
9.4.3.3. Statistical Methods for PK Data 
No formal inferential statistics will be applied to the pharmacokinetic data. 
 
9.4.3.3.1. PK Data in Part 1 
The serum concentration of PF-07242813 will be listed and descriptively summarized by 
nominal PK sampling time and treatment group. Individual subject and median profiles of the 
serum concentration-time data will be plotted by treatment group using actual (for individual) 
and nominal (for median) times respectively. Median profiles will be presented on both linear 
and log scales. 
 
The PK parameters in Table 6 will be summarized descriptively by treatment group in 
healthy and AD participants in accordance with Pfizer data standards. Summary statistics 
will also include the geometric mean and coefficient of variation for all parameters except 
Tmax. 
 
Where data permit, dose normalized (to a 1 mg dose) Cmax, AUCinf, AUClast and/or AUCτ, 
will be plotted against dose and administration route, as appropriate for single dose and 
multiple doses (using a logarithmic scale). The plot will include individual subject values and 
the geometric means for each dose. These plots will be used to help understand the 
relationship between the PK parameters and dose and/or administration route. 
 
The PK data from Japanese participants will be summarized separately. 
 
9.4.3.3.2. PK data in Part 2 
The serum concentration of PF-07242813 for Part 2 will be listed and summarized with 
descriptive statistics by nominal time and visit for each cohort. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 95 
 
 
A population PK modeling may be performed by combining Part 1 and Part 2 PK data to 
estimate specific PK parameters and/or exposures in individual participants in Part 2. In 
addition, a relationship between exposures and clinical efficacy/safety endpoints may be 
evaluated using population PK/PD approach. Any population analyses conducted will not be 
part of the CSR and may be reported separately. 
CCI 
 
 
 
 
9.4.5. Other Analyses 
 
 
Patient recorded outcomes (PROs) will be listed and reported in tabular and graphical 
displays as required. The handling of item non-response and other missing data issues will be 
handled on a case by case basis as specified by the authors of the instruments in order to 
preserve the validity of the instruments. 
 
9.5. Interim Analysis 
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessments, facilitating dose-escalation decisions, PK/PD modeling, 
and/or supporting clinical development. 
 
9.6. Data Monitoring Committee or Other Independent Oversight Committee 
This study will not use a Data Monitoring Committee (DMC). 
CCI 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 96 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 97 
 
 
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 participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data. 
 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICD. 
 
Participants must be 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 98 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 99 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 100 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 101 
 
 
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 clinical monitoring plan. 
 
Description of the use of computerized system is documented in eCRF Completion 
Guidelines. 
 
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; 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 102 
 
 
• 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 103 
 
 
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 Binder. 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 104 
 
 
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 7. 
Protocol-Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
MCV 
MCH 
MCHC 
Platelet count 
WBC count 
Total neutrophils 
(Abs) 
Eosinophils (Abs) 
Monocytes (Abs) 
Basophils (Abs) 
Lymphocytes (Abs) 
BUN and creatinine 
Glucose (fasting) 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (bicarbonate) 
AST, ALT 
Total bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
pH 
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte esterase 
Urobilinogen 
Urine bilirubin 
Microscopya 
At screening only: 
• FSHb 
• Hepatitis B surface 
antigend 
• Hepatitis C antibodye 
Screening and as indicated 
• Pregnancy test (β-hCG)c 
• Urine drug screeningf 
a. 
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase. 
b. Serum; For confirmation of postmenopausal status only. 
c. 
Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IRB/EC. Serum or urine β-hCG for female participants of childbearing potential 
provided results are available prior to dosing at the randomization and each study visit thereafter. 
d. HBsAb test if screening results for HBsAg are negative and HBcAb are positive. 
e. 
HCV RNA test will be done as a reflex for positive HCVAb test. 
f. 
Urine drug testing requirements: amphetamines, benzodiazepines, cocaine, methadone, opiates, 
 
propoxyphene, THC. 
 
 
Investigators must document their review of each laboratory safety report. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 105 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 106 
 
 
 
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 
should be considered serious. 
Hospitalization for elective treatment of a preexisting condition that did not worsen from 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 107 
 
 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 108 
 
 
 
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. 
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 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 109 
 
 
 
• 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. 
AEs in the cardiac and blood/bone categories will be evaluated applying Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5. For reporting purposes, 
CTCAE severity grades are to be interpreted as follows: 
• Grade 1 events correlate to Mild. 
• Grade 2 events correlate to Moderate. 
• Grade 3 and higher events correlate to 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 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 110 
 
 
 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send 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. 
• If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology. 
• New or updated information will be recorded in the originally completed CRF. 
• The investigator will submit any updated SAE data to the sponsor within 24 hours 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 111 
 
 
 
of receipt of the information. 
10.3.4. Reporting of SAEs 
 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 112 
 
 
10.4. Appendix 4: Contraceptive Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria 
No contraception methods are required for male participants in this study, as the calculated 
safety margin is ≥100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies. 
 
10.4.2. Female Participant Reproductive Inclusion Criteria 
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies: 
 
• Is not a WOCBP (see definitions below in Section 10.4.3). 
OR 
• For Part 1: Is a WOCBP and using a contraceptive method that is highly effective 
(with a failure rate of <1% per year), with low user dependency and not hormonally 
based, as described below during the intervention period and for at least 60 days 
(7 x terminal half-life) after the last dose of study intervention, which corresponds to 
the time needed to eliminate any reproductive safety risk of the study intervention(s). 
The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention. 
 
• For Part 2: Is a WOCBP and using a contraceptive method that is highly effective 
(with a failure rate of <1% per year), with low user dependency (including 
hormonally based methods), or, is using contraceptive method that is highly effective 
(with a failure rate of <1% per year) that is not of low user dependency (including 
hormonally based methods) together with a barrier method as described below during 
the intervention period and for at least 60 days (7 x terminal half-life) after the last 
dose of study intervention, which corresponds to the time needed to eliminate any 
reproductive safety risk of the study intervention(s). 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 113 
 
 
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 non-estrogen containing 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. 
 
Highly Effective Methods That Have Low User Dependency 
 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation. (Prohibited for Part 1 healthy participants. Permitted only for Part 2 AD 
participants.) 
 
2. Intrauterine device. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 114 
 
 
3. Intrauterine hormone-releasing system. (Prohibited for Part 1 healthy participants. 
Permitted only for Part 2 AD participants.) 
 
4. Bilateral tubal occlusion. 
 
5. Vasectomized partner. 
 
• Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days. 
 
Highly Effective Methods That Are User Dependent 
 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: 
 
• Oral; 
• Intravaginal; 
• Transdermal. 
7. Progestogen-only hormone contraception associated with inhibition of ovulation: 
 
• Oral; 
• Injectable. 
8. Sexual abstinence: 
 
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant. 
 
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent: 
 
• Male or female condom with or without spermicide; 
• Cervical cap, diaphragm, or sponge with spermicide; 
• A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods). 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 115 
 
 
10.5. Appendix 5: Genetics 
Use/Analysis of DNA 
• Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis. 
 
• The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation. 
 
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to PF-07242813 or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves. 
 
• The results of genetic analyses may be reported in CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report. 
 
• The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
 
• The samples will be retained as indicated: 
• Samples for banking will be stored indefinitely or for another period as per local 
requirements. 
 
• Participants may withdraw their consent for the storage and/or use of their Banked 
Biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed. Data already generated from the samples will 
be retained to protect the integrity of existing analyses. 
 
• Banked Biospecimens will be labeled with a code. The key between the code and the 
participant’s personally identifying information (eg, name, address) will be held at the 
study site and will not be provided to the sample bank. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 116 
 
 
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up 
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). 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 117 
 
 
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 co-formulated 
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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 118 
 
 
10.7. Appendix 7: ECG Findings of Potential Clinical Concern 
 
ECG Findings That May Qualify as AEs 
• Marked sinus bradycardia (rate <40 bpm) lasting minutes. 
• New PR interval prolongation >280 msec. 
• New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline. 
• New-onset atrial flutter or fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm. 
• New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration. 
• Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive ventricular 
complexes. 
ECG Findings That May Qualify as SAEs 
• QTcF prolongation >500 msec. 
• New ST-T changes suggestive of myocardial ischemia. 
• New-onset left bundle branch block (QRS >120 msec). 
• New-onset right bundle branch block (QRS >120 msec). 
• Symptomatic bradycardia. 
• Asystole: 
• In awake, symptom-free 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 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 119 
 
 
 
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 SAEs 
• 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. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 120 
 
 
10.8. Appendix 8: Fitzpatrick Skin Type 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 121 
 
 
10.9. Appendix 9: EASI 
The EASI quantifies the severity of a participant’s atopic dermatitis based on both severity of 
lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the 
atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, 
excoriation, and lichenification (each scored separately) for each of four body regions, with 
adjustment for the percent of BSA involved for each body region and for the proportion of 
the body region to the whole body. 
 
Lesion Severity by Clinical Signs: The basic characteristics of atopic dermatitis lesions 
erythema, induration/papulation, excoriation, and lichenification- provide a means for 
assessing the severity of lesions. Assessment of these four main clinical signs is performed 
separately for four body regions: head and neck, upper limbs, trunk (including axillae and 
groin) and lower limbs (including buttocks). Average erythema, induration/papulation, 
excoriation, and lichenification- are scored for each body region according to a 4 point scale: 
0 = absent; 1 = mild; 2 = moderate; 3 = severe. Morphologic descriptors for each clinical sign 
severity score are shown in Table 8. 
 
Table 8. 
Clinical Sign Severity Scoring Criteria for the Eczema Area and Severity 
Index (EASI) 
 
Score 
Description* 
Erythema (E) 
0 
Absent 
None; may have residual discoloration (post-inflammatory 
hyperpigmentation and/or hypopigmentation) 
1 
Mild 
Light pink to light red 
2 
Moderate 
Red 
3 
Severe 
Deep, dark red 
Induration/Papulation (I) 
0 
Absent 
None 
1 
Mild 
Barely palpable to slight, but definite hard thickened skin and/or 
papules 
2 
Moderate 
Easily palpable moderate hard thickened skin and/or papules 
3 
Severe 
Severe hard thickened skin and/or papules 
Excoriation (Ex) 
0 
Absent 
None 
1 
Mild 
Slight, but definite linear or picked scratch marks or penetrating 
surface injury 
2 
Moderate 
Moderate linear or picked scratch marks or penetrating surface 
injury 
3 
Severe 
Severe linear or picked scratch marks or penetrating surface 
injury 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 122 
 
 
 
  
* The EASI will exclude scalp, palms, and soles from the assessment/scoring. 
 
Percent BSA with Atopic Dermatitis: The number of handprints of skin afflicted with 
atopic dermatitis in a body region can be used to determine the extent (%) to which a body 
region is involved with atopic dermatitis (Table 9). When measuring, the handprint unit 
refers to the size of each individual participant’s hand with fingers in a closed position. 
 
Table 9. 
Handprint Determination of Body Region Surface Area (BSA) 
 
Body Region 
Total Number of 
Handprints in Body 
Region* 
Surface Area of Body 
Region Equivalent of One 
Handprint* 
Head and Neck 
10 
10% 
Upper Limbs 
20 
5% 
Trunk (including axillae and 
groin/genitals) 
30 
3.33% 
Lower Limbs (including 
buttocks) 
40 
2.5% 
Handprint refers to the hand size of each individual participant. 
* The number of handprints will be for the entire body region; these values will not be adjusted for exclusion 
of scalp, palms, and soles from the BSA assessment. 
 
The extent (%) to which each of the four body regions is involved with atopic dermatitis is 
categorized to a numerical Area Score using a non-linear scaling method according to the 
following BSA scoring criteria (Table 10). 
 
Table 10. Eczema Area and Severity Index (EASI) Area Score Criteria 
 
Percent BSA with Atopic Dermatitis in a Body Region 
Area Score 
0% 
0 
>0 - <10% 
1 
10 - <30% 
2 
30 - <50% 
3 
50 - <70% 
4 
70 - <90% 
5 
90 - 100% 
6 
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 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 123 
 
 
Body Region Weighting: Each body region is weighted according to its approximate 
percentage of the whole body (Table 11 Table 9). 
 
Table 11. Eczema Area and Severity Index (EASI) Body Region Weighting 
 
Body Region 
Body Region Weighting 
Head and Neck 
0.1 
Upper Limbs 
0.2 
Trunk (including axillae and 
groin/genitals) 
0.3 
Lower Limbs (including buttocks) 
0.4 
* 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 3. 
 
Equation 3: EASI = 
0.1Ah(Eh+Ih+Exh+Lh) + 0.2Au(Eu+Iu+ExU+Lu) + 
0.3At(Et+It+Ext+Lt) + 0.4Al(El+Il+Exl+Ll) 
A = Area Score; E = erythema; I = induration/papulation; Ex = excoriation; 
L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs 
 
The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores 
representing greater severity of atopic dermatitis. The EASI should be completed per the 
Schedule of Activities. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 124 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 125 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 126 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 127 
 
 
 
 
Overall, how would you describe your Atopic Dermatitis right now? 
Choose only ONE response. 
Severe 
Moderate 
Mild 
Almost Clear 
 
Clear 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 129 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 130 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 131 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 132 
 
 
 
 
 
 
 
Major Criteria (must have at least three) 
Pruritus 
Typical morphology and distribution: 
Adults: flexural lichenification or linearity 
Children and infants: involvement of facial and extensor surfaces 
Chronic or relapsing dermatitis 
Personal or family history of atopy 
Minor Criteria (must have at least three) 
Xerosis 
Icthyosis/keratosis pilaris/palmer hyperlinearity 
Immediate (type 1) skin test reactivity 
Elevated serum IgE 
Early age at onset 
Tendency to skin infections (Staphylococcus aureus, herpes simplex)/impaired cellular 
immunity 
Hand/foot dermatitis 
Nipple eczema 
Cheilitis 
Conjunctivitis 
Dennie-Morgan fold 
Keratoconus 
Anterior subcapsular cataracts 
Orbital darkening 
Facial pallor/erythema 
Pityriasis alba 
Anterior neck folds 
Itch when sweating 
Intolerance to wool and lipid solvents 
Perifollicular accentuation 
Food intolerance 
Course influenced by environmental/emotional factors 
White dermographism/delayed blanch 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 133 
 
 
 
 
 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 134 
 
 
 
 
 
 
 
 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or 
both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula): 
 
AND AT LEAST ONE OF THE FOLLOWING 
 
a. 
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia). 
 
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], 
syncope, incontinence). 
 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient 
(minutes to several hours): 
 
c. 
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula). 
 
d. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia). 
 
e. 
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence). 
 
f. 
Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting). 
 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
 
g. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic 
BP*. 
 
h. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s 
baseline. 
 
PEF, Peak expiratory flow; BP, blood pressure. 
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less 
than (70 mm Hg + [2 X age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
CCI 
 
PFIZER CONFIDENTIAL 
Page 135 
 
 
 
 
Please answer Questions 1-5 
 
Circle the number of the response that best describes how you have been during the past 
week. 
 
1. On average, during the past week, how often were you woken by your asthma during the 
night? 
 
0 Never 
 
1 Hardly ever 
 
2 A few times 
 
3 Several times 
 
4 Many times 
 
5 A great many times 
 
6 Unable to sleep because of asthma 
 
2. On average, during the past week, how bad were your asthma symptoms when you woke 
up in the morning? 
 
0 No symptoms 
 
1 Very mild symptoms 
 
2 Mild symptoms 
 
3 Moderate symptoms 
 
4 Quite severe symptoms 
 
5 Severe symptoms 
 
6 Very severe symptoms 
 
3. In general, during the past week, how limited were you in your activities because of your 
asthma? 
 
0 Not limited at all 
 
1 Very slightly limited 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 136 
 
 
2 Slightly limited 
 
3 Moderately limited 
 
4 Very limited 
 
5 Extremely limited 
 
6 Totally limited 
 
4. In general, during the past week, how much shortness of breath did you experience 
because of your asthma? 
 
0 None 
 
1 A very little 
 
2 A little 
 
3 A moderate amount 
 
4 Quite a lot 
 
5 A great deal 
 
6 A very great deal 
 
5. In general, during the past week, how much of the time did you wheeze? 
 
0 Not at all 
 
1 Hardly any of the time 
 
2 A little of the time 
 
3 A moderate amount of the time 
 
4 A lot of the time 
 
5 Most of the time 
 
6 All the time 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 137 
 
 
10.20. Appendix 20: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
β-HCG 
Beta-human chorionic gonadotropin 
Abs 
absolute 
ACQ-5 
5-item version of the asthma control questionnaire 
AD 
atopic dermatitis 
CCI 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
ATS/ERS 
American Thoracic Society/European Respiratory Society 
AUC 
area under the curve 
AUC24 
area under the concentration-time curve from time 0 to 24 hours 
AUC504 
area under the concentration-time curve from time 0 to 504 hours 
AUCinf 
area under the concentration-time profile from time zero to infinity 
AUClast 
area under the concentration-time profile from time zero to the time of 
the last quantifiable concentration 
AUCtau 
area under the concentration–time curve within dosing interval 
AV 
atrioventricular 
BMI 
body mass index 
BP 
blood pressure 
BPM 
beats per minute 
BSA 
body region surface area 
BUN 
blood urea nitrogen 
CaPS 
Clinical analysis of Pfizer Standards 
Cav 
average concentration over dosing interval 
CCL17 
chemokine (C-C motif) ligand 17 
CDISC 
Clinical data interchange standards consortium 
CDRs 
complementarity-determining regions 
CHO 
Chinese hamster ovary 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CCI 
Cmax 
maximum observed concentration 
CO2 
carbon dioxide (bicarbonate) 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID 
coronavirus 
CPT 
current procedural terminology 
CRA 
Clinical Research Associate 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 138 
 
 
 
Abbreviation 
Term 
CRF 
case report form 
CRO 
clinical research organization 
CRS 
chronic rhinosinusitis 
CRSwNP 
chronic rhinosinusitis with nasal polyps 
CRU 
clinical research unit 
CsA 
cyclosporine A 
CSR 
clinical study report 
C I 
CT 
clinical trial 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
cardiovascular 
DCT 
data collection tool 
DILI 
drug induced liver injury 
CCI 
dn 
dose normalized 
DNA 
deoxyribonucleic acid 
EASI 
eczema area and severity index 
EBV 
Epstein-Barr virus 
EC 
ethics committee 
ECG 
electrocardiogram 
EDP 
exposure during pregnancy 
EDTA 
Edetic acid (ethylenediaminetetraacetic acid) 
EMA 
European Medicines Agency 
EOS 
end of study 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
I 
FCV 
forced vital capacity 
FDA 
Food and Drug Administration (United States) 
FEV1 
forced expiratory volume in one second 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transpeptidase 
GLP 
good laboratory practice 
HADS 
Hospital and Anxiety Depression Scale 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HCV Ab 
Hepatitis C antibody 
HDM 
house dust mite 
HED 
Human equivalent dose 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 139 
 
 
 
Abbreviation 
Term 
CCI 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
HV 
healthy volunteer 
IB 
Investigator’s Brochure 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ID 
identification 
CCI 
CCI 
IgE 
immunoglobulin E 
CCI  
IgG1 
Immunoglobulin Gamma 1 
CCI 
IL1RL1 
Interleukin 1 Receptor-Like 1 
ILCs 
innate lymphoid cells 
IMP 
investigational medicinal product 
IND 
investigational new drug 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
institutional review board 
ISR 
injection site-reactions 
IUD 
intrauterine device 
IV 
intravenous 
JAK 
Janus Kinase 
K2EDTA 
Potassium salt ethylenediaminetetraacetic acid 
LBBB 
left bundle branch block 
LFT 
liver function test 
mAb 
monoclonal antibody 
MABEL 
minimum anticipated biological effect level 
MAD 
multiple ascending dose 
MAR 
missing at random 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MD 
multiple dose 
MedDRA 
medical dictionary for regulatory activities 
MHC 
major histocompatibility process 
mm2 
IL-33 amino acids 112-270 with 4 cysteines changed to serine 
mRNA 
messenger ribonucleic acid 
MRT 
mean residence time 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 140 
 
 
Abbreviation 
CCI 
MTX 
n or N 
N/A 
NAb 
NB-UVB 
ND 
NHANES III 
NK 
NKT 
NOAEL 
NPS 
NRS 
NSAIDs 
PACL 
PBMC 
Pbo 
PD 
PDE 
PE 
PF 
PI 
PK 
pM 
CCI  
PR 
CCI 
CCI 
PT 
CCI 
CCI  
Q2W 
Q4W 
QTc 
QTcF 
Rac 
RBC 
RNA 
RR 
SAD 
SAE 
SAP 
Term 
 
methotrexate 
number 
not applicable 
neutralizing antibody 
Narrow Band Ultraviolet B 
not determined 
Third National Health and Nutrition Examination Survey 
natural killer cells 
natural killer T-lymphocytes 
no observed adverse effect level 
Nasal polyp score 
numerical rating scale 
nonsteroidal anti-inflammatory drugs 
Protocol Administrative Change Letter 
peripheral blood mononuclear cell 
placebo 
pharmacodynamics 
phosphodiesterase 
physical examination 
PF-06817024 
principal investigator 
pharmacokinetics 
Picomolar 
 
pulse rate 
 
 
prothrombin time 
 
 
every 2 weeks 
every 4 weeks 
corrected QT 
Federicia’s corrected QT 
accumulation ratio 
red blood cell 
ribonucleic acid 
respiratory rate 
single ascending dose 
serious adverse event 
statistical analysis plan 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 141 
 
 
 
Abbreviation 
Term 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous 
SCORAD 
scoring atopic dermatitis 
SCr 
serum creatinine 
SD 
single dose 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
CCI 
SoA 
Schedule of Activities 
SOC 
System Organ Classes 
SOP 
Standard Operating Procedure 
SPR 
Surface plasmon resonance 
SRSD 
Single reference safety document 
t½ 
terminal half-life 
T4 
thyroxine test 
TARC 
thymus and activation regulated chemokine 
TB 
tuberculosis 
Tbili 
total bilirubin 
TCR 
T-cell receptor 
TEAEs 
treatment emergent adverse events 
Th2 
T lymphocytes 
THC 
tetrahydrocannabinol 
TK 
toxicokinetics 
Tmax 
time to reach maximum concentration 
TMDD 
Target-mediated drug disposition 
CCI 
ULN 
upper limit of normal 
UPSIT 
University of Pennsylvania smell identification test 
US 
United States 
UVA 
Ultraviolet A 
UVB 
Ultraviolet B 
CCI 
WBC 
white blood cell 
WOCBP 
women of child-bearing potential 
WONCBP 
women of non-childbearing potential 
Wt 
wild-type 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 142 
 
 
11. REFERENCES 
1. 
Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven 
by type 2 cytokines, JCI Insight. 2018; 3. 
 
2. 
Betts A, Keunecke A, van Steeg TJ, et al. Linear pharmacokinetic parameters for 
monoclonal antibodies are similar within a species and across different pharmacological 
targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 
transgenic mouse using a population-modeling approach, MAbs. 2018; 10: 751-64. 
 
3. 
Chan IS, and Zhang Z. Test-based exact confidence intervals for the difference of two 
binomial proportions, Biometrics. 1999; 55: 1202-9. 
 
4. 
Charman CR, Venn AJ, and Williams HC. The patient-oriented eczema measure: 
development and initial validation of a new tool for measuring atopic eczema severity 
from the patients' perspective, Arch Dermatol. 2004; 140: 1513-9. 
 
5. 
Cooper KD. Atopic dermatitis: recent trends in pathogenesis and therapy, J Invest 
Dermatol. 1994; 102: 128-37. 
 
6. 
Cully M. Inflammatory diseases: Anti-CD1a antibody reduces inflammation in 
psoriasis, Nat Rev Drug Discov. 2016; 15: 678. 
 
7. 
de Jong A, Cheng TY, Huang S, et al. CD1a-autoreactive T cells recognize natural skin 
oils that function as headless antigens, Nat Immunol. 2014; 15: 177-85. 
 
8. 
Dirks NL, and Meibohm B. Population pharmacokinetics of therapeutic monoclonal 
antibodies, Clin Pharmacokinet. 2010; 49: 633-59. 
 
9. 
European Medicines Agency. EMA Guideline on strategies to identify and mitigate 
risks for first-in-human and early clinical trials with investigational medicinal products. 
2017. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline- 
strategies-identify-mitigate-risks-first-human-early-clinical-trials- 
investigational_en.pdf. 
 
10. Hanifin JM, Thurston M, Omoto M, et al. The eczema area and severity index (EASI): 
assessment of reliability in atopic dermatitis. EASI Evaluator Group, Exp Dermatol. 
2001; 10: 11-8. 
 
11. Jarrett R, Salio M, Lloyd-Lavery A, et al. Filaggrin inhibits generation of CD1a neolipid 
antigens by house dust mite-derived phospholipase, Sci Transl Med. 2016; 8: 325ra18. 
 
12. Juniper EF, Bousquet J, Abetz L, et al. Identifying 'well-controlled' and 'not 
well-controlled' asthma using the Asthma Control Questionnaire, Respir Med. 2006; 
100: 616-21. 


PF-07242813 
Protocol C4461001 
Final Protocol Amendment 2, 10 July 2021 
PFIZER CONFIDENTIAL 
Page 143 
 
 
13. Kim JH, Hu Y, Yongqing T, et al. CD1a on Langerhans cells controls inflammatory 
skin disease, Nat Immunol. 2016; 17: 1159-66. 
 
14. Leach MW, D OC, Dudal S, et al. Strategies and Recommendations for Using a Data- 
Driven and Risk-Based Approach in the Selection of First-in-Human Starting Dose: An 
International Consortium for Innovation and Quality in Pharmaceutical Development 
(IQ) Assessment, Clin Pharmacol Ther. 2020. 
 
15. Oyoshi MK, He R, Kumar L, et al. Cellular and molecular mechanisms in atopic 
dermatitis, Adv Immunol. 2009; 102: 135-226. 
 
16. Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on 
validity and reliability of the visual analogue scale, numerical rating scale and verbal 
rating scale in 471 patients with chronic pruritus, Acta Derm Venereol. 2012; 92: 502-7. 
 
17. Posner K, Oquendo MA, Gould M, et al. Columbia Classification Algorithm of Suicide 
Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal 
risk analysis of antidepressants, Am J Psychiatry. 2007; 164: 1035-43. 
 
18. Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the 
definition and management of anaphylaxis: summary report--Second National Institute 
of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium, 
J Allergy Clin Immunol. 2006; 117: 391-7. 
 
19. Siegfried E, Korman N, Molina C, et al. Safety and efficacy of early intervention with 
pimecrolimus cream 1% combined with corticosteroids for major flares in infants and 
children with atopic dermatitis, J Dermatolog Treat. 2006; 17: 143-50. 
 
20. Williams HC. Clinical practice. Atopic dermatitis, N Engl J Med. 2005; 352: 2314-24. 


 
 
 
Document Approval Record 
 
 
C4461001 Protocol Amendment 2 Clean 10 July 2021 
 
C4461001 Protocol Amendment 2 Clean 10 July 2021 
 
 
PPD 
 
 
PPD 
 
Document Name: 
Document Title: 
Signed By: 
Date(GMT) 
Signing Capacity 

SAP_001.pdf: 
Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 1 
TMF Doc ID: 98.03 
 
 
 
 
 
 
 
 
 
Protocol C4461001 
 
 
 
 
A PHASE 1 FIRST IN HUMAN, RANDOMIZED, DOUBLE BLIND, SPONSOR 
OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE 
ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF 
PF-07242813 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH ATOPIC 
DERMATITIS 
 
 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
 
 
 
 
Version: 
2 
Date: 
30 Oct 2022 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 2 
TMF Doc ID: 98.03 
 
 
TABLE OF CONTENTS 
LIST OF TABLES .....................................................................................................................5 
LIST OF FIGURES ....................................................................................................................5 
APPENDICES ............................................................................................................................5 
1. VERSION HISTORY ............................................................................................................6 
2. INTRODUCTION ..................................................................................................................6 
2.1. Study Objectives, Endpoints, and Estimands ............................................................7 
2.1.1. Primary Estimand(s): Healthy Adult Participants .......................................11 
2.1.2. Secondary Estimand(s): Atopic Dermatitis Participants .............................11 
CCI 
 
2.2. Study Design ............................................................................................................12 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS .................................................................................................................13 
3.1. Endpoint(s): Part 1 - Healthy Adult Participants .....................................................13 
3.1.1. Primary Endpoint(s) ....................................................................................13 
3.1.2. Secondary Endpoint(s) ................................................................................13 
CCI 
 
3.2. Endpoint(s): Part 2 - Atopic Dermatitis Participants ...............................................14 
3.2.1. Primary Endpoint(s) ....................................................................................14 
3.2.2. Secondary Endpoint(s) ................................................................................14 
CCI 
 
3.3. Baseline Variables ...................................................................................................15 
3.4. Safety Endpoints ......................................................................................................15 
3.4.1. Adverse Events ...........................................................................................16 
3.4.2. Laboratory Data ..........................................................................................16 
3.4.3. Vital Signs, including Height and Weight ...................................................17 
3.4.4. Physical Examinations ................................................................................17 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) ...................................................17 
4.1. Treatment Misallocation ..........................................................................................17 
4.2. Protocol Deviations .................................................................................................18 
5. GENERAL METHODOLOGY AND CONVENTIONS ....................................................18 
5.1. Hypotheses and Decision Rules ..............................................................................18 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 3 
TMF Doc ID: 98.03 
 
 
5.1.1. Part 1 - Healthy Adult Participants .............................................................18 
5.1.1.1. Statistical Hypotheses ................................................................18 
5.1.1.2. Statistical Decision Rules ..........................................................18 
5.1.2. Part 2 - Atopic Dermatitis Participants .......................................................18 
5.2. General Methods ......................................................................................................19 
5.2.1. Statistical Method: Part 1 - Healthy Participants Single and Multiple 
Ascending Dose ...............................................................................................19 
5.2.2. Analyses for Binary Endpoints: Part 2 – Atopic Dermatitis 
Participants .......................................................................................................19 
5.2.3. Analyses for Continuous Endpoints: Part 2 - Atopic Dermatitis 
Participants .......................................................................................................19 
5.2.4. Analyses for Categorical Endpoints: Part 2 - Atopic Dermatitis 
Participants .......................................................................................................19 
5.2.5. Analyses for Time-to-Event Endpoints: Part 2 – Atopic Dermatitis 
Participants .......................................................................................................20 
5.3. Methods to Manage Missing Data ...........................................................................20 
5.3.1. PK Data .......................................................................................................20 
5.3.1.1. Concentrations Below the Limit of Quantification ....................20 
5.3.1.2. Deviations, Missing Concentrations and Anomalous 
Values ................................................................................................20 
5.3.1.3. Pharmacokinetic Parameters ......................................................20 
5.3.2. Efficacy Data ...............................................................................................20 
6. ANALYSES AND SUMMARIES .......................................................................................22 
6.1. Part 1: Healthy Adult Participants ...........................................................................22 
6.1.1. Primary Endpoint(s) ....................................................................................22 
6.1.1.1. Safety Summaries and Analyses ................................................22 
6.1.2. Pharmacokenetic Endpoints ........................................................................24 
6.1.3. Tertiary/Exploratory Endpoint(s) ................................................................27 
6.2. Part 2: Atopic Dermatitis Participants .....................................................................28 
6.2.1. Secondary Endpoint (s): Percentage Change from Baseline in EASI 
Score at Week 6 ................................................................................................28 
6.2.1.1. Main Analysis ............................................................................28 
CCI 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 4 
TMF Doc ID: 98.03 
 
 
 
CCI 
6.2.3. Baseline and Other Summaries and Analyses ............................................. 31 
6.2.3.1. Baseline Summaries ................................................................... 31 
6.2.4. Study Conduct and Participant Disposition ................................................ 32 
6.2.5. Study Treatment Exposure .......................................................................... 32 
6.2.6. Concomitant Medications and Nondrug Treatments .................................. 32 
6.2.7. Subset Analyses .......................................................................................... 32 
6.3. Safety Summaries and Analyses .............................................................................. 32 
6.3.1. Adverse Events ........................................................................................... 32 
6.3.2. Immune-based AEs ..................................................................................... 33 
6.3.3. Laboratory Data .......................................................................................... 33 
6.3.4. Vital Signs ................................................................................................... 33 
6.3.5. Electrocardiograms ...................................................................................... 33 
6.3.6. Physical Examination .................................................................................. 33 
7. INTERIM ANALYSES ....................................................................................................... 34 
7.1. Introduction .............................................................................................................. 34 
7.2. Interim Analyses and Summaries ............................................................................ 34 
8. REFERENCES ..................................................................................................................... 34 
9. APPENDICES ...................................................................................................................... 35 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 5 
TMF Doc ID: 98.03 
 
 
LIST OF TABLES 
Table 1. 
Summary of Changes ..................................................................................6 
Table 2. 
Serum PK Parameters (Part 1) ..................................................................25 
Table 3. PK Parameters to be Summarized Descriptively .......................................................26 
 
 
LIST OF FIGURES 
Figure 1. 
C4461001 Study Design ...........................................................................13 
 
 
APPENDICES 
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern ......35 
Appendix 2. Summary of Efficacy Analyses ...........................................................................36 
Appendix 3. Data Derivation Details .......................................................................................37 
Appendix 3.1. Definition and Use of Visit Windows in Reporting ..........................................37 
Appendix 3.2. Definition and Use of Visit Windows in pruritus NRS ....................................37 
Appendix 4. Eczema Area and Severity Index (EASI) ............................................................39 
Appendix 5. Patient Reported Outcomes .................................................................................43 
Appendix 5.1. Peak Pruritis Numerical Severity Scale (PP-NRS) ...........................................43 
Appendix 5.1.1. Patient-Oriented Eczema Measure (POEM) ..................................................45 
Appendix 5.1.2. Dermatology Life Quality Index (DLQI) ......................................................46 
Appendix 6. SAS Code for Estimand 1 – Percentage Change from Baseline in EASI 
Score .........................................................................................................48 
Appendix 7. Longitudinal Mixed Model Repeated Model ......................................................50 
Appendix 8. SAS Code for the Generalized Linear Mixed Model for Binary 
Longitudinal Data ......................................................................................51 
Appendix 9. SAS Code for Estimand 2 – Risk Difference using Chan and Zhang 
(1999)2 ...................................................................................................................................................... 52 
Appendix 10. SAS Code for the Confidence Interval of a Binomial Proportion 
(Blyth-Still-Casella) ..................................................................................53 
Appendix 11. List of Abbreviations .........................................................................................54 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 6 
TMF Doc ID: 98.03 
 
 
 
1. VERSION HISTORY 
 
Table 1. 
Summary of Changes 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1 
30 NOV 2020 
Original 
30 Sep 2020 
N/A 
N/A 
2 
01 Sep 2022 
Protocol 
Amendment 2 
10 Jul 2021 
To be 
consistent 
with 
Protocol 
Amendmen 
t 2 
1. Section 6.2.2. Added details of NRS 
endpoint analysis. 
2. Section 6.2.5. Removed the 
summary of dosing compliance 
according study team agreement. 
3. Section 6.3. Added details of 
immune-based AEs. 
4. Section 6.3.4. Modified the language 
of vital signs analysis. 
5. Appendix 3. Visit window was 
updated and added window 
definition for NRS endpoints. 
6. Appendix 6. Modified the SAS code 
for Estimand 1 to be consistent with 
Section 6.2. 
 
2. INTRODUCTION 
PF-07242813 is an anti-CD1a antibody that is being developed as a treatment for patients 
with moderate to severe atopic dermatitis. 
 
This is the first time PF-07242813 will be given to humans. The purpose of the study is to 
evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses 
of PF-07242813 in healthy participants and in participants with moderate to severe atopic 
dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in 
participants with moderate to severe AD, including potential effects on clinical signs and 
symptoms. 
 
AD is a common inflammatory skin disease, especially in children with a prevalence of 
5-20% and ~11% in the total population of the US (Oyoshi et al. 2009; Williams 2005). 
Current treatments for AD include emollients, and topical anti-inflammatory agents such as 
corticosteroids and calcineurin inhibitors. These agents have generally been unsatisfactory 
for the treatment of moderate to severe disease. More recently, an injectable monoclonal 
antibody directed against the IL-4 receptor α (dupilumab) that blocks the binding of IL-4 
and IL-13 has been approved for the treatment of moderate to severe AD. While dupilumab 
represents a considerable advance in the treatment of AD, not all patients respond well or 
achieve completely clear skin. Moreover, some patients may become refractory to dupilumab 
with prolonged dosing. Additional treatments are needed that are complementary to 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 7 
TMF Doc ID: 98.03 
 
 
 
currently approved drugs that increase the proportion of patients achieving complete 
resolution of skin inflammation and / or are effective in patients who do not respond or 
become refractory to dupilumab. 
 
CD1a is an MHC class I-like molecule expressed on Langerhans cells in the skin. CD1a 
presents lipid antigens found in the skin which can be recognized by antigen-specific T cells, 
leading to subsequent T cell activation (de Jong et al. 2014). Emerging data suggest that 
pathogenic lipids, signaling through CD1a, may be important drivers of inflammation in AD 
(Berdyshev et al. 2018; Cooper 1994; Cully 2016; Jarrett et al. 2016; Kim et al. 2016). 
 
PF-07242813 is a novel humanized monoclonal antibody that binds CD1a protein with high 
affinity and selectivity. PF-07242813 prevents CD1a from interacting with T cell receptors, 
leading to the inhibition of T cell activation. Therfore, PF-07242813 would be expected to 
inhibit T cell activation and downstream proinflammatory signaling. This mechanism would 
be distinct from currently available treatments that are either broadly immunosuppressive 
(eg, corticosteroids and calcineurin inhibitors) or specifically targeted to type 2 
inflammation (eg, dupilumab). 
 
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C4461001. 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 
Objectives and Endpoints Part 1 (Healthy Adult Participants) 
 
Objectives 
Endpoints 
Primary: 
Primary: 
To evaluate the safety and tolerability of 
PF-07242813, following single and multiple doses 
in healthy adults and participants with AD. 
Incidence of treatment-emergent adverse events (AEs 
and SAEs); vital signs, safety laboratory tests, cardiac 
telemetry (SAD only), and ECG. 
Secondary: 
Secondary: 
To characterize the serum exposure of 
PF-07242813, following single and multiple doses 
in healthy adults and participants with AD. 
PF-07242813 serum exposure as data permit: AUClast, 
AUCinf, Cmax, Tmax and t1/2 after single doses; AUCτ, 
Cmax, and Tmax after each repeated dose; and t1/2 after 
the last repeated dose. 
CCI 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 8 
TMF Doc ID: 98.03 
 
 
 
 
 
 
Objectives, Endpoints and Estimands Part 2: Atopic Dermatitis Participants 
 
Objectives 
Endpoints 
Estimands 
Primary: 
Primary: 
Primary: 
To evaluate the safety and 
tolerability of PF-07242813 
versus placebo, in 
participants with moderate to 
severe AD. 
Incidence of treatment-emergent 
adverse events (AEs and SAEs); vital 
signs, safety laboratory tests, and 
ECG. 
There is no defined estimand for 
these endpoints; they will be 
analyzed using CaPS as applicable. 
Secondary: 
Secondary: 
Secondary: 
To compare the efficacy of 
PF-07242813 versus placebo 
on percent change from 
baseline in Eczema Area and 
Severity Index (EASI) in 
participants with moderate 
to severe 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 study intervention on a 
continuous endpoint; without 
prohibited medications during 
treatment. 
Study Intervention: PF-07242813 or 
placebo. 
Population: Participants with 
moderate to severe AD as defined by 
the inclusion and exclusion criteria. 
Variable: Percent change from 
baseline in EASI total score at 
Week 6. 
Intercurrent Events: 
a. 
Prohibited medications – all 
scores in participants who 
receive prohibited medication 
post randomization to Week 6 
will be omitted from the analysis 
and treated as missing scores. 
 
 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 9 
TMF Doc ID: 98.03 
 
 
 
Objectives 
Endpoints 
Estimands 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI 
 
Missing scores will be imputed 
based on the assumption that 
participants do not benefit from 
the study intervention. 
b. 
Inadequate compliance – 
participants data will be used as 
recorded. 
Events a and b are stated with 
precedence in descending order. 
Population level summary: 
The percent change from baseline 
mean difference between 
PF-07242813 and placebo in EASI 
score. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 10 
TMF Doc ID: 98.03 
 
 
 
Objectives 
Endpoints 
Estimands 
 
 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI 
α 
γ 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 11 
TMF Doc ID: 98.03 
 
 
 
 
 
 
 
2.1.1. Primary Estimand(s): Healthy Adult Participants 
There is no defined estimand; the data will be analyzed using CaPS as applicable. 
 
2.1.2. Secondary Estimand(s): Atopic Dermatitis Participants 
Estimand E1: This estimand is intended to provide a population level estimate of the 
treatment effect of the study intervention on a continuous endpoint; without prohibited 
medications during treatment. For example: 
 
• Study Intervention: PF-07242813 or placebo. 
• Population: Participants with moderate to severe AD as defined by the inclusion and 
exclusion criteria. 
 
• Variable: Percent change from baseline in EASI total score at Week 6. 
• Intercurrent Events: 
a. Prohibited medications – all scores in participants who receive prohibited 
medication post randomization to Week 6 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 study intervention. 
 
b. Inadequate compliance – participants data will be used as recorded. 
Events a and b are stated with precedence in descending order. 
Estimands 
Endpoints 
Objectives 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 12 
TMF Doc ID: 98.03 
 
 
 
• Population level summary: The percent change from baseline mean difference 
between PF-07242813 and placebo in EASI score. 
CCI 
 
 
 
 
 
 
 
 
 
 
 
2.2. Study Design 
This is a first-in-human (FIH) study of PF-07242813 that will be conducted in 2 parts: Part 1 
will be conducted in healthy adult participants and Part 2 will be conducted in participants 
with moderate to severe AD (see Figure 1). 
 
Part 1 is within-cohort randomized, participant- and investigator-blind, sponsor-open, 
placebo-controlled investigation of the safety, tolerability, PK, and immunogenicity 
following single and multiple ascending doses of PF-07242813 in healthy participants. Part 1 
will also include a cohort of Japanese healthy adult participants (Cohort 15) to provide 
safety, tolerability, and PK data in Japanese population to enable the inclusion of Japanese 
participants in future clinical trials. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 13 
TMF Doc ID: 98.03 
 
 
 
Part 2 is a randomized, participant- and investigator-blind, sponsor-open, placebo-controlled 
investigation of the safety, tolerability, PK, and pharmacodynamics (including clinical 
effects) of PF-07242813 in participants with moderate to severe atopic dermatitis (AD). The 
first cohort in Part 2 (Cohort 9) will enroll 24 participants for the assessment of the clinical 
effects of PF-07242813 in AD and exploratory evaluations of pharmacodynamic activity. 
The number of participants enrolled in Cohort 9 will provide the total sample size (N=24) for 
statistical evaluation of the primary efficacy endpoint (placebo-corrected percent change 
from baseline in continuous EASI). Participants in Cohort 9 will receive the MTD defined in 
Part 1. 
 
Figure 1. 
C4461001 Study Design 
 
 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
For the SAD/MAD and atopic dermatitis cohorts, baseline is defined as the last pre-dose 
measurement. 
 
3.1. Endpoint(s): Part 1 - Healthy Adult Participants 
3.1.1. Primary Endpoint(s) 
• Incidence of treatment-emergent adverse events (AEs and SAEs); vital signs, safety 
laboratory tests, cardiac telemetry (SAD only), and ECG. 
 
3.1.2. Secondary Endpoint(s) 
• PF-07242813 serum exposure as data permit: AUClast, AUCinf, Cmax, Tmax and t1/2 
after single doses; AUCτ, Cmax, and Tmax after each repeated dose; and t1/2 after the 
last repeated dose. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 14 
TMF Doc ID: 98.03 
 
 
 
3.1.3. Other Endpoint(s): Tertiary/Exploratory 
• PF-07242813 PK parameters, as data permit: AUClast, dose normalized (dn), 
AUCinf(dn), Cmax(dn), CL and Vz/F/Vss after single doses; AUCinf(dn), Cmax (dn) after 
each repeated dose; CL/F, CL, Vz/F, accumulation ratio, peak to trough ratio (PTR) 
after the last repeated dose. F for SC administration. 
 
• Incidence of the development of ADA and, if appropriate, NAb against PF-07242813 
following single and multiple doses. 
 
• Change from baseline in select anterior pituitary hormones levels and hormones 
regulated by them in blood that may include (but may not be limited to): HGH, 
IGF-1, TSH, T4 and Cortisol. 
 
• Change from baseline in blood cytokine levels that may include, but not be limited to, 
TNFα, IL-6 and IFNγ if performed in concordance with clinical symptoms of cytokine 
release. 
 
3.2. Endpoint(s): Part 2 - Atopic Dermatitis Participants 
3.2.1. Primary Endpoint(s) 
• Incidence of treatment-emergent adverse events (AEs and SAEs) 
• Vital signs (blood pressure, pulse rate, respiratory rate, and temperature). 
• Safety laboratory tests: Incidence and magnitude of clinical laboratory abnormalities 
including hematology blood chemistry, and urinalysis. 
 
• ECG. 
3.2.2. Secondary Endpoint(s) 
• Percent change from baseline in EASI total score at Week 6. 
3.2.3. Other Endpoint(s): Tertiary/Exploratory 
• Serum PF-07242813 concentrations after administration will be determined by a 
validated assay. 
 
• 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 time 
points specified in the SoA. 
 
• Percent change from baseline in EASI total score at time points in the SoA. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 15 
TMF Doc ID: 98.03 
 
 
 
• Proportion of participants with moderate to severe AD achieving EASI-50/EASI-75/ 
EASI-90/EASI-100 (respectively 50%, 75%, 90%, and 100% improvement from 
baseline), at Week 6 and other time points specified in SOA. 
 
• Incidence of development of antidrug antibodies (ADAs) and if appropriate, 
neutralizing antibodies (NAbs). 
 
• Change from baseline in select anterior pituitary hormones levels and hormones 
regulated by them in blood that may include (but may not be limited to): HGH, 
IGF-1, TSH, T4 and Cortisol. 
 
• Change from baseline in blood cytokine levels that may include, but not be limited to, 
TNFα, IL-6 and IFNγ if performed in concordance with clinical symptoms of cytokine 
release. 
 
• Change from baseline in circulating biomarkers which may include Total IgE, TARC 
(CCL17), IL-31, IL-17A, eosinophils and lymphocyte subsets. 
 
• Change from baseline in gene expression and/or histological endpoints may be 
measured from skin biopsies. 
 
• Change from baseline in Patient-Oriented Eczema Measure (POEM) at Week 6 and 
at all other time points specified in the SoA. 
 
• Change from baseline in Dermatology Life Quality Index (DLQI) at Week 6 and at all 
other time points specified in the SoA. 
 
• Change from baseline in pruritus severity and frequency in Pruritus Numeric Rating 
Scale) at Week 6 and at all other time points specified in the SoA. 
 
3.3. Baseline Variables 
In general, for all analyses, baseline will be defined based on observations collected prior to 
first dose. Baseline values for demographics, medical and other history, atopic dermatitis 
history will be based on measures collected at Visit 1/Screening visit. Study Day 1 is defined 
as the day the subject receives first dose of study drug. For purposes of all other analyses 
including analyses for change from baseline, the baseline value will be defined as measured 
on Day 1 predose. If a value is missing on Day 1, then the last available observation before 
Day 1 will be used. 
 
3.4. 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: 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 16 
TMF Doc ID: 98.03 
 
 
 
• 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). 
 
3.4.1. 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. 
 
A 3-tier approach will be used to summarize AEs. Under this approach, AEs are classified 
into 1 of 3 tiers. Different analyses will be performed for different tiers (see Section 6.3.1). 
 
Tier 1 events: These are prespecified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan. 
 
Tier 2 events: These are events that are not tier 1 but are “common.” A Medical Dictionary 
for Regulatory Activities (MedDRA) preferred term (PT) is defined as a Tier 2 event if there 
are at least 4 in any treatment group. 
 
Tier 3 events: These are events that are neither Tier 1 nor Tier 2 events. 
 
3.4.2. Laboratory Data 
Below is a list of hematology and serum chemistry test parameters. 
 
• Hematology: hemoglobin, hematocrit, red blood cell count, reticulocyte count, 
platelet count, white blood cell count with differential, total neutrophils, eosinophils, 
monocytes, basophils, lymphocytes, coagulation panel. 
• Serum chemistry: blood urea nitrogen, creatinine, creatine phosphokinase, glucose, 
sodium, potassium, chloride, calcium, total bicarbonate, aspartate aminotransferase, 
alanine aminotransferase, gamma-glutamyl transferase, bilirubin, alkaline 
phosphatase, lactate dehydrogenase, uric acid, albumin, total protein, total 
cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), 
triglycerides, cystatin C. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 17 
TMF Doc ID: 98.03 
 
 
 
3.4.3. Vital Signs, including Height and Weight 
Vital sign measurements are oral, temporal or tympanic temperature, provided the same 
method is used consistently throughout the study, respiratory rate, pulse rate, and blood 
pressures. 
 
Weights are collected at the baseline. 
 
3.4.4. Physical Examinations 
A full physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung 
examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The 
limited or abbreviated physical examination will be focused on general appearance including 
skin (specific attention to infusion and injection site reactions), the respiratory, 
gastrointestinal, and cardiovascular systems, as well as towards participant reported 
symptoms. 
 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) 
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures. 
 
Population 
Description 
Modified Intention to 
Treat (mITT) 
All participants randomly assigned to study intervention and 
who apply at least 1 dose of study intervention. 
PK concentration set 
All enrolled participants who applied at least one dose of 
PF-07242813 and in whom at least once concentration value is 
reported. 
PK parameters 
The PK parameter analysis population will be defined as all 
randomized participants who received at least 1 dose of study 
intervention and who have at least 1 of the PK parameters of 
interest calculated. 
Safety Analysis Set 
All participants randomly assigned to study intervention and 
who receive at least 1 dose of study intervention. Participants 
will be analyzed according to the product they actually 
received. 
 
4.1. Treatment Misallocation 
All analyses will be performed on an “as-treated” basis and will not include data from 
participants who are randomized but not treated. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 18 
TMF Doc ID: 98.03 
 
 
 
If a participant takes a treatment that is not consistent with the treatment they are randomized 
to, for example takes a treatment out of sequence or takes the same treatment twice, then they 
will be reported under the treatment that they actually receive for all safety, PK and 
pharmacodynamic analyses, where applicable. 
 
4.2. Protocol Deviations 
Participants who experience events that may affect their PK profile may be excluded from 
the PK analysis. At the discretion of the pharmacokineticist, a concentration value may also 
be excluded if the deviation in sampling time is of sufficient concern or if the concentration 
is anomalous for any other reason. 
 
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure. 
 
5. GENERAL METHODOLOGY AND CONVENTIONS 
The primary analysis of atopic dermatitis cohort 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 
5.1.1. Part 1 - Healthy Adult Participants 
5.1.1.1. Statistical Hypotheses 
No classical hypothesis testing will be performed. 
 
5.1.1.2. Statistical Decision Rules 
Not applicable. 
 
5.1.2. Part 2 - Atopic Dermatitis Participants 
Statistical inference will be made on the secondary endpoint: (percentage change from 
baseline in EASI score at Week 6). The null hypothesis is that there is no difference between 
the treatment group and the placebo group. The alternative hypothesis is that the treatment 
group (PF-07242813 arm) is superior to the placebo group at Week 6. The study will be 
considered positive, if this null hypothesis is rejected. 
 
The sample size calculation is based on the secondary endpoint (percent change from 
baseline in EASI score at Week 6). A total of 24 randomized participants with a 
randomization ratio of 2:1 into the treatment and placebo group will provide approximately 
80% power to detect a difference of 50 in percent change from baseline with a common 
standard deviation 46% between PF-07242813 and the placebo arm with 1-sided 
alpha=0.05. 
 
Cohort 9 will enroll 24 participants with moderate to severe AD at the MTD. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 19 
TMF Doc ID: 98.03 
 
 
 
5.2. General Methods 
5.2.1. Statistical Method: Part 1 - Healthy Participants Single and Multiple Ascending 
Dose 
Given the exploratory nature, descriptive statistics and graphic visualization will be provided 
for these segments. No formal statistical hypothesis testing is planned. 
 
5.2.2. Analyses for Binary Endpoints: Part 2 – Atopic Dermatitis Participants 
Landmark (cross-sectional) analyses of key binary endpoints will calculate and test for risk 
differences using the method of Chan and Zhang (1999).2 Risk differences, 90% confidence 
interval and 1-sided p-value will be presented. 
 
For all binary endpoints, a summary based on the mITT Observed Efficacy Set 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. 
 
Exploratory categorical analyses that include or assess the effects of covariates may be done 
on an exploratory basis. Exploratory longitudinal analyses may also be performed 
 
5.2.3. Analyses for Continuous Endpoints: Part 2 - Atopic Dermatitis Participants 
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 (Weeks 1, 2, 3, 4, and 6), 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 percentage 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-07242813 and the placebo arm will be derived from the model. 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 the following: 
n, mean, median, standard deviation, minimum and maximum. 
 
5.2.4. Analyses for Categorical Endpoints: Part 2 - Atopic Dermatitis Participants 
NA. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 20 
TMF Doc ID: 98.03 
 
 
 
5.2.5. Analyses for Time-to-Event Endpoints: Part 2 – Atopic Dermatitis Participants 
NA. 
 
5.3. Methods to Manage Missing Data 
5.3.1. PK Data 
5.3.1.1. Concentrations Below the Limit of Quantification 
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. (In listings BLQ values will be reported as “<LLQ”,where LLQ 
will be replaced with the value for the lower limit of quantification). 
 
5.3.1.2. Deviations, Missing Concentrations and Anomalous Values 
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if any of the following cases is true: 
 
• A concentration has been collected as ND (ie, not done) or NS (ie, no sample); 
• A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist. 
 
Note that summary statistics will not be presented at a particular time point if more than 
50% of the data are missing. 
 
5.3.1.3. Pharmacokinetic Parameters 
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a participant’s concentration data, the parameter will be coded as NC 
(ie, not calculated). (Note that NC values will not be generated beyond the day that a 
participant discontinues). 
 
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular dose level with ≥3 evaluable measurements. 
 
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event), this will be footnoted in summary tables and will not be included in 
the calculation of summary statistics or statistical analyses. 
 
5.3.2. Efficacy Data 
The following patient level data descriptions are also required for defining the pre-specified 
analyses: 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 21 
TMF Doc ID: 98.03 
 
 
 
Defined Analysis Data 
set (at the data level) – 
endpoint specific 
Description 
Primary Estimand 
Continuous Endpoint Set 
This set will include all patients in the mITT population. All 
data for a subject after the initiation of prohibited medications 
will be set to missing. 
Note the primary estimand requires multiple imputation which 
will be performed on this dataset, the multiple imputations 
themselves will not be saved in the database, however, the 
SAS specifications and random number seed will be. 
Secondary Estimand 
Categorical Endpoint Set 
This set will include all patients in the mITT population. All 
data for a subject after the initiation of prohibited medications, 
withdrawal of either study drug or the study itself will be set to 
a failure. Any other additional missing data will be recorded as 
a failure. Subjects will have either a success or failure in the 
dataset for all scheduled visits. 
Observed Efficacy Set 
This set will include all patients in the mITT population and all 
observed data and includes all data recorded from the CRF 
pages. No data will be set to missing or modified from the 
original CRF record. 
 
The primary analysis will use the primary estimand continuous endpoint set. For each 
landmark analysis (eg, Cross sectional analysis by week) missing data will imputed using a 
control-based imputation method. PROC MI will first be called at the visit and a control- 
based method (implemented with the missing not at random (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. Imputation will use the full conditional specification (FCS) method, the imputed 
data for the treatment and placebo arms will be combined for the analysis. 
 
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 will have been set to a 
failure. Summaries will use the Observed Efficacy Set and will report results on an observed 
case (OC) basis. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 22 
TMF Doc ID: 98.03 
 
 
 
6. ANALYSES AND SUMMARIES 
6.1. Part 1: Healthy Adult Participants 
6.1.1. Primary Endpoint(s) 
6.1.1.1. Safety Summaries and Analyses 
All safety analyses will be performed on the safety population. 
 
All safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, categorical summaries, and graphical presentations. Change from 
baseline on laboratory data and vital signs will be additionally summarized. Participant 
listings will also be produced for these safety endpoints. 
 
6.1.1.1.1. Adverse Events 
An adverse event is 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. Events that occur in a non-treatment period (follow-up or washout period) will be 
counted as treatment emergent and attributed to the previous treatment taken. 
 
6.1.1.1.2. Laboratory Data 
Safety laboratory tests will be performed as described in the protocol. To determine if there 
are any clinically significant laboratory abnormalities, the hematological, clinical chemistry 
(serum) and urinalysis safety tests will be assessed against the criteria specified in the 
sponsor reporting standards. The assessment will take into account whether each participant’s 
baseline test result is within or outside the laboratory reference range for the particular 
laboratory parameter. Baseline of safety laboratory tests will be the last pre-dose 
measurement. 
 
6.1.1.1.3. Vital Signs 
Single supine blood pressure (both diastolic and systolic), pulse rate, respiratory rate and/or 
temperature will be collected at times specified in the Schedule of Activities in the protocol. 
 
The following vital signs endpoints will be determined and summarized for each treatment 
group. 
 
• Actual values, change from baseline in supine blood pressure, pulse rate, respiratory 
rate and temperature over all measurements taken postdose; 
 
• The maximum decrease and increase from baseline over all measurements taken 
postdose for supine blood pressure. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 23 
TMF Doc ID: 98.03 
 
 
 
Baseline will be defined as the last pre-dose recording. The increase from baseline will be 
calculated by subtracting the baseline value from each post-dose measurement to give the 
change from baseline for each participant. The maximum of these values over the duration of 
dosing will be reported as maximum increase from baseline, except where a participant does 
not show an increase. In such an instance, the minimum decrease will be reported. 
 
Similarly, decrease from baseline will be calculated by subtracting each post-dose 
measurement from individual participant’s baseline value. Maximum decrease from baseline 
will be reported as the minimum value of the changes from baseline. In cases where a 
participant does not show a decrease, the minimum increase will be reported. 
 
Maximum absolute values and changes from baseline for vital signs will also be tabulated by 
treatment using categories as defined in Appendix 1. 
 
6.1.1.1.4. Electrocardiograms 
The QT, QTc, PR, heart rate (HR) and QRS complex will be recorded at each assessment 
time, as specified in the Schedule of Activities. 
 
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula: 
 
QTcF = QT 
(RR)l/3 
 
where RR = 60/HR(if not provided). 
 
The average of the triplicate ECG measurements collected before dose administration on 
Day 1 of each cohort will serve as each participant’s baseline value. 
 
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. 
 
Changes from baseline will be defined as the change between postdose ECG parameter 
values and the baseline. If triplicate postdose measurements are collected, the average of the 
values will be used in the analysis. 
 
The maximum absolute value (post-dose) and the maximum increase from baseline for 
QTcF, QT, heart rate, PR and QRS, will be determined over all measurements taken 
post-dose and reported. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 24 
TMF Doc ID: 98.03 
 
 
 
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. 
 
If more than 1 ECG is collected at a nominal time after dose administration (for example, 
triplicate ECGs), the mean of the replicate measurements will be used to represent a single 
observation at that time point. If any of the 3 individual ECG tracings has a QTc value 
>500 msec, but the mean of the triplicates is not >500 msec, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500-msec value in appropriate clinical context. However, values from individual tracings 
within triplicate measurements that are >500 msec will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 msec. Changes 
from baseline will be defined as the change between the postdose QTc value and the average 
of the time-matched baseline triplicate values on Day -1, or the average of the predose 
triplicate values on Day 1. 
 
In addition, an attempt will be made to explore and characterize the relationship between 
serum concentration and QT interval length using a PK/PD modeling approach. If a PK/PD 
relationship is found, the impact of participant factors (covariates) on the relationship will 
be examined. 
 
In addition, PR and QRS maximum values and maximum increases from baseline will also 
be tabulated by treatment using categories as defined in Appendix 1. 
 
6.1.2. Pharmacokenetic Endpoints 
All PK analysis will be performed on the PK analysis set (see Section 4). 
 
Plasma samples will be collected as specified in the SoA of the protocol and analysed for 
PF-07242813. 
 
The PK parameters detailed in the Table 2 will be calculated for PF-07242813 (if possible) 
from the concentration-time values using standard non-compartmental methods: 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 25 
TMF Doc ID: 98.03 
 
 
 
Table 2. 
Serum PK Parameters (Part 1) 
 
Parameter 
Single Dose 
CCI 
Definition 
Method of Determination 
 
 
AUClast(dn) 
CCI 
 
Dose normalized AUClast 
 
AUClast/Dose 
 
 
 
 
AUCinf(dn)a 
Cmax 
CCI 
Tmax 
 
a 
1/2 
 
 
 
 
 
 
 
 
 
CCI 
 
Dose normalized AUCinf 
Maximum serum concentration 
 
Time for Cmax 
 
Terminal elimination half-life 
 
AUCinf/Dose 
Observed directly from data 
 
Observed directly from data as time of first 
occurrence 
Loge(2)/kel, 
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
loglinear -concentration time- curve. Only 
those data points judged to describe the 
terminal log-linear decline will be used in the 
regression 
 
 
 
 
Multiple Doses 
AUCτ 
Area under the serum 
concentration time- profile over the dosing 
interval τ where τ=2 weeks/336 hours 
CCI τ 
τ 
 
Linear/Log trapezoidal method 
Cmax 
Cmax(dn) 
CCI 
Maximum serum concentration 
Dose normalized Cmax 
Observed directly from data 
Cmax/Dose 
τ τ 
 
τ 
 
τ 
τ 
t


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 26 
TMF Doc ID: 98.03 
 
 
 
Parameter 
Definition 
Method of Determination 
a 
t1/2 
Terminal elimination half-life 
Loge(2)/kel, 
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
loglinear -concentration time- curve. Only 
those data points judged to describe the 
terminal log-linear decline will be used in the 
regression 
CCI 
 
τ 
τ 
a. 
If data permit. 
 
The PK parameters in Table 2 will be listed and summarized for participants in the PK 
parameter analysis set. Missing values will be handled as detailed in Section 5.3.1. Each PK 
parameter will be summarized by dose and will include the set of summary statistics as 
specified in the table below. 
 
Table 3. PK Parameters to be Summarized Descriptively 
 
Parameter 
Summary Statistics 
AUClast , AUCinf, 
AUCτ, AUC(dn), Cmax, 
Cmax(dn), CCI 
N, arithmetic mean, median, cv%, standard deviation, minimum, maximum, 
geometric mean and geometric cv%. 
Tmax 
N, median, minimum, maximum. 
t1/2 
N, arithmetic mean, median, cv%, standard deviation, minimum, maximum. 
 
There will be two summary tables presenting all PK parameters for SAD and MAD 
separately. They will include data from all cohorts and will be presented by dose. For the 
derivation of PK parameters, actual PK sampling times will be used. 
 
To assess the relationship between the PK parameters and dose, dose normalized AUCinf, 
AUClast and Cmax will be plotted against dose and SC or IV (using a logarithmic scale), and 
will include individual subject values and the geometric means for each dose. Geometric 
means will have a different symbol than the individual values. The values will be dose 
normalized (to a 1 mg dose) by dividing the individual values and raw geometric means by 
dose. A footnote will be added to the plots to indicate that geometric means are presented and 
that data from all cohorts are presented on the plot but SAD, MAD SC and MAD IV will be 
identified with different symbols. The SAD and MAD groups will have corresponding 
placebo groups throughout, if applicable. The PK data from Japanese cohort will be 
summarized separately. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 27 
TMF Doc ID: 98.03 
 
 
 
Supporting data from the estimation of t½ will be listed where applicable: terminal phase rate 
constant (kel); goodness of fit statistic from the log-linear regression (r2); the percent of 
AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of time points 
used in the estimation of kel. These data may be included in the clinical study report. 
 
Presentations for PF- 07242813 concentrations will include: 
 
• A listing of all concentrations sorted by subject ID, cohort (SAD or MAD), dose and 
nominal time postdose. The concentration listing will also include the actual times. 
Deviations from the nominal time will be given in a separate listing. 
 
• A summary of concentrations by cohort, dose and nominal time postdose, where the 
set of statistics will include n, mean, median, standard deviation, coefficient of 
variation (cv), minimum, maximum and the number of concentrations above the 
lower limit of quantification. 
 
• Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose by cohort and dose (all treatments on the same plot per scale, 
based on the summary of concentrations by cohort, dose and time postdose). 
 
• Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by cohort and dose (all treatments on the same plot per scale, based on 
the summary of concentrations by cohort, dose and time postdose). 
 
• Individual concentration time plots by cohort and dose (on both linear and semi-log 
scales) against actual time postdose (there will be separate spaghetti plots for each 
dose per scale). 
 
• Individual concentration time plots by subject (on both linear and semi-log scales) 
against actual time postdose [there will be separate plots for each subject (containing 
all doses) per scale]. 
 
The length of time used for the x-axes of these plots will be decided on review of the data, 
and will depend on how long PF-07242813 concentration is quantifiable in the matrix. 
 
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used. 
CCI 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 28 
TMF Doc ID: 98.03 
 
 
 
 
 
• 
 
 
 
 
 
6.2. Part 2: Atopic Dermatitis Participants 
6.2.1. Secondary Endpoint (s): Percentage Change from Baseline in EASI Score at 
Week 6 
6.2.1.1. Main Analysis 
• Estimand strategy: Estimand E1 (Section 3.1.2). 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 Primary 
Estimand Continuous Endpoint Set. 
 
• Analysis methodology: Percent change from baseline will be analyzed using an 
ANCOVA with the observed (or imputed) Week 6 percentage change from baseline 
EASI score as the dependent variable with treatment arm and baseline EASI score as 
the independent variables. 
 
• Intercurrent events and missing data: Data after study drug discontinuation and 
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 5.3.2). 
Hundred (100) 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 for percent change from 
baseline in EASI score. 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 29 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 
 
 
 
 
 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 30 
TMF Doc ID: 98.03 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 31 
TMF Doc ID: 98.03 
 
 
 
 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 32 
TMF Doc ID: 98.03 
 
 
 
6.2.4. Study Conduct and Participant Disposition 
Subjects’ evaluation, disposition and discontinuation will be summarized according to CaPS. 
 
6.2.5. Study Treatment Exposure 
The exposure to study drug will be summarized by the total number of days of dosing, 
mean/median number of days and number and percent of subjects in exposure duration 
categories. 
 
6.2.6. Concomitant Medications and Nondrug Treatments 
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to CaPS. 
 
6.2.7. Subset Analyses 
No subset analyses are planned; however the impact of different baseline subgroups on the 
primary and key secondary endpoints may be explored on ad-hoc basis, and will not be 
reported in Clinical Study Report. 
 
6.3. 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 8.2.2.5 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 5.2.2. A 3-tier approach will be used to summarize AEs. Under this 
approach, AEs are classified into 1 of 3 tiers. 
 
6.3.1. 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 5.2.2. A 3-tier approach will be used to summarize AEs. Under this 
approach, AEs are classified into 1 of 3 tiers. 
 
Tier-1 events: These are pre-specified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan. There are no Tier 1 events for this study. Tier 1 
displays will not be created. 
 
Tier-2 events: These are events that are not tier-1 but are “common”. A MedDRA Preferred 
Term (PT) is defined as a tier-2 event if there is at least 4 subjects with any event in any 
treatment group. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 33 
TMF Doc ID: 98.03 
 
 
 
Tier-3 events: These are events that are neither tier-1 nor tier-2 events. 
 
For tier-2 events, the proportion of AEs observed in each treatment groups will be presented 
along with the point estimates and associated 95% confidence intervals of the risk difference 
for each active treatment compared with placebo using the exact methods described in 
Section 5. 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. The 3-tier approach facilitates this exploratory analysis. 
 
6.3.2. Immune-based AEs 
Immune-based adverse events will be summarized by visits. If ADA results are available, 
immune-based adverse events may be summarized by categories of ADA results (for 
example, by ADA positive, negative, and not-tested categories). Immune-based adverse 
events will include infusion and injection site reaction, and clinically evaluated results of 
anaphylaxis based on the Sampson’s Criteria, and AEs based on the Anaphylactic Reaction 
Standardised MedDRA Query (SMQ), Angioedema SMQ, Hypersensitivity SMQ, cytokine 
storm, and delayed immune response. 
 
6.3.3. 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. 
 
6.3.4. Vital Signs 
Vital signs will be summarized at baseline and all visits specified in SoA. 
 
6.3.5. Electrocardiograms 
ECG parameters, if applicable, will be summarized at baseline and all visits specified in SoA. 
 
6.3.6. Physical Examination 
Physical examinations may be summarized at baseline and all-available post-baseline visits. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 34 
TMF Doc ID: 98.03 
 
 
 
7. INTERIM ANALYSES 
7.1. Introduction 
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessments, facilitating dose-escalation decisions, PK/PD modeling, 
and/or supporting clinical development. 
 
This study will not use a Data Monitoring Committee (DMC). 
 
7.2. Interim Analyses and Summaries 
NA. 
 
8. REFERENCES 
1. 
Casella G. Refining binomial confidence intervals. Can J Statist 1986; 14: 113–129.4. 
 
2. 
Chan ISF and Zhang Z. Test based exact confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999, 55:1201–1209. 
 
3. 
Mosteller RD (1987) Simplified calculation of body surface area. N Engl J Med 317 
(17): 1098 (letter). 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 35 
TMF Doc ID: 98.03 
 
 
 
9. APPENDICES 
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern 
Categories for QTcF 
Absolute value of 
QTcF (msec) 
>450 and ≤480 
>480 and ≤500 
>500 
Increase from baseline 
in QTcF (msec) 
>30 and ≤60 
>60 
 
Categories for PR and QRS 
 
PR (ms) 
max. ≥300 
PR (ms) increase 
from baseline 
Baseline >200 
and max. 
≥25% increase 
Baseline ≤200 and 
max. ≥50% 
increase 
QRS (ms) 
max. ≥140 
QRS (ms) 
increase from 
baseline 
≥50% increase 
 
Categories for Vital Signs 
 
Systolic BP (mm Hg) 
min. <90 
Systolic BP (mm Hg) 
change from baseline 
max. decrease ≥30 
max. increase ≥30 
Diastolic BP (mm Hg) 
min. <50 
Diastolic BP (mm Hg) 
change from baseline 
max. decrease ≥20 
max. increase ≥20 
Supine pulse rate (bpm) 
min. <40 
max. >120 
 
Measurements that fulfill these criteria are to be listed in report. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 36 
TMF Doc ID: 98.03 
 
 
 
Appendix 2. Summary of Efficacy Analyses 
 
Efficacy 
Endpoint 
Analysis Type 
Population 
Data Inclusion and 
Rules for Handling 
Intercurrent Events 
and Missing Data 
Analysis 
Model/Method 
Week 6 PCFBL 
in EASI 
Primary Analysis 
mITT 
MI 
ANCOVA 
All Visits IGA 
Response 
Secondary Analysis 
mITT 
NRI 
Chan and 
Zhang (1999)2 
All Visits CFBL 
PP-NRS 
Response 
Secondary Analysis 
mITT 
OD 
MMRM 
All Visits EASI – 
75 Response 
Secondary Analysis 
mITT 
NRI 
Chan and 
Zhang (1999)2 
CCI 
Main analysis 
mITT 
All data collected 
will be included 
regardless of 
intercurrent events. 
Missing data will be 
imputed. 
ANCOVA 
CCI 
PCFBL= Percent change from baseline; CFBL= Change from baseline; ANCOVA = Analysis of Covariance; 
OD = Observed data. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 37 
TMF Doc ID: 98.03 
 
 
 
Appendix 3. Data Derivation Details 
 
Appendix 3.1. Definition and Use of Visit Windows in Reporting 
 
Visit windows will be used for efficacy variables (except change from baseline in pruritus 
NRS severity and frequency), and for any safety data (except the laboratory data) that display 
or summarize by study visit. For other endpoints (eg, ECG, vital signs, Physical Exam, Skin 
tolerability etc.), 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 ≤22 
4 
Week 4 
29 
23 ≤ day ≤36 
5 
Week 6 
43 
37 ≤ day ≤50 
6 
Week 8 
57 
51 ≤ day ≤71 
7 
Week 12 
85 
72 ≤ day ≤99 
8 
Week 16 
113 
day ≥100 
* 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 by 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 equaled distant from the Target Day in absolute value, the later visit should be 
used. 
 
Appendix 3.2. Definition and Use of Visit Windows in pruritus NRS 
 
Visit Label 
Target Day 
Visit Window 
Baseline* 
1 
day = 1 
Day 2 
2 
day = 2 
Day 3 
3 
day = 3 
Day 4 
4 
day = 4 
Day 5 
5 
day = 5 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 38 
TMF Doc ID: 98.03 
 
 
 
Day 6 
6 
day = 6 
Day 7 
7 
day = 7 
Day 8 
8 
day = 8 
Day 9 
9 
day = 9 
Day 10 
10 
day = 10 
Day 11 
11 
day = 11 
Day 12 
12 
day = 12 
Day 13 
13 
day = 13 
Day 14 
14 
day = 14 
Week 2 
15 
15 ≤ day ≤ 22 
Week 4 
29 
23 ≤ day ≤ 36 
Week 6 
43 
37 ≤ day ≤ 50 
Week 8 
57 
51 ≤ day ≤ 71 
Week 12 
85 
72 ≤ day ≤ 99 
Week 16 
113 
day ≥100 
* 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 by 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 (only for Weeks 2, 4, 6, 8, 12, 16), keep the 
one closest to the Target Day. If two visits are equaled distant from the Target Day in 
absolute value, the later visit will be used. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 39 
TMF Doc ID: 98.03 
 
 
 
Appendix 4. Eczema Area and Severity Index (EASI) 
 
The EASI quantifies the severity of a subject’s atopic dermatitis based on both severity of 
lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the 
atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, 
excoriation, and lichenification (each scored separately) for each of four body regions, with 
adjustment for the percent of BSA involved for each body region and for the proportion of 
the body region to the whole body. 
 
Lesion Severity by Clinical Signs: The basic characteristics of atopic dermatitis 
lesions-erythema, induration/papulation, excoriation, and lichenification-provide a means for 
assessing the severity of lesions. Assessment of these four main clinical signs is performed 
separately for four body regions: head and neck, upper limbs, trunk (including axillae and 
groin) and lower limbs (including buttocks). Average erythema, induration/papulation, 
excoriation, and lichenification are scored for each body region according to a 4-point scale: 
0=absent; 1=mild; 2=moderate; 3=severe. Morphologic descriptors for each clinical sign 
severity score are shown in the table below. 
 
Clinical Sign Severity Scoring Criteria for the EASI 
 
Score 
Description* 
Erythema (E) 
0 
Absent 
None; may have residual discoloration (post-inflammatory hyperpigmentation 
and/or hypopigmentation). 
1 
Mild 
Light pink to light red 
2 
Moderate 
Red 
3 
Severe 
Deep, dark red 
Induration/Papulation (I) 
0 
Absent 
None 
1 
Mild 
Barely palpable to slight, but definite hard thickened skin and/or papules 
2 
Moderate 
Easily palpable moderate hard thickened skin and/or papules 
3 
Severe 
Severe hard thickened skin and/or papules 
Excoriation (Ex) 
0 
Absent 
None 
1 
Mild 
Slight, but definite linear or picked scratch marks or penetrating surface injury 
2 
Moderate 
Moderate linear or picked scratch marks or penetrating surface injury 
3 
Severe 
Severe linear or picked scratch marks or penetrating surface injury 
Lichenification (L) 
0 
Absent 
None 
1 
Mild 
Barely perceptible to slight, but definite thickened skin, fine skin markings, 
and lichenoid scale 
2 
Moderate 
Moderate thickened skin, coarse skin markings, and coarse lichenoid scale 
3 
Severe 
Severe thickened skin with very coarse skin markings and lichenoid scale 
∗ The EASI will exclude scalp, palms, and soles from the assessment/scoring. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 40 
TMF Doc ID: 98.03 
 
 
 
%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 
 
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. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 41 
TMF Doc ID: 98.03 
 
 
 
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. 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 42 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 43 
TMF Doc ID: 98.03 
 
 
1
9
8
7
6
5
4
3
2
1
0
itch 
imaginable 
itch 
 
Appendix 5. Patient Reported Outcomes 
 
Appendix 5.1. 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? 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
Worst 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 44 
TMF Doc ID: 98.03 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 45 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 46 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 47 
TMF Doc ID: 98.03 
 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 48 
TMF Doc ID: 98.03 
 
 
 
 
 
 
 
libname c4461001 "/Volumes/app/…… /data_vai" ; 
 
 
data ps; 
 
run; 
 
 
set c4461001.adps; 
 
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; 
where viswin = 9; 
keep subjid dose chg aval base; 
run; 
 
 
proc means data=ex1; 
class dose; 
var chg aval; 
run; 
 
proc sort data=ex1 out=ex2; 
*data must be sorted before using proc mi; 
by dose; 
run; 
 
*imputing aval=observed so range of endpoint 0-72 can be included in; 
*mi procedure; 
proc mi data=ex2 seed=1022 nimpute=100 out=outimp max=72 min=0; 
class dose; 
monotone regpmm(aval= base/details k=5); 
 
 
 
run; 
mnar model( aval/modelobs = (dose="0")); 
var base aval; 
 
proc univariate data=outimp; 
var aval; 
histogram ; 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 49 
TMF Doc ID: 98.03 
 
 
 
 
 
run; 
 
 
data outimp1; 
set outimp; 
chg = aval - base;**calculate chg from baseline; 
pchg=(aval-base)/base*100; **calculate pchg from baseline; 
run; 
proc sort data = outimp1 out = outimp2; 
by _imputation_ dose subjid; 
run; 
 
proc mixed data=outimp2; 
by _imputation_; 
class dose(ref='0'); 
model chg = base dose; 
lsmeans dose / diff alpha=.1; 
ods output diffs=diffs lsmeans=lsmeans; 
run; 
 
data diffsout; 
set diffs; 
**only keep within contrasts vs placebo; 
where dose = 0; 
run; 
 
**now use mianalyze on lsmean differences; 
**First sort by group, and _dose (dose = 0 for all groups); 
proc sort data=diffsout out=diffsout1; 
by _dose _imputation_; 
run; 
 
**now mianalyze by 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 _dose; 
modeleffects estimate; 
stderr stderr; 
ods output parameter 
estimates=parameterestimates; 
run; 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 50 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 51 
TMF Doc ID: 98.03 
 
 
 
 
 
 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 52 
TMF Doc ID: 98.03 
 
 
 
 
 
CCI 
 
 
 
 
 
 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 53 
TMF Doc ID: 98.03 
 
 
 
 
 
 
 
 
 
CCI 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 54 
TMF Doc ID: 98.03 
 
 
 
Appendix 11. 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 
AUC 
area under the curve 
AUC24 
area under the concentration-time curve from time 0 to 24 hours 
after dose 
AUCinf 
area under the concentration-time curve from time 0 to infinity 
AUCtau 
area under the concentration-time curve during any dosing interval 
at steady state 
AZA 
azathioprine 
BBS 
Biospecimen Banking System 
BCG 
bacille Calmette-Guerin 
β-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 
CCI 
CD 
Crohn’s disease 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CCI 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
maximum observed concentration 
CMV 
Cytomegalovirus 
CO2 
carbon dioxide (bicarbonate) 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 55 
TMF Doc ID: 98.03 
 
 
 
Abbreviation 
Term 
C I 
CT 
clinical trial 
DILI 
drug-induced liver injury 
CCI 
DNA 
deoxyribonucleic acid 
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 
EOT 
end of treatment 
ePRO 
electronic patient reported outcome 
ET 
early termination 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
I 
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 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 56 
TMF Doc ID: 98.03 
 
 
 
Abbreviation 
Term 
IFN-α 
Interferon alpha 
CCI 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 
IGRA 
Interferon Gamma Release Assay 
CCI 
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 
NOAEL 
no-observed-adverse-effect level 
NRS 
Numerical Rating Scale 
NTIS 
Night time itch scale 
CCI 
PCD 
primary completion date 
PCP 
primary care physician 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PG 
polypropyle glycol 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 57 
TMF Doc ID: 98.03 
 
 
 
Abbreviation 
Term 
PGIC 
Patient global impression of change 
PGIS 
Patient global impression of severity 
PI 
principal investigator 
PK 
pharmacokinetic(s) 
CCI 
PPD 
Purified Protein Derivative 
CCI 
PR 
pulse rate 
PRO 
Patient reported outcomes 
CCI 
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 
RBC 
red blood cell 
RNA 
ribonucleic acid 
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 
t1/2 
half-life 
TARC 
thymus- and activation-regulated chemokine 
TB 
tuberculosis 
TBili 
total bilirubin 
TdP 
Torsade de Pointes 
TEAE 
treatment emergent adverse events 
Tmax 
time taken to reach the maximum concentration 
CCI 
TYK2 
Tyrosine Kinase 2 


Protocol C4461001 (PF-07242813) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 58 
TMF Doc ID: 98.03 
 
 
 
Abbreviation 
Term 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
US 
United States 
UVA 
ultraviolet A light 
CCI 
UVB 
ultraviolet B light 
VZV 
varicella zoster virus 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential