Clinical trial NCT05650333
Conditions: Alopecia Areata
Sponsor: Pfizer
Start date: 2023-03-02; Completion date: 2023-08-11
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to evaluate the pharmacokinetics (how the medicine is changed and eliminated from your body after you take it) and pharmacodynamics (effects of the medicine in the body) of the study medicine (called Ritlecitinib) in children of 6 to \<12 years of age with Alopecia Areata, a condition of scalp hair loss. 12 children with alopecia areata will be participating in this study. All participants will receive study medicine with a dose of 20 milligram (mg) orally once daily for 7 days. 5 blood samples will be collected on day 7 for pharmacokinetic evaluation and 2 blood samples each at screening and on Day 7 will be collected for pharmacodynamic evaluation. Participants will take part in the study for about 10 weeks.

Detailed description:
This is an interventional, Pharmacokinetic (PK), Pharmacodynamic (PD), phase 1, open label study in children 6 to less than 12 years of age with ≥50% scalp hair loss due to severe alopecia areata. The purpose of the study is to collect data to support dose selection for subsequent studies in the same population.

Participants will be screened and, if all eligibility criteria are met, will receive the first dose of Investigational product within 28 days after the screening visit.

Participants will receive 20 mg ritlecitinib in one dose, daily, for 7 consecutive days. Blood samples for pharmacodynamic evaluation will be collected on screening and Day 7. Blood samples for pharmacokinetic evaluation will be collected on Day 7 at: 0 hr (pre-dose), 0.5 hr, 1 hr, 3 hrs, and 8 hrs after dosing.

At least 12 evaluable participants with respect to the primary endpoint will be enrolled in the study.

Participants and their parents/legal guardians will be required to visit the study site 3 times during the study (Screening, Day 1 and Day 7) A safety follow-up visit will be conducted by phone, 28 to 35 days after the last dose of ritlecitinib.

Arms: arm 1: Participants will receive Ritlecitinib 20 mg by mouth once daily (QD).
Interventions: intervention 1: Ritlecitinib 20 mg
Intervention descriptions: intervention 1: orally administered, Ritlecitinib 20 mg once daily (QD)

Protocol documents:
Prot_000.pdf: 
Ritlecitinib (PF-06651600) 
Protocol B7981031 
Final Protocol, 03 Oct 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
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. 
 
 
AN INTERVENTIONAL PK, PD, PHASE 1, OPEN-LABEL STUDY TO 
INVESTIGATE PK AND PD OF MULTIPLE-DOSE RITLECITINIB IN CHILDREN 
6 TO LESS THAN 12 YEARS OF AGE WITH SEVERE ALOPECIA AREATA 
Study Intervention Number: 
PF-06651600 
Study Intervention Name: 
Ritlecitinib 
US IND Number: 
131503 
EudraCT/CTIS Number: 
NA 
ClinicalTrials.gov ID: 
NA 
Pediatric Investigational Plan Number: 
EMEA-002451-PIP01-18 
Protocol Number: 
B7981031 
Phase: 
1 
Brief Title: An Open-Label, Multiple-Dose, PK, PD Study of Ritlecitinib in Children 6 
to <12 Years of Age With Severe Alopecia Areata 
 


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Document History 
 
Document 
Version Date 
Original protocol 
03 Oct 2022 


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TABLE OF CONTENTS 
LIST OF TABLES ..................................................................................................................... 8 
LIST OF FIGURES .................................................................................................................... 8 
1. PROTOCOL SUMMARY ..................................................................................................... 9 
1.1. Synopsis ..................................................................................................................... 9 
1.2. Schema ..................................................................................................................... 16 
1.3. Schedule of Activities .............................................................................................. 17 
2. INTRODUCTION ................................................................................................................ 21 
2.1. Study Rationale ........................................................................................................ 21 
2.2. Background .............................................................................................................. 21 
2.2.1. Clinical Overview of Ritlecitinib ................................................................ 23 
2.2.1.1. Pharmacokinetic Overview of Ritlecitinib ................................ 23 
2.2.1.2. Safety of Ritlecitinib in Adult and Adolescent Participants 
With AA (Study B7931015) .............................................................. 23 
2.3. Benefit/Risk Assessment ......................................................................................... 25 
2.3.1. Risk Assessment ......................................................................................... 26 
2.3.2. Benefit Assessment ..................................................................................... 27 
2.3.3. Overall Benefit/Risk Conclusion ................................................................ 27 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................................ 27 
4. STUDY DESIGN ................................................................................................................. 27 
4.1. Overall Design ......................................................................................................... 27 
4.2. Scientific Rationale for Study Design ..................................................................... 28 
4.2.1. Patient Input Into Design ............................................................................ 28 
4.2.2. Diversity of Study Population ..................................................................... 29 
4.2.3. Adjudication Committee ............................................................................. 29 
4.2.4. E-DMC ........................................................................................................ 30 
4.2.5. Choice of Contraception/Barrier Requirements .......................................... 30 
4.3. Justification for Dose ............................................................................................... 30 
4.4. End of Study Definition ........................................................................................... 31 
5. STUDY POPULATION ...................................................................................................... 31 
5.1. Inclusion Criteria ..................................................................................................... 31 
5.2. Exclusion Criteria .................................................................................................... 33 


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5.3. Lifestyle Considerations ......................................................................................... 35 
5.3.1. Contraception ............................................................................................. 35 
5.3.2. Meals and Dietary Restrictions .................................................................. 36 
5.3.3. Caffeine, Alcohol, and Tobacco ................................................................. 36 
5.4. Screen Failures ........................................................................................................ 36 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................. 37 
6.1. Study Intervention(s) Administered ........................................................................ 37 
6.1.1. Administration ............................................................................................ 38 
6.2. Preparation, Handling, Storage, and Accountability .............................................. 38 
6.2.1. Preparation and Dispensing ........................................................................ 40 
6.3. Assignment to Study Intervention .......................................................................... 40 
6.4. Blinding .................................................................................................................. 40 
6.5. Study Intervention Compliance .............................................................................. 40 
6.5.1. Missed doses .............................................................................................. 41 
6.6. Dose Modification .................................................................................................. 41 
6.7. Continued Access to Study Intervention After the End of the Study ..................... 42 
6.8. Treatment of Overdose ........................................................................................... 42 
6.9. Prior and Concomitant Therapy .............................................................................. 42 
6.9.1. Prohibited Medications .............................................................................. 42 
6.9.2. Prohibited and Permitted Concomitant CYP3A Inducers, and 
CYP3A and CYP1A2 Substrates .................................................................... 43 
6.9.2.1. Prohibited Concomitant CYP3A Inducers and Substrates........ 43 
6.9.2.2. Permitted Concomitant CYP3A Substrates .............................. 44 
6.9.2.3. Prohibited Concomitant CYP1A2 Substrates ........................... 44 
6.9.2.4. Permitted Concomitant CYP1A2 Substrates ............................ 44 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................... 44 
7.1. Permanent Discontinuation of Study Intervention ................................................. 44 
7.1.1. Adverse Event ............................................................................................ 45 
7.1.2. Protocol Deviation ..................................................................................... 45 
7.1.3. Withdrawal of Consent .............................................................................. 45 
7.1.4. Pregnancy ................................................................................................... 46 
7.1.5. COVID-19 .................................................................................................. 46 


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7.1.6. Temporary Discontinuation ......................................................................... 46 
7.2. Participant Discontinuation/Withdrawal From the Study ....................................... 46 
7.2.1. Withdrawal of Consent ............................................................................... 47 
7.3. Lost to Follow-Up ................................................................................................... 47 
8. STUDY ASSESSMENTS AND PROCEDURES ............................................................... 48 
8.1. Administrative and Baseline Procedures ................................................................. 48 
8.1.1. Baseline Procedures .................................................................................... 49 
8.1.2. Telehealth Visits .......................................................................................... 49 
8.1.3. Home Health Visits ..................................................................................... 50 
8.2. Efficacy Assessments .............................................................................................. 50 
8.2.1. Rater Qualifications .................................................................................... 50 
8.3. Safety Assessments .................................................................................................. 51 
8.3.1. Physical Examinations ................................................................................ 51 
8.3.2. Vital Signs ................................................................................................... 52 
8.3.2.1. Blood Pressure and Heart Rate .................................................. 52 
8.3.3. Clinical Safety Laboratory Assessments ..................................................... 52 
8.3.3.1. Alternative Facilities for Clinical Safety Laboratory 
Assessment ......................................................................................... 53 
8.3.4. Pregnancy Testing ....................................................................................... 53 
8.3.5. Suicidal Ideation and Behavior Risk Monitoring ........................................ 54 
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................. 54 
8.4.1. Time Period and Frequency for Collecting AE and SAE Information........ 54 
8.4.1.1. Reporting SAEs to Pfizer Safety ............................................... 55 
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF ................... 55 
8.4.2. Method of Detecting AEs and SAEs ........................................................... 55 
8.4.3. Follow-Up of AEs and SAEs ...................................................................... 55 
8.4.4. Regulatory Reporting Requirements for SAEs ........................................... 56 
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure ..................................................... 56 
8.4.5.1. Exposure During Pregnancy ...................................................... 56 
8.4.5.2. Exposure During Breastfeeding ................................................. 58 
8.4.5.3. Occupational Exposure .............................................................. 59 
8.4.6. Cardiovascular and Death Events ................................................................ 59 


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8.4.7. Disease Related Events and/or Disease Related Outcomes Not 
Qualifying as AEs or SAEs ............................................................................. 59 
8.4.8. Adverse Events of Special Interest ............................................................. 59 
8.4.8.1. Lack of Efficacy ....................................................................... 59 
8.4.9. Medication Errors ....................................................................................... 59 
8.5. Pharmacokinetics .................................................................................................... 60 
8.6. Genetics .................................................................................................................. 62 
8.6.1. Specified Genetics ...................................................................................... 62 
8.7. Pharmacodynamics ................................................................................................. 62 
8.7.1. Biomarkers ................................................................................................. 62 
8.7.2. Samples for Interferon Gamma-Induced Protein 10 (IP-10) Analysis ....... 63 
8.7.3. Samples for Fluorescence-Activated Cell Sorting Analysis (T Cell, B 
Cell, and NK Cell Subsets) ............................................................................. 63 
8.7.4. Specified Gene Expression (RNA) Research ............................................ 63 
8.7.5. Specified Protein Research ......................................................................... 63 
8.7.6. Specified Metabolomic Research ............................................................... 63 
8.7.7. Retained Research Samples for Biomarkers .............................................. 63 
8.8. Immunogenicity Assessments ................................................................................ 63 
8.9. Health Economics ................................................................................................... 63 
9. STATISTICAL CONSIDERATIONS ................................................................................ 63 
9.1. Statistical Hypothesis ............................................................................................. 63 
9.2. Analysis Sets ........................................................................................................... 64 
9.3. Statistical Analyses ................................................................................................. 64 
9.3.1. Safety Analyses .......................................................................................... 64 
9.3.2. Pharmacokinetic Analyses ......................................................................... 64 
9.3.3. Pharmacodynamic Analyses ...................................................................... 65 
9.3.4. Taste Assessment Analyses ....................................................................... 65 
9.4. Interim Analyses ..................................................................................................... 65 
9.5. Sample Size Determination .................................................................................... 65 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.......................................................................................................... 66 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............... 66 
10.1.1. Regulatory and Ethical Considerations .................................................... 66 


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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................ 66 
10.1.2. Financial Disclosure ................................................................................. 67 
10.1.3. Informed Consent/Assent Process ........................................................... 67 
10.1.4. Data Protection ......................................................................................... 68 
10.1.5. Committees Structure ............................................................................... 69 
10.1.5.1. Data Monitoring Committee ................................................... 69 
10.1.6. Dissemination of Clinical Study Data ...................................................... 69 
10.1.7. Data Quality Assurance ............................................................................ 70 
10.1.8. Source Documents ................................................................................... 71 
10.1.9. Study and Site Start and Closure .............................................................. 72 
10.1.10. Sponsor’s Medically Qualified Individual ............................................. 73 
10.2. Appendix 2: Clinical Laboratory Tests ................................................................ 74 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ..................................................................... 75 
10.3.1. Definition of AE ....................................................................................... 75 
10.3.2. Definition of an SAE ................................................................................ 76 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ........................................................................... 77 
10.3.4. Reporting of SAEs ................................................................................... 81 
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................ 82 
10.4.1. Male Participant Reproductive Inclusion Criteria ................................... 82 
10.4.2. Female Participant Reproductive Inclusion Criteria ................................ 82 
10.4.3. Woman of Childbearing Potential ............................................................ 83 
10.4.4. Contraception Methods ............................................................................ 84 
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments ....... 86 
10.6. Appendix 6: Kidney Safety Monitoring Guidelines ............................................. 88 
10.6.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury ............................................................................. 88 
10.6.2. Age-Specific Kidney Function Calculation Recommendation ................ 88 
10.6.3. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities .................................................................................................. 88 
10.7. Appendix 7: Prohibited Concomitant Medications That May Result in DDI ....... 89 
10.8. Appendix 8: Country-Specific Requirements ........................................................ 91 


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10.8.1. France ........................................................................................................ 91 
10.8.2. Japan ......................................................................................................... 91 
10.8.2.1. Reporting Requirements .......................................................... 91 
10.8.2.2. Reporting Procedure ................................................................ 92 
10.9. Appendix 9: Hepatitis B testing algorithm and full eligibility criteria .................. 93 
10.10. Appendix 10 – SALT .......................................................................................... 94 
10.11. Appendix 11 – C-SSRS ....................................................................................... 95 
10.12. Appendix 12 – CDRS-R ...................................................................................... 96 
10.13. Appendix 13.1 – PROMIS® Parent Proxy Short Form v2.0 – Anxiety 8a .......... 97 
10.13.1. Appendix 13.2 – PROMIS® Parent Proxy Short Form v2.0 – 
Depressive Symptoms 6a ................................................................................. 97 
10.14. Appendix 14 - BRIEF®2 ..................................................................................... 98 
10.15. Appendix 15 - Modified CDLQI ......................................................................... 99 
10.16. Appendix 16 - WISC-V ..................................................................................... 100 
10.17. Appendix 17: Abbreviations .............................................................................. 101 
Hepatitis B Virus Deoxyribonucleic acid ............................................................ 102 
11. REFERENCES ................................................................................................................. 105 
 
LIST OF TABLES 
Table 1. 
Definitions of PK Parameters ................................................................... 64 
Table 2. 
Protocol-Required Safety Laboratory Assessments ................................. 74 
Table 3. 
Prohibited Concomitant CYP3A Inducers and Substrates ....................... 89 
Table 4. 
Prohibited Concomitant CYP1A2 Substrates .......................................... 90 
 
 
LIST OF FIGURES 
Figure 1. 
Study Visits and Procedures ...................................................................... 16 


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: An Interventional PK, PD, Phase 1, Open-Label Study to Investigate PK and 
PD of Multiple-Dose Ritlecitinib in Children 6 to less than 12 Years of Age With Severe 
Alopecia Areata 
Brief Title: An Open-Label, Multiple-Dose, PK, PD Study of Ritlecitinib in Children 6 to 
<12 Years of Age With Severe Alopecia Areata 
Regulatory Agency Identification Number(s): 
 
US IND Number: 
131503 
EudraCT/CTIS Number: 
NA 
ClinicalTrials.gov ID: 
NA 
Pediatric Investigational Plan Number: 
EMEA-002451-PIP01-18 
Protocol Number: 
B7981031 
Phase: 
Phase 1 
 
Rationale: 
The PK assessments from this study are necessary to support ritlecitinib dose selection in 
subsequent studies in children aged 6 to <12 years of age. 
Objectives, Endpoints, and Estimands: 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To characterize the PK of ritlecitinib in children with 
AA 6 to <12 years of age. 
• 
AUC24 on Day 7 
Secondary: 
Secondary: 
• 
To further characterize the PK of ritlecitinib in children 
with AA 6 to <12 years of age. 
• 
Cmax, Tmax, CL/F, VZ/F and t½ on Day 7 
• 
To characterize the PD of ritlecitinib in children with 
AA 6 to <12 years of age. 
• 
Change from baseline in interferon gamma IP-10 and 
lymphocyte subsets (T cell, B cell, and NK cells) on 
Day 7 
• 
To evaluate the safety and tolerability of ritlecitinib in 
children with AA 6 to <12 years of age. 
• Treatment-emergent adverse events (AEs). 
• Treatment related AEs. 
• SAEs and AEs leading to discontinuation. 
• Clinically significant abnormalities in vital signs. 
• Clinically significant abnormalities in clinical laboratory 
values. 
• 
To assess the overall palatability, acceptability, and 
tolerability of the proposed age appropriate 
formulation in children with AA aged 6 to <12 years of 
age. 
• 
Taste assessment 


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Overall Design: 
Study B7981031 is a single-group, uncontrolled, open-label, interventional PK, PD study to 
estimate the systemic exposures of 20 mg QD of ritlecitinib in at least 12 children with AA, 6 
to <12 years of age, including at least 4 participants 6 to <9 years of age. 
The dose to be studied was derived by allometric scaling of results obtained from adults and 
adolescents who received ritlecitinib. Participants in this study will receive ritlecitinib for 
7 days, with PK, PD assessments on Day 7. 
Number of Participants: 
Twelve evaluable participants will be required to complete the PK analysis at Day 7. At 
sponsor’s discretion, up to 3 participants may be replaced if they do not provide a full set of 
evaluable PK data. 
Note: "Enrolled" means an agreement has been obtained of a participant and their legally 
authorized representative(s)to participate in a clinical study following completion of the 
informed consent process and assignment to study intervention. A participant will be 
considered enrolled if the informed consent is not withdrawn prior to participating in any 
study activity. Potential participants who are screened for the purpose of determining 
eligibility for the study, but do not participate in the study, are not considered enrolled. 
Study Population: 
The full set of inclusion/exclusion criteria is provided in Section 5 of the protocol. 
Key inclusion and exclusion criteria are listed below: 
Key Inclusion Criteria 
Participants must meet the following key inclusion criteria to be eligible for enrollment into 
the study: 
1. 
Children who are 6 to <12 years old at the time of the screening visit. Refer to 
(Section 10.4) for reproductive criteria for male and female participants. 
2. 
A diagnosis of severe AA, including AT and AU, with ≥50% scalp hair loss due to AA 
(ie, a SALT score ≥50) at both the Screening and Baseline visits, without evidence of 
terminal hair regrowth within the previous 12 months. 
3. 
For study participants in the EU/UK only: 
History of clinical response failure to AA treatment (such as topical, off-label 
pharmacologic, or hairpiece prosthetics) 


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AND EITHER: 
a. Participants with a history of psychological counseling for AA (as evidenced by 
Screening AA assessments) in the past year prior to Screening 
Participants are eligible if current psychosocial impairment is confirmed by 
administering all four instruments listed below and meeting the specified thresholds: 
• PROMIS® Parent Proxy Anxiety Symptoms: T-score 60-70 
• PROMIS® Parent Proxy Depressive Symptoms: T-score 60-70 
• BRIEF®2 (BRI, ERI, CRI): T-score 60-70 on any one of the 3 components of the 
BRIEF®2. 
• Modified CDLQI (score of >7) 
OR 
b. Participants with no history of psychological counseling for AA in the past year prior 
to Screening 
In order to be eligible for this study, participants must: 
• Have a T-score of 60-70 on any one of the 3 instruments (PROMIS®Anxiety 
Symptoms or PROMIS®-Depressive Symptoms or any one of the 3 components 
of BRIEF®2) 
• Complete at least 5 psychological counseling sessions for AA prior to Screening 
• Be re-evaluated after completion of the psychological counseling and have a 
T-score of 60-70 on any one of the three instruments 
(PROMIS®Anxiety- Symptoms or PROMIS®-Depressive Symptoms or any one 
of the 3 components of BRIEF®2) 
Key Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded: 
1. 
Conditions that may impact absorption or metabolism of IP (eg, celiac disease, 
cholecystectomy or gastrectomy). 
2. 
History (one or more episodes) of CMV, varicella, herpes zoster (shingles) or 
disseminated herpes simplex. A history of uncomplicated herpes simplex is not 
exclusionary. 


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3. 
Other medical or psychiatric condition (including recent [within the past year] or active 
suicidal ideation/behavior) that may increase the risk of study participation or, in the 
investigator’s judgment, make the participant inappropriate for the study, including but 
not limited to: 
• For participants in the EU/UK with scores of >70 on the PROMIS® or any 
component of the BRIEF®2, or with previous history of suicidal behaviors in the past 
5 years, “Yes” answer for events that occurred in the past 5 years to any of the 
suicidal behavior items of the C-SSRS or with any lifetime history of serious or 
recurrent suicidal behavior, a risk assessment must be performed and documented by 
a qualified mental health professional to assess whether it is safe to participate in the 
trial. 
• For participants in the US and other non-EU/UK countries with a previous history of 
suicidal behaviors in the past 5 years, “Yes” answer for events that occurred in the 
past 5 years to any of the suicidal behavior items of the C-SSRS or with any lifetime 
history of serious or recurrent suicidal behavior, a risk assessment must be performed 
and documented by a qualified mental health professional to assess whether it is safe 
to participate in the trial. 
• For participants in the US and other non-EU/UK countries: Clinically significant 
depression per the CDRS-R (T-score ≥40). 
• History of or presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 
4. 
Renal dysfunction defined as: 
• eCrCl normalized to BSA: confirmed eCrCl <60 mL/min/1.73 m2 based on 
Modified Schwartz equation (pediatric patients 2 to <12 years of age). See 
Appendix 6. 
5. 
Hepatic dysfunction defined as: 
• Total bilirubin >1.5 × ULN (except for Gilbert’s syndrome) 
• AST >1.5 × ULN 
• ALT >1.5 × ULN 
6. 
Hematologic abnormalities defined as: 
• Absolute neutrophil count <1.2 × 109/L (<1200/mm3) 
• Hemoglobin <11.0 g/dL 
• 
Platelet count <150 × 109/L (<150,000/mm3) 


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• Absolute lymphocyte count of <0.8 ×109 /L (<800/mm3) 
7. 
Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members. 
Study Arms and Duration: 
The study includes a screening period of up to 28 days, a 7-day interventional period, and a 
28 day follow-up period. The duration of study participation for each participant is 
approximately 9 weeks. 
 
Study Intervention(s) 
Intervention Name 
Ritlecitinib (PF-06651600) 
Arm Name 
(group of participants receiving a specific 
treatment or no treatment) 
Active study medication 
Unit Dose Strength(s) 
20 mg 
Route of Administration 
Oral 
Use 
Experimental 
IMP or NIMP/AxMP 
IMP 
 
 
Arm Title 
experimental 
Arm Type 
experimental 
Arm Description 
Participants will receive 
study medication, 20 mg 
per day, for 7 days. 
 
Statistical Methods: 
A sample size of 12 participants should provide adequate pharmacokinetic information. The 
plasma PK parameters will be listed and summarized descriptively. Plasma concentrations 
will be listed and summarized descriptively by nominal PK sampling time. Individual 
participant and median profiles of the plasma concentration-time data will be plotted using 
actual and nominal times, respectively. Median profiles will be presented on both linear- 
linear and log-linear scales. 
Taste acceptability assessment questionnaire will be included. Taste acceptability will be 
listed and summarized descriptively (frequencies and percentages). 


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Ethical Considerations: 
As of August 2022, there are no systemic treatments approved by Health Authorities for the 
treatment of AA in pediatric patients. 
Review of the treatment guidelines and recommendations indicates that a number of off-label 
therapies are frequently used after assessing factors such as the age of the patient, disease 
extent and disease duration. However, there is neither a cure for AA nor is there a therapy 
convincingly demonstrated to induce and sustain drug-free remission long term. 1,2,3,4,5 Most 
recently, JAK inhibitors have been studied in AA and encouraging reports regarding their 
efficacy have been published and presented. 6,7,8 
The results of previous studies of ritlecitinib in adults and adolescents support the 
investigation of ritlecitinib for AA in children and there is a favorable benefit-risk profile to 
support the rationale for this study. Taking into account the measures to minimize risk to 
participants, the potential risks associated with ritlecitinib are justified by the anticipated 
benefits of informing dose selection in studies evaluating ritlecitinib for the treatment of AA 
in children. 
This is a short-term PK, PD study and therefore no benefit to the participants is expected. 
However, participants who complete this study will qualify to be screened for a planned 
long-term, open-label study, where ritlecitinib (active dose only) will be provided for up to 
3 years. Dose selection for this planned study will be based on results from Study B7981031, 
and thus enrollment into the planned long-term study will not occur immediately after Study 
B7981031. 
The clinical data from the B7981015 study of ritlecitinib in adults and adolescents (≥ 12 to 
<18 years of age) with AA indicate that ritlecitinib has a favorable benefit/risk profile for 
treatment of adults and adolescents with AA for up to 48 weeks. It provides meaningful 
clinical benefit in this serious disease with no approved treatment options in pediatric 
populations, and it has an acceptable safety profile. The benefit of evaluating ritlecitinib in 
children is additionally supported by the prevalence of AA in children and the significant 
psychological burden of AA in this population. 
Participants and their parents/legal guardians will be expected to commit time for 
participating in this study as they will be required to visit the study site 3 times during the 
study (Screening, Day 1 and Day 7). Day 7 PK assessments will occur over an 8-hour period. 
Also, participants may experience some discomfort while undergoing study assessments such 
as blood draws. 


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Blood samples will be collected at Screening and Day 7 as follows: 
 
Study Visit 
Test 
Screening 
EOT 
Screening 
Hematology 
0.5 ml 
0.5 ml 
Blood chemistry 
0.5 ml 
0.5 ml 
QFT 
1 ml 
IP-10 
1 ml 
1 ml 
Lymphocyte subsets 
2 ml 
2 ml 
Hepatitis B/C 
2 ml 
HIV 
2 ml 
Pregnancy (serum) 
2 ml 
Day 7 
PK 
5 ml (5 × 1 ml) 
Total Blood Volume 
11 ml 
9 ml 
 
Additional blood tests may be required for safety reasons, as determined by the Investigator. 
The total amount of blood must be within the allowed limits for this patient population (see 
Section 8.1 for details). 
In addition, participants must agree to use appropriate contraception methods if applicable, 
not use prohibited medications, and to follow protocol specified lifestyle guidelines during 
the study (see Appendix 4 and Appendix 7 for details). 
The study incorporates mitigations against known risks to ensure the safety of the trial 
participants. 


Ritlecitinib (PF-06651600) 
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Page 16 
 
 
 Final Protocol, 03 Oct 2022 
 
 
1.2. Schema 
Figure 1. 
Study Visits and Procedures 
 
28-35 Days 
28 
Safety 
Days 
Follow-up 
Screening 
e, 
- 
t 
Beginning of Treatment 
End of Treatment 
End of 
Study 
 
Visit Types: 
• 
Treatment) or Early Tennination 
 
• 
Telephone visits: Days 2, 4, 6 and End of Study 
 
• 
 
 
• 
 
 
 
 
 
Office visits: Screening, Day 1 (Beginning of treatment), Day 7 (End of 
e, 
e, 
e, 
e, 
e, e,
N 
w 
VI 
0\ 
--.)


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Protocol B7981031 
Final Protocol, 03 Oct 2022 
PFIZER CONFIDENTIAL 
Page 17 
 
 
 
1.3. Schedule of Activities 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed infonnation 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 paiiicipant. These visits may be conducted in the clinic, by telephone, or in the 
paiiicipant's home. 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Aooendix 17 
Sc1·een 
T1·eatment Period 
F/U 
End of Study 
Notes 
Up to 28 
days 
before 
Day 1 
Day 
1 
Base
line 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day7 
EOT 
Day 35 to 42 • Day relative to strut of study intervention (Day 1). 
• F/U contact may occur via telephone and must occur 28 to 35 days after 
administration of the final dose of study intervention. 
• If treatment is discontinued prior to Day 7, an EOT visit must be conducted, 
followed by an End of Study visit at 28-35 days after the last dose. 
• If paiticipation in the study and treatment ai·e discontinued at the saine time, 
the EOT and EOS visits will be conducted together. 
• All screening should be done <28 davs before the first dose. 
In-office visits 
X 
X 
X 
• In addition to specified in-office and telephone visits, additional in-office, 
telephone or in-home visits may be conducted at any time during the study 
for safety reasons or for reasons related to dosing or PK, PD blood draws. 
Telephone visits 
X 
X 
X 
X 
Informed 
consent/assent 
X 
• Infonned consent and pa1ticipant assent should be obtained prior to 
undergoing any study-specific procedures. 
Screen for 
inclusion/exclusion 
criteria 
X 
Demographics 
X 
Registration/ 
drug assiIDunent 
X 
At registration, the pa1ticipant enrollment number and treatment allocation are 
assiQtled. 
Medical Histon and Phvsical Examination 
Medical history 
X 
Full physical 
examination 
X 


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PFIZER CONFIDENTIAL 
Page 18 
 
 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Annendix 17 
Screen 
T1·eatment Period 
F/U 
End of Study 
Notes 
Up to 28 
days 
before 
Day 1 
Day 
1 
Base
line 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day7 
EOT 
Day 35 to 42 • Day relative to strut of study intervention (Day 1). 
• F/U contact may occur via telephone and must occur 28 to 35 days after 
administration of the final dose of study intervention. 
• If treatment is discontinued prior to Day 7, an EOT visit must be conducted, 
followed by an End of Study visit at 28-35 days after the last dose. 
• If paiticipation in the study and treatment ai·e discontinued at the saine time, 
the EOT and EOS visits will be conducted together. 
• All screening should be done <28 days before the first dose. 
Brief physical 
examination 
X 
X 
Weillht/Heillht 
X 
Vital siQtls 
X 
X 
heart rate, blood pressure 
Contraception check (if 
aoolicable) 
X 
X 
X 
Laborntory Assessments 
Hematolo2v 
X 
X 
Blood chemistry 
X 
X 
QFT , Hepatitis B and 
C,HIV 
X 
Urine dipstick 
X 
Urinalysis will be perfonned by dipstick in the clinic and the result documented 
at the site level (source document) ; if an abnonnal or symptomatic result is 
observed, the sample will be sent to the local laboratory. Microscopic analysis 
and urine culture will be performed if suspicion ofUTI and urinalysis is 
!Positive for nitrite and/or leukocyte esterase or if otherv.•ise clinically indicated. 
Pregnancy test 
X 
X 
X 
Required only in females of childbearing potential. Semm at screening, urine at 
baseline and EOT. 
See Section 8.3.4 for additional info1mation) 
Study Inte1-vention and Other Treatments 
Study medication 
intervention 
administration 
X 
X 
X 
X 
X 
X 
X 
Prior/concomitant 
treatment(s) 
X 
X 
X 
X 
X 
X 
X 


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Page 19 
 
 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Annendix 17 
Screen 
T1·eatment Period 
F/U 
End of Study 
Notes 
Up to 28 
days 
before 
Day 1 
Day 
1 
Base
line 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day7 
EOT 
Day 35 to 42 • Day relative to strut of study intervention (Day 1). 
• F/U contact may occm via telephone and must occur 28 to 35 days after 
administration of the final dose of study intervention. 
• If treatment is discontinued prior to Day 7, an EOT visit must be conducted, 
followed by an End of Study visit at 28-35 days after the last dose. 
• If paiticipation in the study and treatment ai·e discontinued at the saine time, 
the EOT and EOS visits will be conducted together. 
• All screening should be done <28 days before the first dose. 
Assessments 
SALT score 
X 
X 
Taste Assessment 
Questionnaire 
X 
Serious and nonserious 
AE monitoring 
X 
X 
X 
X 
X 
X 
X 
C-SSRS suicidal 
ideation and behavior 
risk assessment 
X 
CDRS-R 
X 
US and other non-EU/UK countries 
PROMIS® Pai·ent 
Proxy 
X 
EU/UK only 
BRIEF®2 (BRI, ERi, 
CRI) 
X 
EU/UK only 
Modified CDLOI 
X 
EU/UKonlv 
WISC-V (Wechsler 
Intelligence Scale for 
Children - 5th edition) 
X 
EU/UK only 
Documentation of 
psychological 
counseling 
X 
EU/UK only 
Phannacokinetic Assessments 
See laboratory manual. 


Ritlecitinib (PF-06651600) 
Protocol B7981031 
Final Protocol, 03 Oct 2022 
Page 20 
 
 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Annendix I7 
Screen 
T1·eatment Period 
F/U 
End of Study 
Notes 
Up to 28 
days 
before 
Day 1 
Day 
1 
Base
line 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day7 
EOT
Day 35 to 42 • Day relative to strut of study intervention (Day 1). 
• F/U contact may occm via telephone and must occur 28 to 35 days after 
administration of the final dose of study intervention. 
• If treatment is discontinued prior to Day 7, an EOT visit must be conducted, 
followed by an End of Study visit at 28-35 days after the last dose. 
• If paiticipation in the study and treatment ai·e discontinued at the saine time, 
the EOT and EOS visits will be conducted together. 
• All screening should be done <28 davs before the first dose. 
PK samples 
X 
• PK samples required at Day 7 at Ohr (pre-dose), and 0.5 hr, 1 hr, 3 hrs, and 
8 hrs after dosing. 
• PK will be conducted only on Day 7 and only if no more than one dose was 
missed between Davs 2 and 5. 
• 
Phannacodvnamic assessments 
IP-10 
X 
X 
• To be collected before dose. 
• IP-10 will be collected at screening and Day 7 only. If treatment is 
discontinued, IP-10 will not be collected on Dav 7. 
Lymphocyte subsets (T 
cells, B cells, and NK 
cells) 
X 
X 
• Lymphocyte subsets will be collected at screening and Day 7 only. If 
treatment is discontinued, lymphocyte subsets will not be collected at Day 7. 


Ritlecitinib (PF-06651600) 
Protocol B7981031 
Final Protocol, 03 Oct 2022 
PFIZER CONFIDENTIAL 
Page 21 
 
 
2. INTRODUCTION 
2.1. Study Rationale 
The PK and PD assessments from this study are necessary to support ritlecitinib dose 
selection in subsequent studies in children 6 to <12 years of age. 
2.2. Background 
AA is a chronic relapsing T-cell mediated autoimmune disorder characterized by non- 
scarring hair loss affecting children and adults across all ages, races, and sexes.9,10 AA is 
associated with other immune diseases including asthma, allergic rhinitis, atopic dermatitis, 
and autoimmune diseases such as thyroiditis and vitiligo.10 
 
CD8+ T cells, NK cells, and mast cells are involved in the pathogenesis of AA. The possible 
inflammatory pathways in AA include cytokines from the TH1 axis, including IFN α, IFN γ, 
and IFNγ -IP-10.11,12 Mouse models have shown that IL-2 and IL-15 play a role in the 
initiation of auto-reactive CD8+ cells that attack hair follicles.13 IL-12 and IL-23 may also 
play a role in the pathogenesis of AA. 
Clinical presentation of AA can be limited to small, circular patches of scalp hair loss (patchy 
hair loss, alopecia focalis), involve complete loss of hair on the scalp (AT), or total loss of 
hair on the scalp and body (AU). AA involving 50% or greater scalp hair loss, including AT 
and AU, is considered an advanced form of alopecia, according to the US National Alopecia 
Areata Foundation.14 Patchy alopecia is the most common form of AA which may develop 
into the more extensive and often treatment-resistant forms of AA, especially with earlier age 
of onset.15 It is estimated that AA affects as many as 6 to 7 million individuals in the US10 
and 147 million worldwide.14 
 
The spontaneous remission rates for AA patients presenting with <50% scalp hair loss 
(patchy hair loss, alopecia focalis) are 30-50% within the first 6-12 months of disease onset, 
and 66% of the patients will show complete regrowth of hair within 5 years.16 The likelihood 
of complete regrowth spontaneously with AT or AU is less than 10%.17 
 
Further, there is evidence that AA can become refractory to JAK inhibition if it has been 
present for a substantial period of time. Specifically, a recent case series demonstrated that 
AA patients whose current episode of alopecia totalis or alopecia universalis had lasted more 
than 10 years were highly non-responsive to off-label tofacitinib treatment in comparison 
with patients with shorter duration.8 
Depression, anxiety, and panic disorders are often observed in patients with AA and the 
coping mechanisms of AA patients mirror those of grief and bereavement.18,19 A substantial 
body of evidence demonstrates a widespread impact of AA on the psychological health of 
both adult and pediatric patients with AA, including impairment in self-esteem, increased 
incidence of anxiety and depressive disorders and other psychological conditions,20,21,22,23,24 
problems with social relations,25 decreased HRQoL and QoL, as well as the QoL of their 
families.26,27,28,29,30,31,32,33,34 


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AA is a disease with significant pediatric prevalence, in addition to the burden of disease 
seen in adults, and ample evidence is available on the impact of AA on the mental health of 
adolescent patients. In a US study, children with AA had more psychological problems than 
those without AA. Specifically, those with AA exhibited more anxiety, depression, 
tendencies to withdraw, aggression, and delinquency. In addition, children with AA were 
more likely to exhibit somatic problems as well as problems in social relations and in 
attention span. Girls with AA seem to have been affected more in dimensions of total 
problems, anxiety/depression, and internalizing/externalizing syndromes. Children with AA 
were also less likely to have experienced positive life events in the year prior to exhibiting 
AA signs.25 
In addition to experiencing a significant mental health burden, children with AA report 
experiencing other negative impacts to their QoL. Specifically, 75% of children aged 15-19 
years reported instances of effects on QoL, 50% reported that the disease limited their 
participation in activities, 40% reported instances of bullying, and 35% reported that others 
noticed and commented on their condition. Rates of decrement in QoL, limitations on 
participation in activities, and bullying were heightened in older children aged 15-19 years 
compared to younger children.35 
Given the finding that complete scalp hair loss with duration >10 years in adults is less likely 
to respond to treatment, pursuing treatment, even if only intermittently, in adolescents or 
even younger patients with stable, severe AA may prevent future irreversible hair loss.8 
Additionally, an earlier age of first onset has been reported to correspond to an increased 
lifetime risk of extensive disease. Differences in treatment responses are not expected for 
adolescent versus adult AA patients as suggested in 2 reports of tofacitinib (off-label use). 8,36 
No meaningful differences were observed between treatment responses in adults and 
adolescents treated with ritlecitinib in Study B7981015 (reference Pfizer data on file). 
As of August 2022, there are no systemic treatments approved by Health Authorities for the 
treatment of AA in pediatric patients. 
Review of the treatment guidelines and recommendations indicates that a number of off-label 
therapies are frequently used after assessing factors such as the age of the patient, disease 
extent, and disease duration. However, there is neither a cure for AA, nor is there a therapy 
convincingly demonstrated to induce and sustain drug-free remission long term.1-5 
Previous studies (B7981015 and B7981032) included adult and pediatric populations 
between ages of 12 to <18 years. 
This study is specifically designed to collect data supporting a dose selection for pediatric 
patients 6 to <12 years of age. 


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PFIZER CONFIDENTIAL 
Page 23 
 
 
2.2.1. Clinical Overview of Ritlecitinib 
 
The ritlecitinib AA clinical development program was designed to evaluate the efficacy and 
safety of ritlecitinib treatment in adolescent (12 to <18 years of age) and adult (≥18 years of 
age) AA patients with ≥50% scalp hair loss (as assessed by SALT), including AT and AU. 
 
The clinical development program of ritlecitinib in AA was a global program including 21 
Phase 1 studies, 4 Phase 2/3 studies in AA and 1 Phase 2b study in vitiligo. The study in 
vitiligo is relevant for the evaluation of safety in AA due to similarities between the AA and 
vitiligo populations (including disease pathophysiology, age distribution, comorbidities), 
similar ritlecitinib dosing regimens to those in the AA studies, and similar safety monitoring 
in vitiligo and AA study protocols. 
 
As of 30 May 2022, ritlecitinib had been orally administered to 1630 participants in these 5 
Phase 2/3 clinical efficacy and safety studies, as follows: B7931005 (Phase 2a in AA), 
B7981015 (Phase 2b/3 in AA), B7981037 (Phase 2a AA study to provide additional data 
regarding the clinical relevance of the axonal dystrophy finding in the 9-month dog toxicity 
study), B7981032 (Phase 3 long-term safety study in AA), and B7981019 in vitiligo. 
 
2.2.1.1. Pharmacokinetic Overview of Ritlecitinib 
 
The PK profile of ritlecitinib is characterized by rapid absorption, rapid elimination (t½ of 
~2 hours) and is approximately dose proportional. Steady state generally appears to have 
been reached by Day 4 for the QD regimens and Day 6 for the BID regimens based on 
similar median trough (pre-dose) ritlecitinib beyond Day 6. Ritlecitinib has been evaluated at 
single oral doses ranging from 5 mg to 800 mg and multiple oral doses ranging from 50 mg 
to 400 mg QD and at 100 mg and 200 mg BID for 14 days. The clearance mechanisms for 
ritlecitinib in humans appear to be primarily by metabolism. Less than 10% of ritlecitinib is 
excreted unchanged in the urine. 
 
2.2.1.2. Safety of Ritlecitinib in Adult and Adolescent Participants With AA (Study 
B7931015) 
 
B7981015 was a Phase 2b/3, randomized, double blind, placebo controlled, dose ranging 
study to investigate ritlecitinib in both adolescent (≥12 to <18 years old) and adult (≥18 years 
old) participants with ≥50% scalp hair loss due to AA. The study had a maximum duration of 
approximately 57 weeks. This included an up to 5-week Screening period, a 48-week 
treatment period, and a 4-week follow up period. The treatment period was comprised of a 
placebo-controlled period that included a 4-week loading phase and a 20-week maintenance 
phase, followed by a 24-week extension phase. 
 
Eligible participants were randomized to blinded ritlecitinib and matching placebo in a 
2:2:2:2:1:1:1 (200 mg/50 mg, 200 mg/30 mg, 50 mg, 30 mg, 10 mg, placebo-200 mg/50 mg, 
and placebo-50 mg, respectively) manner for a total of 7 treatment sequences. 


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Protocol B7981031 
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PFIZER CONFIDENTIAL 
Page 24 
 
 
The study randomized 105 adolescents (12 to 17 years of age) and the distribution of 
adolescents across treatment groups was similar. 
 
Ritlecitinib 200/50 mg, 200/30 mg, 50 mg and 30 mg were significantly superior to placebo 
at Week 24 on clinician-assessed and patient-reported endpoints related to scalp hair 
regrowth (including response based on absolute SALT ≤20, response based on absolute 
SALT ≤10, and PGI-C response). Exposure response modelling based on SALT ≤20 and 
SALT ≤10 response at Week 24 showed a positive relationship between dose and response. 
Ritlecitinib 200/50 mg, 200/30 mg, 50 mg and 30 mg were also nominally superior to 
placebo at Week 24 in producing improvement in eyebrows and eyelashes. Continued 
improvement in efficacy endpoints was seen between Week 24 and Week 48. 
 
Overall efficacy was similar in adolescents (12 to <18 years of age) and adults (≥18 years of 
age). 
 
The proportion of participants who experienced all-causality TEAEs was similar across 
treatment groups up to Week 24 (placebo-controlled period) and up to Week 48 (overall). 
The most frequently reported TEAEs in any group included nasopharyngitis, headache, and 
upper respiratory tract infection. Up to week 24, the incidence of nasopharyngitis, folliculitis, 
urticaria, dizziness, upper respiratory tract infection and urinary tract infection was higher in 
participants treated with ritlecitinib (particularly 200/50 mg and 200/30 mg) than placebo. 
Most TEAEs were mild to moderate in severity. Fourteen participants experienced 16 SAEs 
up to Week 48: 
 
• 200/50 mg (4 participants): appendicitis; empyema and sepsis; invasive lobular breast 
carcinoma, spontaneous abortion. 
• 200/30 mg (2 participants): appendicitis; chemical poisoning and suicidal behavior. 
• 50 mg (2 participants): breast cancer; pulmonary embolism. 
• 30 mg (1 participant): diverticulitis. 
• 10 mg (2 participants): suicidal behavior; eczema. 
• Placebo-200/50 mg: no SAEs. 
• Placebo-50 mg (3 participants): spontaneous abortion; conversion disorder; heavy 
menstrual bleeding. These treatment-emergent SAEs were all reported during the 
Placebo-Controlled Period. 
 
Of the 16 SAEs, 12 were considered by the investigator as unrelated to study intervention. 
The 4 SAEs that were considered related to study intervention in the opinion of the 
investigator were sepsis and empyema (both in 1 participant); breast cancer; and eczema. 
There were no deaths in the study. 


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Protocol B7981031 
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PFIZER CONFIDENTIAL 
Page 25 
 
 
Treatment with ritlecitinib was associated with changes in hematological parameters, some of 
which were dose dependent. In the first weeks of the study, there were slight, transient 
decreases in hemoglobin and small, variable changes in neutrophil and leukocyte levels. 
Small, early decreases in platelets were observed with ritlecitinib treatment; these levels 
remained stable up to Week 48. Dose-dependent early decreases in absolute lymphocyte 
levels, CD3 (T lymphocytes) and T lymphocyte subsets (CD4 and CD8) were observed. 
There was a dose-dependent early decrease in CD16/56 (NK cells), particularly in groups 
who had received a 200 mg loading dose of PF‑06651600 for 4 weeks. Overall, there were no 
clinically meaningful effects of ritlecitinib on ALT, AST, bilirubin, or alkaline phosphatase. 
The incidence of elevation in hepatic enzymes was low and not dose dependent. Up to 
Week 48, there were no potential Hy’s law cases. 
 
Overall, ritlecitinib was safe and well-tolerated in the adolescent population. In general, there 
was a lower proportion of adolescent participants with SAEs, severe AEs and AEs of interest 
relative to adult (≥18 years of age) participants. The TEAEs suggest there are no risks unique 
to adolescents, except for a higher frequency of acne in the adolescent patients which is not 
unexpected considering that acne is generally more common in adolescents than adults. 
 
For a complete description and results of this study, please refer to the current version of the 
ritlecitinib IB. 
 
2.3. Benefit/Risk Assessment 
 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of ritlecitinib may be found in the current version of the IB, which is 
the SRSD for this study. 


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Protocol B7981031 
Final Protocol, 03 Oct 2022 
PFIZER CONFIDENTIAL 
Page 26 
 
 
2.3.1. Risk Assessment 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Study Intervention(s) Ritlecitinib 
• viral reactivation 
• serious infections and 
opportunistic infections 
• malignancy and 
lymphoproliferative disorders 
• thromboembolism 
• dermatologic effects (eg. rash, 
acne, folliculitis, urticaria) 
• reduction in platelet count and 
lymphocyte count 
Clinical experience with other 
JAK inhibitors 
Ritlecitinib clinical studies 
(B7931005, B7981015, 
B7981019, B7981032, and 
B7981037) and pre-clinical 
studies 
Exclusion of participants at risk 
Short duration of treatment 
Safety labs at screening, baseline and 
EOT Visit 
Study Procedures blood collection for PK 
Extravasation, bruising, local 
discomfort 
Collection of 5 PK samples on 
Day 7 
Use of highly qualified pediatric nurses, 
with venipuncture experience. 
When possible, use of IV canula, allowing 
all 5 samples to be collected with just one 
venipuncture. 


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PFIZER CONFIDENTIAL 
Page 27 
 
 
2.3.2. Benefit Assessment 
No immediate therapeutic benefits are expected from participation in this study. However, 
after completion of this study, participants will qualify to be screened for the planned 3-year, 
long-term, open-label (active dose only) Study B7981028. Dose selection for this planned 
study will be based on results from Study B7981031, and thus enrollment into the planned 
long-term study will not occur immediately after Study B7981031. Also, data collected in 
this study will support dose selection for the planned pediatric safety and efficacy Study 
B7981027. 
2.3.3. Overall Benefit/Risk Conclusion 
Taking into account the short treatment duration and the measures to minimize the risk to 
study participants (through the inclusion/exclusion criteria and safety monitoring), the 
potential risks identified in association with ritlecitinib are expected to be minimal and 
justified by the anticipated benefits of informing dose selection in studies evaluating 
ritlecitinib for the treatment of AA in children. 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To characterize the PK of ritlecitinib in children with 
AA 6 to <12 years of age. 
• 
AUC24 on Day 7 
Secondary: 
Secondary: 
• 
To further characterize the PK of ritlecitinib in children 
with AA 6 to <12 years of age. 
• 
Cmax, Tmax, CL/F, VZ/F and t½ on Day 7 
• 
To characterize the PD of ritlecitinib in children with 
AA 6 to <12 years of age. 
• 
Change from baseline in interferon gamma IP-10 and 
lymphocyte subsets (T cell, B cell, and NK cells) on 
Day 7 
• 
To evaluate the safety and tolerability of ritlecitinib in 
children with AA 6 to <12 years of age. 
• TEAE 
• Treatment related AEs. 
• Serious AEs (SAEs) and AEs leading to discontinuation. 
• Clinically significant abnormalities in vital signs. 
• Clinically significant abnormalities in clinical laboratory 
values. 
• 
To assess the overall palatability, acceptability, and 
tolerability of the proposed age appropriate 
formulation in children with AA aged 6 to <12 years of 
age. 
• 
Taste assessment 
 
4. STUDY DESIGN 
4.1. Overall Design 
This is an interventional, PK, PD, Phase 1, open label study in children 6 to less than 12 
years of age with ≥50% scalp hair loss due to AA. The purpose of the study is to collect data 
to support dose selection for subsequent studies in the same population. 
Participants will be screened and, if all eligibility criteria are met, will receive the first dose 
of IP within 28 days after the screening visit. 


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Participants will receive 20 mg ritlecitinib in one dose, daily, for 7 consecutive days. On 
Day 7 (EOT) blood samples for PK will be collected at: 
• 0 hr (pre-dose) 
• 0.5 hr, 
• 1 hr, 
• 3 hrs, and 
• 8 hrs after dosing. 
At least 12 evaluable participants with respect to the primary endpoint will be enrolled in the 
study. Participants that are not able to provide a full set of evaluable PK data or that miss 
more than one dose may be replaced at the discretion of the sponsor. 
A follow-up visit will be conducted by phone, 28 to 35 days after the last dose of ritlecitinib. 
4.2. Scientific Rationale for Study Design 
The PK assessments from this study are necessary to support ritlecitinib dose selection in 
subsequent studies in children 6 to <12 years of age. The systemic exposure assessments 
from this study will provide information on whether the selected dose for children 6 to 
<12 years old provides exposures similar to the proposed dose for adolescents and adults. 
The PD endpoints of IP-10 and lymphocyte subsets will be assessed to understand if there is 
any difference in PD responses between children 6 to less than 12 years of age, and adults 
and adolescents. The open-label, 7-day study design has been reviewed by the US FDA and 
the EMA and agreed as part of the iPSP and PIP, respectively. 
The 20 mg dose selected is predicted to provide exposures in 6 to <12 year old children, 
similar to the 30 mg dose in adults and adolescents. 
 
The study is designed as a 7 day multiple dose study. Multiple doses are necessary for 
evaluating steady state PK because ritlecitinib has non stationary PK and steady state is 
achieved after >4 days of dosing. 
PK samples will be collected at times of pre-dose and post-dose times of 0.5, 1, 3 and 
8 hours. These sample times were selected to enable estimation of PK parameters of AUC, 
Cmax and Tmax using non-compartmental analysis methods. For calculation of AUCtau at 
steady state, the predose concentration will be used as an estimate for the concentration of 
24 hours post dose. 
4.2.1. Patient Input Into Design 
Surveys of children and parents were conducted to evaluate preferences and feasibility of the 
study, including study drug administration, blood draws, and clinic visit duration. 


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PFIZER CONFIDENTIAL 
Page 29 
 
 
4.2.2. Diversity of Study Population 
Reasonable attempts will be made to enroll participants with the distribution of 
characteristics with respect to race, ethnicity, and age to ensure the study population is 
representative of the patient population that will use study intervention in clinical practice. 
4.2.3. Adjudication Committee 
This protocol will use an independent endpoint adjudication committee to determine whether 
certain investigator-reported events meet the definition of disease-related safety endpoints, 
using predefined endpoint criteria. Further information about this endpoint adjudication 
committee is provided in a charter, including a description of the scope of the committee’s 
responsibilities, the process and definitions to be utilized by the committee for adjudication, 
and communication plan including timelines. 
The following adjudication committees are used for the B798 program: 
• Opportunistic Infection Review Committee (OIRC), 
• Cardiovascular Event Adjudication Committee (CVEAC), 
• Malignancy Adjudication Committee (MAC), and 
• Neurosafety Event Adjudication Committee (NSEAC). 
Events requiring submission to an adjudication/review committee will be identified by: 
• Pfizer Study Team or designee during the review of participant data listings or by 
• Site monitors during routine monitoring of participant’s study records 
Additional types of events for review and adjudication may be identified by Pfizer. 
The Pfizer Study Team or designee will notify the study site of any such events should they 
be identified. 
The Pfizer Study Team or designee will provide a listing of specific documents needed to 
support event adjudication by the Adjudication/Review Committees. Obtaining and 
submitting the documentation will be the responsibility of the study site. 
Event documentation will vary with the event requiring adjudication and may include (but 
not limited to): hospital discharge summaries, operative reports, clinic notes, ECGs, 
diagnostic tests, pathology reports, autopsy reports and death certificate information, as 
applicable. 
Review of redacted copies of these documents by the Pfizer Study Team or designee may be 
performed, where ethically and scientifically justified and permitted by local regulations, to 
ensure completeness and quality of event documentation prior to submission to 
Adjudication/Review Committees. 


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4.2.4. E-DMC 
This study will use an E-DMC. The E-DMC will be responsible for ongoing monitoring of 
the safety of participants in the study according to the charter. The recommendations made 
by the E-DMC will be forwarded to the appropriate authorized Pfizer personnel for review 
and final decision. Pfizer will communicate such decisions, which may include summaries of 
aggregate analyses of endpoint events and of safety data that are not endpoints, to regulatory 
authorities and investigators, as appropriate. 
Composition of the E-DMC and the processes under which the E-DMC operates will be 
documented in the E-DMC charter. 
4.2.5. Choice of Contraception/Barrier Requirements 
Human reproductive safety data for ritlecitinib are limited and not enough to evaluate the risk 
for treatment related birth defects. In animal studies (rats and rabbits) fetotoxicity and fetal 
malformations were observed at exposures equivalent to 49 to 55 times the MRHD. No 
developmental toxicity was observed at exposures equivalent to 12 to 16 times the MRHD. 
Although the suspicion for human teratogenicity based on the intended pharmacology of the 
compound is minimal, the use of a highly effective method of contraception in WOCBP is 
required (see Appendix 4). 
The definition of WOCBP is provided in Section 10.4.3. 
4.3. Justification for Dose 
The selected dose for Study B7981031 is 20 mg QD. The rationale for this dose selection is 
as follows. 
 
Study B7981015 was performed in adults and adolescents and evaluated 5 dosing regimens 
of ritlecitinib: 
• 50 mg and 30 mg with and without a loading dose of 200 mg 
• A 10 mg dose without loading dose. 
The results from the above study indicated that the 10 mg dose did not differentiate from 
placebo, while the doses of 50 and 30 mg with and without loading dose demonstrated 
significant efficacy over placebo. The 50 mg dose (without loading dose) was identified as 
the regimen with optimal benefit:risk for adults and adolescents for registration. 
 
The dose determination to support dosing in this study was based on the following 
considerations: 
 
1. The systemic exposure data generated in B7981015 for adult and adolescent participants 
were utilized to derive the dose recommendations for children (6 to <12 years of age) 
using population PK modeling and simulation analysis. 


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2. The dose selected for children 6 to <12 years of age in Study B7981031 is expected to 
provide lower exposures than the 50 mg dose in the B7981015 study in adults and 
adolescents. 
The dose of 20 mg selected for evaluation in this PK, PD study is predicted to provide 
exposures in children 6 to <12 years of age approximating the exposure of a 30 mg dose in 
adults and adolescents. The dose of 20 mg is considered to be adequate to meet the objectives 
of the study to characterize of PK of ritlecitinib in children. 
 
4.4. End of Study Definition 
The end of the study is defined as the date of the completion of the last scheduled procedure 
(as shown in the SoA) for the last participant in the trial, globally. 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. If a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation is considered appropriate 
for the present study and subsequent screening in the planned long-term study. 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. 
Pfizer will review eligibility criteria verified by the investigator or qualified designee to 
confirm that participants meet study eligibility criteria before they are enrolled into enrolled 
into the study. The enrollment approval process will be initiated for a participant after an 
informed consent document has been signed and the investigator or qualified designee has 
assessed the participant as eligible. The enrollment approval will be based on review of 
CRF/system data. 
There are no enrollment minimums or maximums in any country. 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age and Sex: 
1. 
Participants who are 6 to <12 years old at the time of the screening visit. Refer to 
(Section 10.4) for reproductive criteria for male and female participants. 
Disease Characteristics: 


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2. 
A diagnosis of severe AA, including AT and AU, with ≥50% scalp hair loss due to AA 
(ie, a SALT score of ≥50) at both the Screening and Baseline visits, without evidence of 
terminal hair regrowth within the previous 12 months. 
Other Inclusion Criteria: 
3. 
For study participants in the EU/UK only: 
History of clinical response failure to AA treatment (such as topical, off-label 
pharmacologic, or hairpiece prosthetics) 
AND 
a. Participants with a history of psychological counseling for AA (as evidenced by 
Screening AA assessments) in the past year prior to Screening 
Participants are eligible if current psychosocial impairment is confirmed by 
administering all four instruments listed below and meeting the specified thresholds: 
• PROMIS® Parent Proxy Anxiety Symptoms: T-score 60-70 
• PROMIS® Parent Proxy Depressive Symptoms: T-score 60-70 
• BRIEF®2 (BRI, ERI, CRI): T-score 60-70 on any one of the 3 components of the 
BRIEF®2. 
• Modified CDLQI (score of >7) 
NOTE: For T-scores higher than 70 (PROMIS and BRIEF) see exclusion criterion 7. 
OR 
b. Participants with no history of psychological counseling for AA in the past year prior 
to Screening 
In order to be eligible for this study, participants must: 
• Have a T-score of 60-70 on any one of the 3 instruments (PROMIS®-Anxiety 
Symptoms or PROMIS®-Depressive Symptoms or any one of the 3 components 
of BRIEF®2) 
• Complete at least 5 psychological counseling sessions for AA prior to Screening 
• Be re-evaluated after completion of the psychological counseling and have a 
T-score of 60-70 on any one of the three instruments (PROMIS®-Anxiety 
Symptoms or PROMIS®-Depressive Symptoms or any one of the 3 components 
of BRIEF®2) 


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NOTE: For T-scores higher than 70 (PROMIS and BRIEF) see exclusion criterion 7. 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions: 
1. A known congenital cause of AA, other systemic diseases that may cause hair loss (eg, 
lupus erythematosus, thyroiditis, systemic sclerosis, lichen planus, etc) or other etiology 
of hair loss (eg, telogen effluvium, androgenetic alopecia, etc). 
2. Conditions that may impact absorption or metabolism of IP (eg, celiac disease, 
cholecystectomy or gastrectomy). 
3. Pre-existing hearing loss, or sudden hearing loss, or middle or inner ear disease such as 
chronic otitis media, cholesteatoma, Meniere’s disease, labyrinthitis, or other auditory 
condition that is considered acute, fluctuating or progressive. If hearing loss is due to 
acute otitis media, participants can be rescreened at a later date, once the condition 
resolves. 
4. Any present malignancies or history of malignancies, history of any lymphoproliferative 
disorder such as EBV related lymphoproliferative disorder, history of lymphoma, history 
of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease, 
5. Active autoimmune disorder (other than AA), known immunodeficiency disorder, or a 
first degree relative with a hereditary immunodeficiency. 
6. History (one or more episodes) of CMV, varicella, herpes zoster (shingles) or 
disseminated herpes simplex. A history of uncomplicated herpes simplex is not 
exclusionary. 
7. Other medical or psychiatric condition (including recent [within the past year] or active 
suicidal ideation/behavior) that may increase the risk of study participation or, in the 
investigator’s judgment, make the participant inappropriate for the study, including but 
not limited to: 
• For participants in the EU/UK with scores of >70 on the PROMIS® or any 
component of the BRIEF®2, or with previous history of suicidal behaviors in the past 
5 years (“Yes” answer for events that occurred in the past 5 years) to any of the 
suicidal behavior items of the C-SSRS or with any lifetime history of serious or 
recurrent suicidal behavior, a risk assessment must be performed and documented by 
a qualified mental health professional to assess whether it is safe to participate in the 
trial. 
• For participants in the US and other non-EU/UK countries with a previous history of 
suicidal behaviors in the past 5 years (“Yes” answer for events that occurred in the 
past 5 years) to any of the suicidal behavior items of the C-SSRS or with any lifetime 


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history of serious or recurrent suicidal behavior, a risk assessment must be performed 
and documented by a qualified mental health professional to assess whether it is safe 
to participate in the trial. 
• For participants in the US and other non-EU/UK countries: Clinically significant 
depression per the CDRS-R (T-score ≥40). 
• History of or presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 
8. Trisomy 21 (EU/UK only) 
Prior/Concomitant Therapy: 
9. Current use of any prohibited concomitant medication(s) or history of discontinuation of 
treatment with a JAK inhibitor due to a treatment related adverse event. Refer to 
Section 6.9. 
Prior/Concurrent Clinical Study Experience: 
10. Previous administration with an investigational product (drug or vaccine) within 30 days 
(or as determined by the local requirement) or 5 half-lives preceding the first dose of 
study intervention used in this study (whichever is longer). 
Diagnostic Assessments: 
11. Any laboratory abnormality that may increase the risk of study participation or, in the 
investigator’s judgment, make the participant inappropriate for the study, including but 
not limited to the following: 
• Renal dysfunction defined as: 
• eCrCl normalized to BSA: Confirmed eCrCl <60 mL/min/1.73 m2 based on 
Modified Schwartz equation (pediatric patients 2 to <12 years of age). See 
Appendix 6. 
• Hepatic dysfunction defined as: 
• Total bilirubin >1.5 × ULN (except for Gilbert’s syndrome) 
• AST >1.5 × ULN 
• ALT >1.5 × ULN 
• Hematologic abnormalities defined as: 
• Absolute neutrophil count <1.2 × 109/L (<1200/mm3) 


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• Hemoglobin <11.0 g/dL 
• Platelet count <150 × 109/L (<150,000/mm3) 
• Absolute lymphocyte count of <0.8 × 109 /L (<800/mm3) 
• Any infection requiring hospitalization, parenteral antimicrobial therapy or judged 
to be opportunistic by the investigator within the 3 months prior to the first dose 
of IP or infection with HIV, hepatitis B or hepatitis C viruses according to 
protocol specific testing algorithms or active acute or chronic infection requiring 
treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or 
antifungals within 4 weeks prior to Day 1 or superficial skin infection within 
1 week prior to Day 1, or evidence of untreated or inadequately treated active or 
latent mycobacterium TB infection or a positive QFT test (or equivalent) 
performed within 3 months prior to first dose of IP. QFT (or equivalent) test 
should be performed during screening if not performed within past 3 months (see 
Appendix 9). 
NOTE: participants may be rescreened after the infection resolves. 
12. Current or recent history of clinically significant severe, progressive, or uncontrolled 
renal (including but not limited to active renal disease or recent kidney stones), hepatic, 
hematological, gastrointestinal, metabolic, endocrine (particularly thyroid disease which 
can be associated with hair loss), pulmonary, cardiovascular, psychiatric, 
immunologic/rheumatologic or neurologic disease; or have any other severe acute or 
chronic medical or psychiatric condition or laboratory abnormality that may increase the 
risk associated with study participation or investigational product administration, or 
interfere with the interpretation of study results; or in the opinion of the investigator or 
Pfizer (or designee), the participant is inappropriate for entry into this study, or 
unwilling/unable to comply with study procedures and lifestyle requirements. Significant 
trauma or major surgery within 1 month of the first dose of IP is also exclusionary. 
Other Exclusion Criteria: 
13. Not up to date with all age appropriate vaccines, including 2-dose vaccination for 
varicella, or vaccination with attenuated live vaccine within 6 weeks of first dose of IP. 
14. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members. 
5.3. Lifestyle Considerations 
5.3.1. Contraception 
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant 


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and their partner(s) from the permitted list of contraception methods (see Appendix 4, 
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. At time points indicated in the SoA, the investigator or designee will inform the 
participant of the need to use an highly effective contraception consistently and correctly and 
document the conversation and the participant’s affirmation in the participant’s chart. 
Participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception, considering that their risk for pregnancy may have changed since 
the last visit. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 
alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner. 
5.3.2. Meals and Dietary Restrictions 
There are no restrictions regarding food or drink either before or after dosing. Participants 
should follow their regular diet. 
5.3.3. Caffeine, Alcohol, and Tobacco 
 
Participants will abstain from ingesting caffeine or xanthine containing products (tea, coffee, 
cola drinks, etc) during the study (from 24 hours prior to first dose until collection of final 
PK sample). Use of alcohol or tobacco is not expected in this population and should not be 
used during the study. 
 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, and any SAE. 
Screen failure data are collected and remain as source and are not reported on the CRF. 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
be rescreened if at the time of the initial screening they were disqualified for not meeting 
exclusion criteria 12, 10, 11 (hematological abnormalities only) or 16 and 17. 
Participants not meeting inclusion criteria 12, 10, 11 may be rescreened after the exclusion 
interval is over as follows: 
• exclusion criterion # 12 – 30 days for significant trauma, 
• exclusion criterion # 10 – 30 days or 5 half-lives for investigational products 


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• exclusion criterion # 11 – hematological abnormalities 
Participants not meeting exclusion criteria 11 may be rescreened after the exclusion interval 
is over and the infection resolves as follows: 
• exclusion criterion # 11 – infection requiring hospitalization or parenteral treatment – 
3 months after the infection resolves 
• exclusion criterion # 11 – Active acute or chronic infection requiring treatment – 28 
days after the infection resolves (exception for superficial skin infections – 7 days 
after the infection resolves) 
At the rescreening visit, all screening procedures must be repeated, including lab tests and all 
other eligibility criteria must be met. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study interventions are all prespecified investigational and medical devices, and other 
interventions (eg, surgical and behavioral) intended to be administered to the study 
participants during the study conduct. 
 
For the purposes of this protocol, study intervention refers to ritlecitinib. The daily dose is 
20 mg once daily and the treatment will last up to 7 days. 
6.1. Study Intervention(s) Administered 
The study includes a screening period of up to 28 days, a 7-day interventional period, and a 
28-35 day follow-up period. The duration of study participation for each participant is 
approximately 9-10 weeks. 
 
Study Intervention(s) 
Intervention Name 
Ritlecitinib (PF-06651600) 
Arm Name 
(group of participants receiving a specific 
treatment or no treatment) 
Active study medication 
Unit Dose Strength(s) 
20 mg 
Route of Administration 
Oral 
Use 
Experimental 
IMP or NIMP/AxMP 
IMP 


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Study Arm(s) 
Arm Title 
Active study medication 
Arm Type 
Active study medication 
Arm Description 
Participants will receive study medication, 20 mg per day, for 7 days. 
Each site will receive an initial shipment with enough IP for two participants. Replacements 
will be provided to the study site as the initial supply is used or expired. 
6.1.1. Administration 
Ritlecitinib will be provided to the study sites as capsules. 
For administration, the capsules will be dissolved in water and the contents of the capsule in 
water will be taken. No other liquids are allowed (carbonated water, soda, fruit juices). DO 
NOT ADD SUGAR OR ANY SWEETENER. 
The first dose will be administered at the study site, in presence of the investigator or 
designee, who will instruct the participant and the parents/legal guardians, in detail, on how 
the treatment should be taken. 
VERY IMPORTANT: 
a. The Investigational Product must be administered immediately after preparation and 
never stored. 
b. The capsule must be dissolved in water according to the dosing administration 
instructions. 
c. Treatment will be administered in the morning, after breakfast. 
d. Time of the administration will be documented on a daily basis. The Investigator or 
designee will collect this information during the study visits and record in the Case 
Report Form. 
e. If vomiting occurs within 1 hours after administration of ritlecitinib, it must be 
documented and reported to the site as a missed dose. If a dose is vomited, a 
replacement dose should not be administered. 
All episodes of vomiting will be reported as Adverse Events, regardless of how long 
after the administration of ritlecitinib they occurred. 
6.2. Preparation, Handling, Storage, and Accountability 
1. The investigator or designee must confirm that appropriate conditions (eg, 
temperature) have been maintained during transit for all study interventions received 
and any discrepancies are reported and resolved before use of the study intervention. 


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2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention. 
3. 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 upon 
return to business. 
4. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with actions taken. The site should actively 
pursue options for returning the study intervention to labeled storage conditions, 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 excursion definition and information to 
report for each excursion will be provided to the site in the IP manual. 
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label. Site staff will instruct participants on the proper storage 
requirements for take home study intervention. See the Investigational Product 
Manual for storage conditions of the study intervention once reconstituted. 
6. Study interventions should be stored in their original containers. 
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records), such as the IPAL or sponsor-approved equivalent. All study 
interventions will be accounted for using a study intervention accountability 
form/record. All ritlecitinib that is taken home by the participant, both used (empty 
capsules) and unused capsules, must be returned to the investigator by the participant. 
Returned study intervention must not be re-dispensed to the participants. 
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the Investigational Product 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 IPM. 


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6.2.1. Preparation and Dispensing 
A qualified staff member will dispense the study intervention in the bottles provided, in 
quantities appropriate according to the SoA. A second staff member will verify the 
dispensing. The participant’s parents/legal guardians will be instructed to maintain the 
product in the bottle provided throughout the course of dosing and return the bottle to the site 
at the next study visit. The investigational product must be maintained in a locked space, out 
of reach of children. 
The first dose of ritlecitinib will be administered at the study site, mixed with water (not 
carbonated). 
Specific preparation and administration instructions will be provided in the IPM. 
The participant’s parents/legal guardians will be instructed on how to prepare and administer 
the next 5 doses at home, as explained in the protocol Section 6.1.1. 
The last dose of IP (the 7th dose) will be administered at the study site, in the presence of the 
investigator or designee. The first PK sample will be drawn before administration, then at 
0.5, 1, 3 and 8 hours after administration. 
In the event the content of a capsule is partially spilled, all the content must be discarded and 
another capsule will be used. In the unlikely event that the participant will run out of IP 
(accidental spilling, bottle lost, etc.) the site must be contacted immediately and, if possible, 
replacement IP will be provided. 
All used (empty) capsules must be kept and returned at the EOT visit, for drug accountability 
purposes. 
6.3. Assignment to Study Intervention 
This is an open-label study. The investigator’s knowledge of the treatment assignment must 
not influence the decision to enroll a particular participant or affect the order in which 
participants are enrolled. Given the small number of participants and the nature of the study 
(PK, PD) it is very unlikely that the investigator decisions may be affected by bias. 
6.4. Blinding 
Not applicable. This is an open-label study. 
6.5. Study Intervention Compliance 
Ritlecitinib will be dispensed to the participants for the whole duration of the treatment 
(7 days). The first and last dose will be administered at the study site. 
Doses 2 through 6 will be taken at home. 
The investigator or designee will provide detailed instructions on how to prepare and 
administer the IP. 


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VERY IMPORTANT: 
a. If vomiting occurs within 1 hours after administration of ritlecitinib, it must be 
documented and reported to the site. 
If the preparation containing the a whole capsule is not ingested completely, the event must 
be documented and reported at the following visit. Do not use another capsule on the same 
day. Wait until the next day for the following dose. 
When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit (phone visits on Days 2, 4 and 6, site visit on 
Day 7). During the phone visits, the investigator or designee will make sure the IP was 
administered as directed. On Day 7, compliance will be assessed by counting the returned 
capsules (if any). All compliance data will be recorded in the Case Report Form. Deviations 
from the prescribed dosage will be recorded in the Case Report Form and documented as 
protocol deviations. 
A record of the number of ritlecitinib capsules dispensed to and taken by each participant 
must be maintained and reconciled with study intervention and compliance records. 
Intervention start and stop dates, including dates for intervention delays and/or dose 
reductions, will also be recorded in the CRF. 
PK samples will not be collected for under-compliant participants. The site must report the 
reason for undercompliance (including medication errors, if appropriate). The participant will 
complete the safety follow-up as described in the SoA. 
6.5.1. Missed doses 
Between Days 2 and 5, if a dose is missed (not more than one), treatment can be continued as 
scheduled. The date when the dose was missed and the reason must be reported to the site. 
If more than one dose is missed (consecutively or not), participants become unevaluable for 
PK. Once a second dose is missed, treatment must be discontinued and no additional doses of 
IP can be taken. The site must be notified as soon as possible. An EOT visit must be 
scheduled as soon as possible. During the visit, all study procedures, as outlined in the SoA, 
will be conducted, with the exception of the PK sample collection. 
If the dose on Day 6 is missed, the participant cannot be evaluated for PK. Study treatment is 
considered Early Discontinued. On Day 7, no study drug is to be administered. An EOT visit 
will be conducted and all study procedures will be completed, with the exception of the PK 
sample collection. 
In all cases, a safety follow-up contact will be conducted 28-35 days after the last dose of IP. 
6.6. Dose Modification 
Dose modification is not permitted during the study. 


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6.7. Continued Access to Study Intervention After the End of the Study 
No study intervention will be provided to participants after the end of their study 
participation. It is expected that participants will be treated as required with standard-of-care 
treatments, as advised by their usual care physician. 
6.8. Treatment of Overdose 
For this study, any dose of ritlecitinib greater than 20 mg per day will be considered an 
overdose. 
There is no specific treatment for an overdose. 
In the event of an overdose: 
The participant or parent/caregiver should contact the site immediately and report: the dose 
taken, the date and time of the day and any symptoms experienced after taking the IP. 
The investigator should: 
1. Contact the study medical monitor within 24 hours. 
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up. 
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 
4. Overdose is reportable to Pfizer Safety only when associated with an SAE. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the study medical monitor as needed based on the clinical evaluation of the 
participant. 
6.9. Prior and Concomitant Therapy 
6.9.1. Prohibited Medications 
Any of the following treatment regimens specified in the timeframes outlined below: 
a. At any time: previous use of any non-B-cell selective lymphocyte-depleting agent (eg, 
alefacept, alemtuzumab). 
b. Within 6 months of first dose of study intervention or 5 half-lives (if known), or until 
lymphocyte count returns to normal, whichever is longer: any B-cell-depleting agents, 
including but not limited to rituximab. 
c. Within 12 weeks of first dose of study intervention or 5 half-lives (if known), whichever 
is longer: 
• Any JAK inhibitor for use in any disease indication (including topical preparation) 


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• Immunomodulatory biologic agents. 
Note: Discontinuation of any JAK inhibitor due to a treatment-related adverse event is 
exclusionary (see exclusion 9). 
d. Within 8 weeks of first dose of study intervention or within 5 half-lives (if known), 
whichever is longer: 
• Immunosuppressants (eg, cyclosporine A, azathioprine, MTX, sulfasalazine, 
MMF, everolimus, ibrutinib). 
• Oral or injectable steroids. 
e. Within 6 weeks of first dose of study intervention: vaccination with attenuated live 
vaccine. 
f. Within 4 weeks of first dose of study intervention or 5 half-lives (if known), whichever 
is longer: prohibited CYP3A inducers as described in Section 6.9.2. 
g. Within 1 week of first dose of study intervention: 
• Herbal medications with either unknown properties or pharmaceutical properties 
that impact PK 
• Prohibited CYP3A and CYP1A2 substrates as described in Section 6.9.2 (within 
7 days or 5 half-lives, whichever is longer). 
6.9.2. Prohibited and Permitted Concomitant CYP3A Inducers, and CYP3A and 
CYP1A2 Substrates 
This is not an all-inclusive list. Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that are moderate to potent CYP3A 
inducers or sensitive or moderate sensitive CYP3A or CYP1A2 substrates. If a medication 
is a sensitive or moderate sensitive CYP3A or CYP1A2 substrate and is not listed below as 
prohibited or permitted, consultation with the Sponsor is required. 
6.9.2.1. Prohibited Concomitant CYP3A Inducers and Substrates 
Refer to Table 3. 


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6.9.2.2. Permitted Concomitant CYP3A Substrates 
 
Sensitive CYP3A Substrates## 
Moderate Sensitive CYP3A 
Substrates§ 
Alfentanil 
Midazolam 
Alprazolam 
Avanafil 
Naloxegol 
Atorvastatin 
Buspirone 
Quetiapine 
Colchicine 
Darifenacin 
Sildenafil 
Rivaroxaban 
Eletriptan 
Simvastatin 
Tadalafil 
Eplerenone 
Ticagrelor 
Felodipine 
Triazolam 
Lovastatin 
Vardenafil 
Lurasidone 
## Sensitive CYP3A substrates are drugs that demonstrate an increase in AUC of ≥5-fold with strong index inhibitors 
of a given metabolic pathway in clinical DDI studies. 
Topical (including skin or mucous membranes) application of antimicrobial and antifungal medications is permitted. 
§ Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold. 
 
6.9.2.3. Prohibited Concomitant CYP1A2 Substrates 
Refer to Table 4. 
6.9.2.4. Permitted Concomitant CYP1A2 Substrates 
 
Sensitive CYP1A2 Substrates 
Moderate Sensitive CYP1A2 Substrates 
Alosetron 
Duloxetine 
Melatonin 
Ramelteon 
Tasimelteon 
Clozapine 
Theophylline 
Olanzapine 
Rasagiline 
Ropivacaine 
Sensitive substrates are drugs that demonstrate an increase in AUC of ≥5-fold with strong index 
inhibitors of a given metabolic pathway in clinical DDI studies. Topical (including skin or mucous 
membranes) application of antimicrobial and antifungal medications is permitted. 
Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold. 
 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Permanent Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention may include the following: Adverse 
Event, Protocol Deviation, Withdrawal of Consent, Pregnancy, and/or COVID-19. 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant should remain in the study 
to be evaluated for safety 28 to 35 days after the last dose of IP. See the SoA for data to be 


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collected at the time of discontinuation of study intervention and follow-up for any further 
evaluations that need to be completed. 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
7.1.1. Adverse Event 
Study intervention must be permanently discontinued, and the EOT Visit completed, if the 
participant experiences: 
• Serious infections (defined as any infection [viral, bacterial, and fungal] requiring 
parenteral antimicrobial therapy or hospitalization for treatment or meeting other 
criteria that require the infection to be classified as serious adverse event); 
• Treatment related SAEs; 
• Other serious or severe AEs, at the discretion of the investigator or sponsor. 
All Adverse Events leading to permanent discontinuation of IP must be documented in the 
CRF indicating action taken with study drug as permanently discontinued. The EOT CRF 
page must show reason for treatment discontinuation as “Adverse Event”. 
7.1.2. Protocol Deviation 
Study intervention must be permanently discontinued, and the EOT Visit completed for 
protocol deviations such as: 
• Use of prohibited medication 
• Not meeting all eligibility criteria (eg, incidental monitoring findings during phone 
calls) 
• Treatment under-compliance (missing more than one dose of IP between Day 2 and 5, 
missed dose on Day 6). 
7.1.3. Withdrawal of Consent 
Participants may withdraw from the study at any time. If the consent is withdrawn during the 
treatment period (Days 1 to 7), an EOT visit must be completed. If the withdrawal is 
complete, from all study procedures, an EOS visit study must be conducted at the same time. 


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7.1.4. Pregnancy 
Due to the age of the participants and the short duration of treatment there is a very low 
probability for a pregnancy to occur during this trial. 
Also, there will be no pregnancy testing between first and last dose of IP, so pregnancy 
cannot be detected during treatment. 
7.1.5. COVID-19 
If a study participant is diagnosed with COVID-19 infection during this study, study 
treatment will be permanently discontinued and the event will be reported as an AE or SAE, 
as appropriate. 
 
An EOT visit must be conducted as soon as possible. The participant will complete the safety 
follow-up visit 28-35 days after the last dose of IP. 
7.1.6. Temporary Discontinuation 
This is a PK and PD study. Ideally, all seven doses must be taken so the PK analyses can be 
conducted at the end of the treatment. 
Temporary discontinuations are allowed only from Day 2 and until Day 5, and only for one 
day. If two or more doses (consecutive or not) are missed between Day 2 and Day 5, the 
participant becomes unevaluable for PK and PD. 
If study treatment must be interrupted for any reason, an end of treatment visit will be 
completed as soon as possible, followed by an End of Study visit, at 28-35 day after the last 
dose of IP. 
7.2. Participant Discontinuation/Withdrawal From the Study 
Participants may be withdrawn from the study at any time at the request of their parents/legal 
guardians. 
If a participant decides to discontinue treatment for any reason, all efforts should be made to 
conduct a safety follow-up visit 28 to 35 days after the last dose of IP. If not possible 
(withdrawal of consent, etc.) an Early discontinuation visit will be completed. All EOT and 
End of Study procedures will be conducted according to the SoA. 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. 


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If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent/assent for any further 
contact with them 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 the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the participant wishes to and/or should 
continue in the study; 
• Before a participant is deemed lost to 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, the participant will be considered 
to have withdrawn from the study. 


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8. STUDY ASSESSMENTS AND PROCEDURES 
8.1. Administrative and Baseline 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. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
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 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 they have 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. 
Psychological assessments will be conducted as described in the SoA. For additional details, 
refer to Appendix 11 to Appendix 15. 
Severity of alopecia will also be assessed at screening (SALT) and documented in the CRF. 
The total blood sampling volume for individual participants in this study is approximately 
20 ml for the whole study. 


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Study Visit 
Test 
Screening 
EOT 
Screening 
Hematology 
0.5 ml 
0.5 ml 
Blood chemistry 
0.5 ml 
0.5 ml 
QFT 
1 ml 
IP-10 
1 ml 
1 ml 
Lymphocyte subsets 
2 ml 
2 ml 
Hepatitis B and C 
2 ml 
HIV 
2 ml 
Pregnancy (serum) 
2 ml 
Day 7 
PK 
5 ml (5 × 1 ml) 
Total Blood Sampling Volume 
11 ml 
9 ml 
 
Additional blood tests may be required, at the Investigator’s discretion. 
TBV is equal to the participant’s weight in kg multiplied by the estimated mL/kg (80-90 
ml/kg for children). EU and WHO guidelines suggest that no more than 1% of TBV should 
be drawn in a 24-hour period and no more that 3% of TBV should be drawn over 4 weeks. 
For example, the TBV of a 6 year-old child at approximately the 5th percentile for weight, 
weighing 17 kg, is 1,360-1,530 mL. Per the criteria of the EU and WHO guidelines, total 
blood sampling volume limits for this child are 14 -15 mL of blood in 24 hours and 41-46 
mL of blood in 4 weeks. 
8.1.1. Baseline Procedures 
All procedures listed in the SoA must be conducted at this visit. 
8.1.2. Telehealth Visits 
Screening, Baseline and EOT visits must be conducted at the study site. 
Telehealth visits will be used to assess participant safety and collect data points. Telehealth 
includes the exchange of healthcare information and services via telecommunication 
technologies (eg, audio, video, videoconferencing software) remotely, allowing the 
participant and the investigator to communicate on aspects of clinical care, including medical 
advice, reminders, education, and safety monitoring. 
Study Visits at Days 2, 4 and 6, and the EOS (Follow-up) visit will be conducted by phone. 
Study data will be collected as described in the SoA. 
The following assessments must be performed during a telehealth visit (see the SoA): 
• Review and record study intervention(s), including compliance and missed doses. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.4. 


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• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
• Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4. 
Study participants must be reminded to promptly notify site staff about any change in their 
health status. 
8.1.3. Home Health Visits 
A home health care service may be utilized to facilitate scheduled visits. Home health visits 
include a healthcare provider conducting an in-person study visit at the participant’s location, 
rather than an in-person study visit at the site. The following may be performed during a 
home health visit (see the SoA): 
• Review and record study intervention(s), including compliance and missed doses. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.4. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
• Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4. 
• On day 7, the last two PK samples (3 and 8 hours post dose) may be collected at 
home. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
8.2. Efficacy Assessments 
This is a PK, PD study. No efficacy assessments will be performed. 
8.2.1. Rater Qualifications 
Clinical evaluations will be completed at screening, for eligibility purposes, as follows: 
• SALT score 
• Taste Assessment Questionnaire 
• The C-SSRS suicidal ideation and behavior risk assessment 
• CDRS 


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• WISC-V (Wechsler Intelligence Scale for Children - 5th edition) 
The Taste Assessment questionnaire is a simple assessment that can be conducted by the 
Study Coordinator or designee. 
All other assessments require experienced personnel, with skills in interacting with children. 
For C-SSRS, specific documented training is required. 
Additional details are provided in specific appendices and study manual, for each assessment. 
For C-SSRS assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study (see Appendix 11 for details). 
Training material will be provided to each site, as appropriate. The level of experience with 
the target population (or equivalent), specific scale experience (or equivalent), and 
certification required (if applicable) will be listed and used to determine whether a rater is 
approved for a given assessment. The rater must become certified to perform selected study 
assessments before they can participate in the conduct of the study. For specifically defined 
assessments, rater training and standardization exercises may be conducted, and written 
documentation will be provided by the site for each rater’s certification. In return, each site 
will be provided written documentation outlining each rater’s certification for specific study 
assessments. Recertification may be required at periodic intervals during the study. The raters 
who administer specific study assessments will be documented in a centralized location and 
all site staff who administer ratings will be verified in the site study documentation during 
the conduct of the study. 
To ensure consistency and reduce variability, each participant should have all assessments 
conducted by the same rater. Every effort will be made to have all assessments completed by 
the same rater. 
8.3. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety 
measurements may be obtained at any time during the study to assess any perceived safety 
issues. 
8.3.1. Physical Examinations 
A complete physical examination including height and weight will be performed at Screening 
and include, at a minimum, an assessment of the following: general appearance, skin, lymph 
nodes cardiovascular, respiratory, gastrointestinal and neurological and musculoskeletal 
systems. 
Brief physical exams will be conducted at Baseline and EOT and Early Study Termination. 
Severity of alopecia will also be assessed at screening as described in Appendix 10 – SALT. 
A minimum of 50% scalp hair loss due to AA is required to be eligible for this study. 


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Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Section 8.4.1 to Section 8.4.3. 
8.3.2. Vital Signs 
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Section 8.4.1 to Section 8.4.3. 
8.3.2.1. Blood Pressure and Heart Rate 
BP and HR measurements will be assessed in supine position with a completely automated 
device and using a pediatric cuff of the appropriate size. Manual techniques will be used only 
if an automated device is not available. 
BP and HR measurements should be preceded by at least 5 minutes of rest with the 
participant in a supine position, in a quiet setting without distractions. 
Vital signs will be taken before blood collection for laboratory tests and consist of a single 
measurement of HR and 3 BP measurements (3 consecutive BP readings will be recorded at 
intervals of at least 1 minute apart). The average of the 3 BP readings will be recorded on the 
CRF. 
8.3.3. 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 significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that 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 significant and abnormal during 
participation in the study or within 8 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 study medical monitor. 


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If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
DILI. 
See Section 10.6.1 for instructions for laboratory testing to monitor kidney function and 
reporting laboratory test abnormalities. 
8.3.3.1. Alternative Facilities for Clinical Safety Laboratory Assessment 
Protocol-specified safety laboratory evaluations must be conducted at a Central Laboratory. 
Alternatively, additional tests required for diagnosis (such as documentation of Serious 
Adverse Event) can be conducted at a local laboratory, in specific circumstances (time 
constraints, shipping unavailable, etc.) The local laboratory may be a standalone institution 
or within a hospital. 
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/ 
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible. The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should 
be recorded on the CRF. 
8.3.4. Pregnancy Testing 
All WOCBP participating in this study must have a pregnancy test performed at Screening, 
Baseline and EOT visit. Definition of a WOCBP participant is provided in Section 10.4.3. 
A serum pregnancy test is required at screening. Following screening, pregnancy tests may 
be urine or serum tests, and must have a sensitivity of at least 25 mIU/mL. Pregnancy tests 
will be performed in WOCBP at the times listed in the SoA. Following a negative pregnancy 
test result at screening, appropriate contraception must be commenced and a second negative 
pregnancy test result will be required at the baseline visit prior to the participant’s receiving 
the first dose of ritlecitinib. Pregnancy tests will also be done whenever 1 menstrual cycle is 
missed during the active treatment period (or when potential pregnancy is otherwise 
suspected) and at the end of the study. Pregnancy tests may also be repeated if requested by 
IRBs/ECs or if required by local regulations. 
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy 
test is required. In such cases, the participant must be excluded if the serum pregnancy result 
is positive. 
The PI will review the results of the pregnancy test as soon as they are available and 
communicate the results to the parents/legal guardians within the next 24 hours. 
Notification of parents/legal guardians must comply with local regulations. 


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8.3.5. Suicidal Ideation and Behavior Risk Monitoring 
Suicidal Ideation and Behavior will be assessed at Screening using the C-SSRS (Columbia 
Suicide Severity Rating Scale – pediatric version, baseline assessment) version for pediatric 
patients 6 to 11 years old (Appendix 11). 
Due to the short duration of treatment, this assessment will be performed only at screening, 
for eligibility purposes. The assessment will not be performed at the Follow-up visit 
(28-35 days after the last study intervention administration). 
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of an AE and an SAE can be found in Appendix 3. 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant and 
parent/legal guardian 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. 
8.4.1. 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 undergoing any study-related procedure and/or receiving study 
intervention, through and including a minimum of 28 calendar days, except as indicated 
below, after the last administration of the study intervention. 
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator. 
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues 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. 


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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 permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and they consider 
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. 
8.4.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.4.1 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 its being available. 
8.4.1.2. 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 8.4.1, 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. 
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
8.4.2. 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. 
8.4.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 


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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 provided in Appendix 3. 
8.4.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements. 
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure. 
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness. 
8.4.5.1. Exposure During Pregnancy 
Due to the short duration of treatment and age of participants (6 to 11 years old) EDP is 
unlikely to occur. 


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An EDP occurs if: 
• A female participant is found to be pregnant while receiving or after discontinuing 
study intervention. 
• A male participant who is receiving or has discontinued study intervention 
inseminates a female partner. 
• A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are 
examples of environmental EDP: 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion. 
• A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion then inseminates his female partner prior to or around 
the time of conception. 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
• If EDP occurs in a participant/participant’s partner, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP Supplemental 
Form, regardless of whether an SAE has occurred. Details of the pregnancy will be 
collected after the start of study intervention and until 28 days after the last dose. 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file. 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported). 


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Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live‑born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 
• Spontaneous abortion including miscarriage and missed abortion should be reported 
as an SAE; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.4.5.2. Exposure During Breastfeeding 
An EDB occurs if:. 
• A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention. 
• A female nonparticipant is found to be breastfeeding while being exposed or having 
been exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports 
that she is breastfeeding after having been exposed to the study intervention by 
ingestion. 
The investigator must report EDB 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 EDB 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 EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB. 


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8.4.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the CT SAE Report Form, regardless of 
whether there is an associated SAE. Since the information about the occupational exposure 
does not pertain to a participant enrolled in the study, the information is not recorded on a 
CRF; however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file. 
8.4.6. Cardiovascular and Death Events 
Not applicable. 
8.4.7. Disease Related Events and/or Disease Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.4.8. Adverse Events of Special Interest 
AESIs for this study include serious or opportunistic infections, viral reactivation, decreases 
in lymphocytes or platelets, and dermatologic events, including urticaria and rash. 
AESIs are examined as part of routine safety data review procedures throughout the clinical 
trial and as part of signal detection processes. Should an aggregate analysis indicate that 
these prespecified events occur more frequently than expected, eg, based on epidemiological 
data, literature, or other data, then this will be submitted and reported in accordance with 
Pfizer’s safety reporting requirements. Aggregate analyses of safety data will be performed 
on a regular basis per internal SOP. 
All AESIs must be reported as an AE or SAE following the procedures described in 
Section 8.4.1 through 8.4.4. An AESI is to be recorded as an AE or SAE on the CRF. In 
addition, an AESI that is also an SAE must be reported using the CT SAE Report Form. 
8.4.8.1. Lack of Efficacy 
Not applicable. 
This is a PK, PD study. The participants will receive study treatment for 7 days. No 
therapeutic benefit is expected. 
8.4.9. 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. 
Ideally, all doses should be taken after breakfast, to ensure a 24 hour interval between dosing. 
Taking study treatment at a later time during the day is acceptable on Days 2, 3, 4, 5. On 
Treatment Day 6 the dose must be taken at breakfast, to ensure a 24 hour interval before the 


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last dose. Missing or taking the Day 6 dose at a later time may compromise the PK results 
and must be reported as a protocol deviation and a medication error. 
Missed doses on Days 2, 3, 4 and 5, even multiple must be reported as protocol deviation, but 
do not represent medication errors. 
Medication errors are recorded and reported as follows: 
 
Recorded on the 
Medication Error Page 
of the CRF 
Recorded on the 
Adverse Event Page 
of the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
All (regardless of whether 
associated with an AE) 
Any AE or SAE associated 
with the medication error 
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. 
• Administration of expired study intervention 
• Administration of study intervention that has undergone temperature excursions from 
the specified storage range unless it is determine by the sponsor that the study 
intervention under question is acceptable for use. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
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. 
In the event of a medication dosing error, the sponsor should be notified within 24 hours. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
8.5. Pharmacokinetics 
Blood samples to provide plasma for PK analysis will be collected into appropriately labeled 
tubes containing K2EDTA anticoagulant at times specified in the SoA section of the 


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protocol. Blood samples of approximately 1 mL, to provide approximately 0.5 mL plasma, 
will be collected for measurement of plasma concentrations of ritlecitinib. 
When possible, an IV canula will be used, to allow collection of all 5 samples with just one 
venipuncture. 
On Day 7, study participants who completed the treatment and are undergoing the PK sample 
collection may be allowed to leave the site and go home after collection of the 3rd sample 
(1 hour post dose) and the last two samples (3 and 8 hours post dose) can be collected at 
home. 
If a peripheral venous catheter was installed for collection of the first 3 PK samples, it must 
be removed before leaving the sites. The last two samples, 3 and 8 hours post dose, will be 
collected by separate venipuncture. 
Blood will be collected at the time points identified in the SoA section of the protocol. On 
the PK sampling visit (Day 7), participants will be asked about the dosing time on the day 
before the visits and the investigational site personnel will record it in the data collection 
tool (eg, CRF). Participants will be instructed to not take their daily dose at home on the PK 
sampling day, but to bring the dose to the investigational site for the PK sampling visit and 
they will be instructed at the site when to take their dose. The IP should be administered in 
the morning, at breakfast, to allow completion of the PK collection (8 hours) within site 
working hours. All efforts will be made to obtain the PK samples at the exact nominal time 
relative to dosing. For each blood sample collection, the allowable windows are as follows 
for times post dose: 0.5 hr (±10 min), 1 hr (±15 min), 3 hr (±20 min) and 8 hr (±30 min). 
The date and exact time of dosing and the sample collection will be entered into source 
document and data collection tool (eg, CRF), as well as the date and time of the previous 
dose (one day prior to the PK sampling day). Samples obtained outside the windows 
specified in the SoA will be considered a protocol deviation. 
• The plasma will be stored in appropriately labeled screw-capped polypropylene 
tubes at approximately -20°C or colder within 1 hour of collection. 
• Further details regarding the collection, processing, storage and shipping of the 
blood samples will be provided in the lab manual. 
• Samples will be analyzed using a validated analytical method in compliance with 
Pfizer standard operating procedures. 
• The PK samples must be processed and shipped as indicated to maintain sample 
integrity. Any deviations from the PK processing steps, including any actions taken, 
must be documented and reported to the sponsor. On a case-by-case basis, the 
sponsor may make a determination as to whether sample integrity has been 
compromised. Any sample deemed outside of established stability, or of 
questionable integrity, will be considered a protocol deviation. 
• As part of understanding the pharmacokinetics of the IP, samples may be used for 
metabolite identification and/or evaluation of the bioanalytical method. These 


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data will be used for internal exploratory purposes and will not be included in the 
clinical report. 
The shipment address and assay lab contact information will be provided to the Investigator 
site prior to initiation of the study. The central laboratory will provide collection materials 
and directions for packaging and shipment of samples and will forward samples to the 
contract analytical laboratory. The contract analytical laboratory will be provided with 
randomization codes so that only samples in the ritlecitinib treatment groups are assayed. 
Placebo samples may be assayed in the event of suspected error in participant 
randomization. 
Refer to the central lab vendor manual for further information. 
8.6. Genetics 
8.6.1. Specified Genetics 
Specified genetic analyses are not evaluated in this study. 
8.7. Pharmacodynamics 
PD samples will be collected at screening and Day 7 only. If treatment has been early 
discontinued or temporarily interrupted for more than one day, PD samples will not be 
collected at Day 7. 
The PD samples must be processed and shipped as indicated to maintain sample integrity. 
Any deviations from the PD processing steps, including any actions taken, must be 
documented and reported to the sponsor. On a case-by-case basis, the sponsor may make a 
determination as to whether sample integrity has been compromised. Depending on sampling 
and transport constraints, it is possible that not all biomarker samples will be collected in all 
study regions. 
All efforts will be made to obtain the PD samples at the exact nominal time relative to 
dosing. Please consult the laboratory manual(s) for final instructions on sample collection, 
storage, and shipping requirements. These manual(s) supersede the instructions listed in the 
applicable protocol sections. Samples that are handled according to the respective manual 
guidance are considered “per protocol”. 
Samples will be analyzed using fit for purpose or validated analytical methods in compliance 
with Pfizer standard operating procedures. 
As part of understanding the pharmacodynamics of the study drug and the disease under 
study, samples may be used for evaluation of the bioanalytical method. These data will be 
used for internal (ie, Pfizer) exploratory purposes and may not be included in the clinical 
report. 
8.7.1. Biomarkers 
Biomarkers are not evaluated in this study. 


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8.7.2. Samples for Interferon Gamma-Induced Protein 10 (IP-10) Analysis 
Blood samples to provide serum for the analysis of IP-10 will be collected into appropriately 
labeled tubes according to the times outlined in the SoA. IP-10 samples will be collected 
from all participants unless the exportation of these samples from the country of origin is 
prohibited by local regulators or IRB/EC decision. 
8.7.3. Samples for Fluorescence-Activated Cell Sorting Analysis (T Cell, B Cell, and NK 
Cell Subsets) 
Blood samples for the assessment of percent and absolute lymphocyte subsets will be 
collected and will be analyzed by FACS to identify T cell, B cell, and NK cell subsets 
according to the times outlined in the SoA. 
8.7.4. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study. 
8.7.5. Specified Protein Research 
Specified protein research is not included in this study. 
8.7.6. Specified Metabolomic Research 
Specified metabolomic research is not included in this study. 
8.7.7. Retained Research Samples for Biomarkers 
Not applicable. 
8.8. Immunogenicity Assessments 
Immunogenicity assessments are not included in this study. 
8.9. 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 the 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. Statistical Hypothesis 
No statistical hypothesis will be tested in this study. 


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9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
 
Population 
Description 
PK Concentration 
The PK concentration population is defined as all participants 
treated who have at least 1 concentration. 
PK Parameter 
The PK parameter analysis population is defined as all 
participants treated who have at least 1 of the PK parameters of 
primary interest. 
PD Parameter 
The PD parameter analysis population is defined as all 
participants treated who have at least 1 of the PD parameters of 
primary interest. 
Safety 
All participants assigned to study intervention and who take at 
least 1 dose of study intervention. Participants will be analyzed 
according to the product they actually received. 
 
9.3. Statistical Analyses 
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. 
9.3.1. Safety Analyses 
Vital signs, AEs and safety laboratory data will be reviewed and summarized on an ongoing 
basis during the study to evaluate the safety of participants. Safety data will be presented in 
tabular and/or graphical format and summarized descriptively, where appropriate. 
9.3.2. Pharmacokinetic Analyses 
PK parameters will be derived from the concentration time profiles using noncompartmental 
methods as data permit. The various PK parameters to be assessed in this study, their 
definition, and method of determination are outlined in Table 1. In all cases, actual PK 
sampling times will be used in the derivation of PK parameters. 
 
Table 1. 
Definitions of PK Parameters 
 
Parameter 
Definition 
Method of Determination 
AUC24 
Area under the plasma concentration time 
profile over the dosing interval 24 hrs, at 
steady-state 
Linear-log trapezoidal method 
Cmax 
Maximum plasma concentration 
Observed directly from the data 
Tmax 
Time for Cmax 
Observed directly from the data as time of first 
occurrence 


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Table 1. 
Definitions of PK Parameters 
 
Parameter 
Definition 
Method of Determination 
t½ 
Terminal elimination half-life 
Loge(2)/kel 
Only those data points judged to describe the 
terminal log-linear decline will be used in the 
regression. 
CL/F 
Apparent clearance after oral dose 
Dose/AUC24 after oral dose 
VZ/F 
Apparent volume of distribution after oral 
dose 
Dose/(AUC24*kel) after oral dose 
• The plasma PK parameters in Table 1 will be summarized descriptively, as 
applicable, in accordance with Pfizer data standards. Individual participant and 
median profiles of the plasma concentration-time data will be plotted using actual and 
nominal times, respectively. Median profiles will be presented on both linear-linear 
and log-linear scales. Plasma concentrations will be listed and summarized 
descriptively by nominal PK sampling time. 
9.3.3. Pharmacodynamic Analyses 
All of the PD endpoints will be summarized by time point and change from baseline for these 
endpoints will also be summarized at specific time points as reported in the SoA. 
9.3.4. Taste Assessment Analyses 
Taste acceptability data will be listed and summarized descriptively (frequencies and 
percentages). 
9.4. Interim Analyses 
No formal interim analysis will be conducted for this study. However, as this is an open- 
label study, the sponsor may conduct unblinded reviews of the data during the course of the 
study for the purpose of safety assessment, facilitating PK modeling for pediatric dose 
decisions and/or supporting clinical development. 
9.5. Sample Size Determination 
A sample size of 12 participants was selected based on practical considerations and should 
provide adequate PK information.37,38 


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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines; 
• Applicable ICH GCP guidelines; 
• Applicable laws and regulations, including applicable privacy laws. 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents (eg, 
advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC by 
the investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC; 
• Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures; 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies, European Medical Device Regulation 2017/745 for 
clinical device research, 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. 


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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of. 
10.1.2. Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. Informed Consent/Assent Process 
The investigator or their representative will explain the nature of the study to the 
participant and their parent(s)/legal guardian and answer all questions regarding the 
study. The participant and their parent(s)/legal guardian should be given sufficient time and 
opportunity to ask questions and to decide whether or not to participate in the trial. 
When consent is obtained from a participant’s parent(s)/legal guardian, the participant’s 
assent (affirmative agreement) must be subsequently obtained when the participant has the 
capacity to provide assent, as determined by the IRB/EC. If the investigator determines that a 
participant’s decisional capacity is so limited they cannot reasonably be consulted, then, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
participant’s assent may be waived with source documentation of the reason assent was not 
obtained. If the study participant does not provide their own assent, the source documents 
must record why the participant did not provide assent (for example, the child is not of 
assenting age per local regulations or policies), how the investigator determined that the 
person signing the consent was the participant’s parent(s)/legal guardian, the consent signer’s 
relationship to the study participant, and that the participant’s assent was obtained or 
waived. If assent is obtained verbally, it must be documented in the source documents. 
If study participants are minors who reach the age of majority or if a child reaches the age of 
assent (per local IRB/EC requirements) during the study, as recognized under local law, the 
child or adolescent must then provide the appropriate assent or consent to document their 
willingness to continue in the study. For an adolescent who reaches the age of consent, 
parental consent would no longer be valid. If the enrollment of emancipated minors is 
permitted by the IRB/EC and local law, the participant must provide documentation of legal 
status to give consent without the permission of a legally authorized representative. 
Participants and their parent(s)/legal guardian must be informed that their participation is 
voluntary. The Participant’s parent(s)/legal guardian will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, HIPAA requirements, where applicable, and the IRB/EC or study center. 
The investigator must ensure that each study participant’s parent(s)/legal guardian and the 
study participant as applicable are fully informed about the nature and objectives of the 


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study, the sharing of data related to the study, and possible risks associated with 
participation, including the risks associated with the processing of the participant’s personal 
data. 
The participant’s parent(s)/legal guardian must be informed that the participant’s personal 
study-related data will be used by the sponsor in accordance with local data protection 
law. The level of disclosure must also be explained to the participant’s parent(s)/legal 
guardian. 
The participant’s parent(s)/legal guardian must be informed that the participant’s medical 
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities. 
The investigator further must ensure that each study participant’s parent(s)/legal guardian is 
fully informed about their right to access and correct their child’s personal data and to 
withdraw consent for the processing of their child’s personal data, keeping in mind the 
privacy rights that may restrict access of older adolescents’ medical records by their 
parent(s)/legal guardian in certain regions. 
The source documentation must include a statement that written informed consent and as 
applicable, assent, was obtained before the participant was enrolled in the study and the date 
the written consent/assent was obtained. The authorized person obtaining the informed 
consent must also sign the ICD. 
Parent(s)/legal guardian and the participant must be reconsented to the most current version 
of the ICD(s)/assent during their participation in the study. 
A copy of the ICD(s) and assent, if written, must be provided to the parent(s)/legal 
guardian and the participant. 
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 90 days from the previous ICD signature date. 
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. 


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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 their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws. 
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
The sponsor maintains standard operating procedures on how to respond in the event of 
unauthorized access, use, or disclosure of sponsor information or systems. 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
This study will use an E-DMC. The E-DMC is independent of the study team and includes 
only external members. The /E-DMC charter describes the role of the E-DMC in more detail. 
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by the E-DMC will be forwarded 
to the appropriate authorized Pfizer personnel for review and final decision. Pfizer will 
communicate such decisions, which may include summaries of aggregate analyses of 
endpoint events and of safety data that are not endpoints, to regulatory authorities and 
investigators, as appropriate. 
10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov 
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer 
sponsored- interventional studies (conducted in patients) that evaluate the safety and/or 
efficacy of a product, regardless of the geographical location in which the study is conducted. 


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These results are submitted for posting in accordance with the format and timelines set forth 
by US law. 
EudraCT/CTIS 
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer sponsored- interventional 
studies in accordance with the format and timelines set forth by EU requirements. 
www.pfizer.com 
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized. 
Documents within marketing applications 
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized. 
Data sharing 
Pfizer provides researchers secure access to participant level data or full CSRs for the 
purposes of “bonafide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Participant- -level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized. 
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
10.1.7. Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document. 


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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, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained. 
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems. 
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
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. 
10.1.8. Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site. 


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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 and its origin can be found in the Clinical 
Monitoring Plan, Source Document Locator, which is maintained by the sponsor. 
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The sponsor or designee will perform monitoring 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 guidelines, and all applicable regulatory requirements. 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. 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 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 the ICH GCP 
guidelines; 
• Inadequate recruitment of participants by the investigator; 


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• Discontinuation of further study intervention development. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights. 
10.1.10. Sponsor’s Medically Qualified Individual 
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the supporting study documentation/study portal or other electronic 
system. 
To facilitate access to their investigator and the sponsor’s MQI for study related- medical 
questions or problems from non-study healthcare professionals, participants are provided 
with an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol 
and study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week. 
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. 


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10.2. Appendix 2: Clinical Laboratory Tests 
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues. 
 
Table 2. 
Protocol-Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
Platelet count 
WBC count 
Total neutrophils 
(Abs) 
Eosinophils (Abs) 
Monocytes (Abs) 
Basophils (Abs) 
Lymphocytes 
(Abs) 
Urea and creatinine 
eCrCl 
Glucose (fasting) 
Sodium 
Potassium 
Chloride 
AST, ALT 
Total bilirubin 
Alkaline phosphatase 
Albumin 
Total protein 
Local dipstick: 
pH 
Glucose (qual) 
Protein (qual) 
Albuminuria (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte esterase 
At screening: 
Serum Pregnancy test 
(β-hCG) 
IP-10 
QFT 
HIV 
Hepatitis B and C 
At Day 1 and Day 7: 
Urine pregnancy test 
 
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. 


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting 
10.3.1. Definition of AE 
 
AE Definition 
• 
 An AE is any untoward medical occunence in a patient or clinical study 
paiiicipant, 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 
abno1mal laborato1y finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
 
 
Events Meeting the AE Definition 
• 
 Any abno1mal laborato1y test results (hematology, clinical chemistiy, 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 abno1mal laborato1y 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 diug tl'eatment, or other therapy. 
• 
 Exacerbation of a chronic or intennittent preexisting condition, including an 
increase in either frequency and/or intensity of the condition. 
• 
New condition detected or diagnosed after study intervention adininistration, even 
though it may have been present before the staii of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected diug-di·ug 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 repo1ied as 
an AE or SAE unless it is an intentional overdose taken with possible suicidaVself­ 
haiming intent. Such overdoses should be repo1ied regardless of sequelae. 


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Events NOT Meeting the AE Definition 
• 
 Any clinically significant abnonnal laborato1y findings or other abnonnal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the paiiicipant'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 
paiiicipant's condition. 
• 
 Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
 Situations in which an untowai·d medical occunence 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 sta1i of the study that do not worsen. 
10.3.2. Definition of an SAE 
 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below: 
a. Results in death 
b. Is life-threatening 
The te1m "life-threatening" in the definition of "serious" refers to an event in which the 
paiiicipant 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 admitted (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 ai·e AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether "hospitalization" occmTed or was necessaiy, the 
AE should be considered serious. 
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE. 


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d. Results in persistent or significant disability/incapacity 
• The te1m disability means a substantial dismption of a person's ability to conduct 
n01mal life functions. 
•  This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, dianhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent eve1yday life functions but do not constitute a substantial dismption. 
e.  Is a congenital anomaly/birth defect 
f.  Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or nonpathogenic 
The event may be suspected from clinical symptoms or laborato1y findings indicating 
an infection in a paiiicipant exposed to a Pfizer product. The te1ms "suspected 
transmission" and "transmission" ai·e considered synonymous. These cases ai·e 
considered unexpected and handled as serious expedited cases by phaimacovigilance 
personnel. Such cases ai·e also considered for repo1iing as product defects, if 
appropriate. 
g. Other situations: 
• Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE repo1iing is appropriate in other situations, such as significant 
medical events that may jeopardize the pa1iicipant 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 dmg 
dependency or diug abuse. 
 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
 
AE and SAE Recording/Reporting 
The table below summarizes the requirements for recording AEs on the CRF and for 
repo1iing SAEs on the CT SAE Repo1i Fo1m to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during pregnancy 
or breastfeeding, and occupational exposure. 


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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. 
* 
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using the CT SAE Report Form and EDP Supplemental Form; if the EDP is associated with an 
SAE, then the SAE is reported to Pfizer Safety using the CT SAE Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form, which would also include details 
of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 
• When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event. 
• The investigator will then record all relevant AE or SAE information in the CRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or SAE CRF page. 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
SAE 
All 
All 
Nonserious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding 
All AEs or SAEs associated 
with EDP or EDB 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF 
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)* 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)** 
Environmental or 
occupational exposure to 
the product under study to 
a nonparticipant (not 
involving EDP or EDB) 
None. Exposure to a study 
nonparticipant is not 
collected on the CRF 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported*** 


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• 
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 paiiicipant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 
• 
 The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical info1mation. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE or SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE repo1ied 
during the study and assign it to 1 of the following categories: 
• 
Mild: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual ADL. 
• 
Moderate: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual ADL, causing discomfo1i, 
but poses no significant or pennanent risk ofhann to the research paiiicipant. 
• 
 Severe: A type of AE that intenupts usual ADL, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
An event is defined as "serious" when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occunence of each AE or SAE. The investigator will use clinical 
judgment to dete1mine the relationship. 
• 
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 rnled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 


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• 
The investigator will also consult the IB and/or product infonnation, for marketed 
products, in their assessment. 
• 
For each AE or SAE, the investigator must document in the medical notes that they 
have reviewed the AE or SAE and have provided an assessment of causality. 
• 
There may be situations in which an SAE has occmTed and the investigator has 
minimal info1mation to include in the initial repo1i 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 their opinion of causality in light of followup 
info1mation and send an SAE followup repo1i with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when detennining regulato1y 
repo1iing 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 repo1iing 
pmposes, as defined by the sponsor. In addition, if the investigator detennines 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 Repo1i Fo1m and in accordance 
with the SAE repo1iing requirements. 
 
 
Follow-Up of AEs and SAEs 
• 
 The investigator is obligated to perfonn or aiTange 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 laborato1y tests or investigations, 
histopathological exaininations, or consultation with other healthcare providers. 
• 
If a paiiicipant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmo1iem findings, including histopathology 
• 
New or updated infonnation will be recorded in the originally submitted 
documents. 
• 
The investigator will subinit any updated SAE data to the sponsor within 24 hours 
of receipt of the info1mation. 


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10.3.4. Reporting of SAEs 
 
SAE Reporting to Pfizer Safety via an Electronic DCT 
• 
The primaiy mechanism for reporting an SAE to Pfizer Safety will be the 
electronic DCT. 
• 
If the electronic system is unavailable, then the site will use the paper SAE DCT 
(see next section) to repo1t the event within 24 hours. 
• 
The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or 
paper fonn (as applicable) as soon as the data become available. 
• 
 After the study is completed at a given site, the electronic DCT will be taken 
offline to prevent the entiy of new data or changes to existing data.. 
• 
If a site receives a report of a new SAE from a study paiticipant or receives updated 
data on a previously repo1ted SAE after the electi·onic DCT has been taken offline, 
then the site can repo1t this infonnation on a paper SAE fonn (see next section) or 
to Pfizer Safety by telephone. 
 
 
SAE Reporting to Pfizer Safety via the CT SAE Report Form 
• 
Facsimile ti-ansmission of the CT SAE Repo1t Fo1m is the prefened method to 
ti·ansinit this infonnation to Pfizer Safety. 
• 
 In circumstances when the facsimile is not working, an alternative method should 
be used, eg, secured (Transpo1t Layer Security) or password-protected email. If 
none of these methods can be used, notification by telephone is acceptable with a 
copy of the CT SAE Repo1t Fo1m 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 Repo1t Fo1m pages within the designated repo1ting 
time frames. 


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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria 
 
Male participants are not required to use contraception in this study, because ritlecitinib is 
not likely to transfer to a partner through semen at pharmacologically relevant blood levels. 
 
For EU/UK only: 
 
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 30 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 
 
• Refrain from donating sperm. 
PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent. 
OR 
• Must agree to use contraception/barrier as detailed below: 
• Agree to use a male condom, and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception as a condom may 
break or leak when having sexual intercourse with a WOCBP who is not currently 
pregnant. 
10.4.2. Female Participant Reproductive Inclusion Criteria 
The criteria below are part of inclusion criterion 1 (Age and Sex; Section 5.1) and specify the 
reproductive requirements for including female participants. Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
• 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 definition in Section 10.4.3). 
OR 
• Is a WOCBP and agrees to use a highly effective contraceptive method (failure rate of 
<1% per year) with low user dependency during the intervention period and for at 
least 30 days after the last dose of study intervention, which corresponds to the time 
needed to eliminate any reproductive safety risk of the study intervention(s). The 


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investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention. 
OR 
• Is a WOCBP and agrees to use a highly effective (failure rate of <1% per year) user- 
dependent method of contraception during the intervention period and for at least 30 
days after the last dose of study intervention, which corresponds to the time needed to 
eliminate any reproductive safety risk of the study intervention(s). In addition to her 
use of the highly effective method above, she agrees to concurrently use an effective 
barrier method. The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention. 
The investigator is responsible for reviewing the woman’s medical history, menstrual history, 
and recent sexual activity in order to decrease the risk of enrolling a woman with an early 
undetected pregnancy. 
If a female participant becomes pregnant during study participation, this information will be 
shared with her parents/legal guardians. 
Notification of parents/legal guardians must comply with local regulations. 
10.4.3. Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP: 
1. Premenarchal. 
2. Premenopausal female with 1 of the following:. 
• Documented hysterectomy; 
• Documented bilateral salpingectomy; 
• Documented bilateral oophorectomy. 
For individuals with permanent infertility due to a medical cause other than the above (eg, 
mullerian agenesis, androgen insensitivity), investigator discretion should be applied to 
determining study entry. 


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Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study. 
3. Postmenopausal female: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition: 
• A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 
• A female on HRT and whose menopausal status is in doubt will be required to use 
one of the highly effective nonestrogen hormonal contraception methods if she 
wishes to continue her HRT during the study. Otherwise, she 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. 
The following contraceptive methods are appropriate for this study: 
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation. 
2. Intrauterine device. 
3. Intrauterine hormone releasing system. 
4. Bilateral tubal occlusion. 
5. Vasectomized partner. 
• Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the 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. 


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Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: 
• Oral + barrier* 
• Intravaginal + barrier* 
• Transdermal + barrier* 
7. Progestogen-only hormone contraception associated with inhibition of ovulation: 
• Oral + barrier* 
• Injectable + barrier* 
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. 
* Acceptable barrier methods to be used concomitantly with options 6 or 7 for the study 
include any of the following: 
• Male or female condom, with or without spermicide (male condom and female 
condoms should not be used together due to risk of failure with friction); 
• Cervical cap, diaphragm, or sponge with spermicide. 
• A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods). 


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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments 
Potential Cases of Drug-Induced Liver Injury 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.” 
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations (>2 × 
ULN) by several days or weeks. The increase in T bili typically occurs while AST/ALT is/are 
still elevated above 3 × ULN (ie, AST/ALT and T bili values will be elevated within the same 
laboratory sample). In rare instances, by the time T bili 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 T bili 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 T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili 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 T bili 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 T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller). 
Rises in AST/ALT and T bili 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.. 


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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 T bili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 


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10.6. Appendix 6: Kidney Safety Monitoring Guidelines 
10.6.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury 
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum 
creatinine (Scr measurement to estimate creatinine clearance normalized to BSA [Modified 
Schwartz eCrCl]). 
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care. 
10.6.2. Age-Specific Kidney Function Calculation Recommendation 
Modified Schwartz equation (pediatric patients 2 to <12 years of age). 
• CrCl (mL/min/1.73 m2) = (K*Ht)/Scr 
• Height (Ht) in cm; serum creatinine (Scr) in mg/dl 
• K (proportionally constant): 
• Female child: K = 0.55 
• Male child: K = 0.70 
10.6.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities 
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to 
KDIGO criteria. 


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10.7. Appendix 7: Prohibited Concomitant Medications That May Result in DDI 
This is not an all-inclusive list. This list of drugs prohibited for potential DDI concerns with 
the IP may be revised during the course of the study with written notification from sponsor, 
to include or exclude specific drugs or drug categories for various reasons (eg, emerging DDI 
results for the IP, availability of new information in literature on the DDI potential of other 
drugs). 
Study personnel should stay current and consult with their pharmacy to exclude all 
concomitant medications that are moderate to potent CYP3A inducers or sensitive or 
moderate sensitive CYP3A substrates or sensitive or moderate sensitive CYP1A2 substrates. 
If a medication is a sensitive or moderate sensitive CYP3A substrate, or a sensitive or 
moderate sensitive CYP1A2 substrate, and is not listed in Table 3 and Table 4 as prohibited 
or permitted, consultation with the Sponsor is required. 
 
Table 3. 
Prohibited Concomitant CYP3A Inducers and Substrates 
 
Sensitive CYP3A Substratesa 
Moderate Sensitive CYP3A 
Substratesb 
Moderate to Potent CYP3A 
Inducersc 
Dasatinib 
Aprepitant 
Avasimibed 
Dronedarone 
Eliglustat 
Bosentan 
Ebastine 
Pimozide 
Barbiturates 
Lomitapide 
Rilpivirine 
Carbamazepined 
Nisoldipine 
Efavirenz 
Sirolimus 
Etravirine 
Tacrolimus 
Mitotaned 
Tolvaptan 
Modafinil 
Nafcillin 
Phenobarbitald 
Phenytoind 
Rifabutind 
Rifampind 
St. John’s Wortd 
Talviraline 
a. 
Sensitive CYP3A substrates are drugs that demonstrate an increase in AUC of ≥5-fold with strong 
index inhibitors of a given metabolic pathway in clinical DDI studies. 
b. Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold. 
c. 
All prohibited drugs that are CYP3A inducers require at least a 28 day or 5 half-lives (whichever is 
longer) washout prior to the first dose of study intervention. In a situation where appropriate medical 
care of a participant requires the use of a prohibited CYP3A inducer: Moderate to potent inducers of 
CYP3A are not permitted in the study EXCEPT in emergency situations. Note: Mitotane is not 
permitted for any duration due to its long half-life; however, if necessary mitotane may be used in an 
emergency, however the participant will then be discontinued from the study. Topical (including skin or 
mucous membranes) application of antimicrobial and antifungal medications is permitted. 
d. Notated as potent inducers. 


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Table 4. 
Prohibited Concomitant CYP1A2 Substrates 
 
Sensitive CYP1A2 Substrates 
Moderate Sensitive CYP1A2 Substrates 
Tizanidine 
Pirfenidone 
Roflumilast 
Sensitive substrates are drugs that demonstrate an increase in AUC of ≥5 fold with strong index 
inhibitors of a given metabolic pathway in clinical DDI studies. Topical (including skin or mucous 
membranes) application of antimicrobial and antifungal medications is permitted. 
Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5 fold. 
Investigators should consult the product label for any other medication used during the study 
for information regarding medication that is prohibited for concomitant use. 


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10.8. Appendix 8: Country-Specific Requirements 
10.8.1. France 
Contrat Unique 
1. GCP Training 
Before enrolling any participants, the investigator and any sub-investigators will 
complete the Pfizer-provided Good Clinical Practice training course (“Pfizer GCP 
Training”) or training deemed equivalent by Pfizer. Any investigators who later join 
the study will do the same before performing study-related duties. For studies of 
applicable duration, the investigator and sub-investigators will complete Pfizer GCP 
Training or equivalent every 3 years during the term of the study, or more often if 
there are significant changes to the ICH GCP guidelines or course materials. 
2. Study Intervention 
No participants or third-party payers will be charged for study intervention. 
3. Urgent Safety Measures 
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. 
4. Termination Rights 
Pfizer retains the right to discontinue development of ritlecitinib at any time. 
10.8.2. Japan 
10.8.2.1. Reporting Requirements 
When becoming aware of any defect in an investigational product that meets the following 
conditions, the investigator must report it to the clinical trial sponsor within 24 hours (see 
Section 10.8.2.2). Note: Such reporting of a defect in an investigational product does not alter 
the AE reporting process described in Appendix 3. 
• A defect that, directly or indirectly, resulted in an SAE (see Section 10.3.2) observed 
in a study participant, user, or other person 
OR 
• A defect related to an investigational product whose recurrence might lead to death or 
serious deterioration in health 


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For reporting of complaints concerning quality of investigational products not meeting the 
reporting requirements above, see the detailed procedure in the “Complaints concerning 
investigational products” section of the IPM. 
10.8.2.2. Reporting Procedure 
The procedure for reporting of defects in study interventions to the sponsor should be agreed 
upon in advance for each study by the Safety Department and the Study Team in 
Development Japan and described in this section. 


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10.9. Appendix 9: Hepatitis B testing algorithm and full eligibility criteria 
 
For participants in countries in which hepatitis B prevalence has been reported at a 
rate of >5.0%* or if required by local standard of care, participants will be tested as 
follows: 
 
At screening, HBsAg and HBcAb will be tested: 
a. If both tests are negative, the participant is eligible for study inclusion. 
b. If HBsAg is positive, the participant must be excluded from participation in the study. 
c. If HBsAg is negative and HBcAb is positive, HBsAb and HBVDNA reflex testing is 
required: 
• If HBsAb is negative, the participant must be excluded from participation in the 
study; 
• If HBVDNA is detected, the participant must be excluded from participation in the 
study; 
• If HBsAb is positive and HBVDNA is undetectable, the participant is eligible for 
study inclusion. 
In all other countries, participants will be tested as follows: 
At screening, HBsAg and HBcAb will be tested: 
 
a. If both tests are negative, the participant is eligible for study inclusion. 
b. If HBsAg is positive, the participant must be excluded from participation in the 
study. 
c. If HBsAg is negative and HBcAb is positive, HBsAb reflex testing is required: 
• If HBsAb is negative, the participant must be excluded from participation in the 
study; 
• If HBsAb is positive, the participant is eligible for study inclusion. If the participant is 
included in the study, for subsequent visits no hepatitis B testing is required. 


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10.10. Appendix 10 – SALT 
Diagnosis of AA must be performed by a qualified dermatologist (board certified or 
equivalent) who has experience with AA. 
SALT is a quantitative assessment of alopecia severity based on scalp terminal hair loss. 
Score parameters utilize a visual aid showing the division of the scalp hair into four 
quadrants (back, top of scalp, and both sides), with each of the four quadrants given an 
accurate determination of the % of scalp surface area covered, representing 24%, 40%, 18%, 
and 18% of the total scalp surface area, respectively. 
The overall SALT score will be collected at the Screening Visit, for eligibility purposes. 
The assessment will be performed by a qualified dermatologist (board certified or equivalent) 
who has experience with AA or a delegated member of the study staff (an experienced and 
qualified physician or healthcare professional). 


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10.11. Appendix 11 – C-SSRS 
Suicidal Ideation and Behavior will be assessed at Screening using the C-SSRS (Columbia 
Suicide Severity Rating Scale – pediatric version, baseline assessment) version for pediatric 
patients 6 to 11 years old. 
There are 2 versions of the C-SSRS - “C-SSRS for screening and baseline visits” and “C- 
SSRS for any post-baseline visits”. In this study, only the baseline version will be used, for 
eligibility purposes. 
The person conducting the assessment must be either: 
a. A Mental Health Professional or 
b. A study staff member with appropriate training and certification (Completion of 
training curriculum as required by the Columbia Lighthouse Project) 
Participants who had previous history of suicidal behaviors in the past 5 years (“Yes” answer 
for events that occurred in the past 5 years) to any of the suicidal behavior items of the 
C-SSRS or any lifetime history of serious or recurrent suicidal behavior, a risk assessment 
must be performed and documented by a qualified mental health professional to assess 
whether it is safe for the participant to participate in the trial. 


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10.12. Appendix 12 – CDRS-R 
The CDRS-R is a brief 17-item rating scale for diagnosing depression and assessing its 
severity. The scale is designed for use in 6- to 12-year-old children. Individuals are rated on 
seventeen symptom areas, including dysfunction relating to schoolwork, interpersonal 
relationships, psychosomatic complaints, and other thoughts and feelings commonly 
presenting in depressed children and adolescents. Scores are determined by a clinician 
through a semi-structured interview with the child and parent.39 Interviews take about 10-15 
minutes to complete and score. Each item score ranges from 1 to 5 or 1 to 7. Possible total 
scores ranging from 17 to 113. 


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10.13. Appendix 13.1 – PROMIS® Parent Proxy Short Form v2.0 – Anxiety 8a 
The PROMIS Parent Proxy Short Form v2.0 – Anxiety 8a is an 8-item measure of anxiety. 
Each item has five response options ranging in value from 1 to 5. Raw scores are calculated 
by summing the values of the response to each question. The lowest possible raw score for 
this measure is 8 and the highest possible raw score is 40. Raw scores are transformed to 
T-scores using a conversion table available from the developer.40 
T-score rescales the raw score into a standardized score with a mean of 50 and a SD of 10. 
Therefore, a person with a T-score of 60 is one SD above the pediatric population mean, and 
a T-Score of 70 is two SDs above the pediatric population mean of 50. PROMIS T-scores 70 
or greater are considered severe dysfunction; T-scores from 60 to 69 are considered moderate 
dysfunction (PROMIS 2020a).40 
10.13.1. Appendix 13.2 – PROMIS® Parent Proxy Short Form v2.0 – Depressive 
Symptoms 6a 
The PROMIS Parent Proxy Short Form v2.0 – Depressive Symptoms 6a is a 6-item measure 
of depressive symptoms. Each item has five response options ranging in value from 1 to 5. 
Raw scores are calculated by summing the values of the response to each question. The 
lowest possible raw score for this measure is 6 and the highest possible raw score is 40. Raw 
scores are transformed to T-scores using a conversion table available from the developer. 40 
T-score rescales the raw score into a standardized score with a mean of 50 and a SD of 10. 
Therefore, a person with a T-score of 60 is one SD above the pediatric population mean, and 
a T-Score of 70 is two SDs above the pediatric population mean of 50. PROMIS T-scores 70 
or greater are considered severe dysfunction; T-scores from 60 to 69 are considered moderate 
dysfunction (PROMIS 2020a). 40 


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10.14. Appendix 14 - BRIEF®2 
The BRIEF®2, that will be used in this study is an ObsRO parent/caregiver completed scale 
designed to assess executive behaviors in children and adolescents. The BRIEF®2 evaluates 
neuropsychological development and executive functions in adolescents. The BRIEF®2 
scales assess how well the child is demonstrating behavioral or emotional control, initiating 
activity, engaging in planful and well-organized problem solving, and monitoring one’s own 
social success and problem-solving outcomes. 
The BRIEF®2 consists of 63 items and yields scores on nine scales, with the Inhibit and 
Self-Monitor scales comprising the BRI, the Shift and Emotional Control scales comprising 
the ERI, and the Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization 
of Materials scales comprising the CRI. The questionnaire will be completed by the 
parent/caregiver of the participant.41 


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10.15. Appendix 15 - Modified CDLQI 
The CDLQI is a children’s version of the DLQI.42 The CDLQI consist of 10 items that assess 
participant health related quality of life (daily activities, personal relationships, symptoms 
and feelings, leisure, work and school, and treatment). The CDLQI assesses quality of life 
over the last week. In this modified version, all items were modified to refer to “alopecia 
areata” instead of “skin” or “skin trouble”. 
 
Each item is scored from 0 to 3. Questions left unanswered are given a score of 0. Item 
scores are summed and expressed as usual out of a maximum score of 30. 
The questionnaires are self-explanatory and can be handed to the participant who is asked to 
fill them in with the help of the child’s parent or guardian, as necessary. 


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10.16. Appendix 16 - WISC-V 
The WISC-V is clinical measure of cognitive ability/intelligence of children 6 to 16 years of 
age. Responses from the WISC-V can be used to calculate scores for intellectual functioning 
in several cognitive domains, as well as a composite score that represents the general 
intellectual ability. 
The WISC-V is composed of multiple subtests and index scales, with each subtests grouped 
into three general categories of index scales: primary, ancillary, and complementary. 
Administration of the primary subtests is recommended for a comprehensive description of 
intellectual ability. The ancillary and complementary subtests can be administered in addition 
to the primary subtests to provide a broader sampling of intellectual functioning and to yield 
more information. 
This assessment will be administered by the principal investigator or a delegated member of 
the study staff. Administration and Scoring Manual, Technical and Interpretive Manual will 
be provided to the sites.43 


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10.17. Appendix 17: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
A1 to A3 
albuminuria (KDIGO albuminuria severity standardization) 
AA 
alopecia areata 
Abs 
absolute 
ADL 
activity/activities of daily living 
AE 
adverse event 
AESI 
adverse event of special interest 
AKI 
acute kidney injury 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AT 
alopecia totalis 
AU 
alopecia universalis 
AUC 
Area under the concentration-time curve 
AUCtau 
area under the concentration-time curve from time zero to the end of 
the dosing interval 
AxMP 
auxiliary medicinal product 
BID 
twice daily 
BP 
blood pressure 
BRI 
Behavior Regulation Index 
BRIEF 
Behavior Rating Inventory of Executive Function 
CDLQI 
Children's Dermatology Life Quality Index 
CDRS-R 
Childhood Depression Rating Scale – Revised 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CMV 
cytomegalovirus 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRI 
Cognitive Regulation Index 
CRO 
contract research organization 
CSR 
Clinical Study Report 
C-SSRS 
Columbia – Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTIS 
Clinical Trial Information System 
CVEAC 
Cardiovascular Event Adjudication Committee 
CYP 
cytochrome P450 
CYP1A2 
cytochrome P450 family 1 subfamily A member 2 
CYP3A 
cytochrome P450 family 3 subfamily A 
DCT 
data collection tool 
DDI 
drug-drug interaction 
DILI 
drug-induced liver injury 


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Abbreviation 
Term 
EBV 
Epstein Barr Virus 
EC 
ethics committee 
ECC 
emergency contact card 
ECG 
electrocardiogram or electrocardiography 
eCrCl 
estimated creatinine clearance 
eCRF 
electronic case report form 
EDB 
exposure during breastfeeding 
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 
ERI 
Emotion Regulation Index 
eSAE 
electronic serious adverse event 
EU 
European Union 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database) 
FACS 
Fluorescence-Activated Cell Sorting 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
F/U 
follow-up 
G1 to G5 
Grade (KDIGO eGFR category standardization) 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBVDNA 
Hepatitis B Virus Deoxyribonucleic acid 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HR 
heart rate 
HRQoL 
health-related quality of life 
HRT 
hormone replacement therapy 
Ht 
height 
IB 
Investigator’s Brochure 
ICD 
informed consent document 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ID 
identification 
IFN 
interferon 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 


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Abbreviation 
Term 
INR 
international normalized ratio 
IP 
investigational product 
IP-10 
induced protein 10 
IPAL 
Investigational Product Accountability Log 
IPM 
investigational product manual 
iPSP 
initial pediatric study plan 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
JAK 
Janus kinase 
K 
Proportionality constant for Bedside and Modified Schwartz 
Equations (kidney function) 
K2EDTA 
Dipotassium ethylenediaminetetraacetic acid 
KDIGO 
Kidney Disease: Improving Global Outcomes 
LFT 
liver function test 
LPD 
local product document 
MAC 
Malignancy Adjudication Committee 
MMF 
mycophenolate mofetil 
MQI 
medically qualified individual 
MRHD 
maximum recommended human dose 
MTX 
methotrexate 
NA 
not applicable 
NIMP 
noninvestigational medicinal product 
NK 
natural killer 
NSEAC 
Neurosafety Event Adjudication Committee 
ObsRO 
observer-reported outcomes 
OIRC 
Opportunistic Infection Review Committee 
PD 
pharmacodynamic(s) 
PGI-C 
Patient’s global impression of change 
PI 
principal investigator 
PIP 
Pediatric Investigational Plan 
PK 
pharmacokinetic(s) 
PR 
pulse rate 
PSSA 
Pfizer's Serious Adverse Event Submission Assistant 
PT 
prothrombin time 
QD 
once daily 
QFT 
QuantiFERON test 
QoL 
quality of life 
qual 
qualitative 
RBC 
red blood cell 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SALT 
Severity of Alopecia Tool 
SAP 
Statistical Analysis Plan 


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Abbreviation 
Term 
SC 
subcutaneous(ly) 
Scr 
serum creatinine 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SRSD 
Single Reference Safety Document 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
tuberculosis 
T bili 
total bilirubin 
TBV 
total blood volume 
TEAE 
Treatment emergent adverse event 
TH1 
type 1 helper T cell 
TOC 
table of contents 
UK 
United Kingdom 
ULN 
upper limit of normal 
US 
United States 
UTI 
urinary tract infection 
WBC 
white blood cell 
WHO 
World Health Organization 
WISC-V 
Wechsler Intelligence Scale for Children - 5th edition 
WOCBP 
woman/women of childbearing potential 


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11. REFERENCES 
 
 
 
1 
Hordinsky M, Donati A. Alopecia areata: an evidence-based treatment update. Am J 
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2 
Hordinsky MK. Current Treatments for Alopecia Areata. J Investig Dermatol Symp. 
2015;17(2):44–6. 
3 
Messenger AG, McKillop J, Farrant P, et al. British Association of Dermatologists' 
guidelines for the management of alopecia areata 2012. Br J Dermatol. 
2012;166(5):916–26. 
4 
Alkhalifah A, Alsantali A, Wang E, et al. Alopecia areata update: part II – treatment. 
J Am Acad Dermatol. 2010;62(2):191–204. 
5 
Delamere FM, Sladden MJ, Dobbins HM, et al. Interventions for alopecia areata. 
Cochrane Database Syst Rev. 2008;(2):CD004413. 
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Crispin MK, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor 
tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. 
7 
Kassira S, Korta DZ, Chapman LW, et al. Review of treatment for alopecia totalis and 
alopecia universalis. Int J Dermatol. 2017;56(8):801–10. 
8 
Liu LY, Craiglow BG, Dai F, et al. Tofacitinib for the treatment of severe alopecia 
areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017;76(1):22–8. 
9 
Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med. 2012;366(16):1515–25. 
10 
Hordinsky MK. Overview of alopecia areata. J Investig Dermatol Symp Proc. 2013; 
16(1):S13–5. 
11 
Gilhar A. Collapse of immune privilege in alopecia areata: coincidental or substantial? J 
Invest Dermatol. 2010;130(11):2535–7. 
12 
Bertolini M, Zilio F, Rossi A, et al. Abnormal interactions between perifollicular mast 
cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata. PLoS 
ONE 2014;9(5):e94260. 
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Suárez-Fariñas M, Ungar B, Noda S, et al. (2015). Alopecia areata profiling shows TH1, 
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Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study of 191 
patients. J Am Acad Dermatol. 2006;55:438–41. 
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Trüeb RM, Dias MFRG. Alopecia Areata: a Comprehensive Review of Pathogenesis 
and Management. Clin Rev Allergy Immunol. 2018;54(1):68-87. doi:10.1007/s12016- 
017-8620-9 
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Alkhalifah A. Alopecia areata update. Dermatol Clin 2013;31:93–108. 
18 
Hunt N, McHale S. The psychological impact of alopecia. BMJ. 2005;331(7522):951–3. 
19 
McGarvey EL, Baum LD, Pinkerton RC, et al. Psychological sequelae and alopecia 
among women with cancer. Cancer Pract 2001;9:283–9. 
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Colon EA, Popkin MK, Callies AL, et al. Lifetime prevalence of psychiatric disorders in 
patients with alopecia areata. Comp Psychiatry 1991;32:245–51. 
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Ruiz-Doblado S, Carrizosa A, García-Hernández MJ. Alopecia areata: psychiatric 
comorbidity and adjustment to illness. Int J Dermatol. 2003;42:434–7. 
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Chen W, Mempel M, Traidl-Hofmann C, et al. Gender aspects in skin diseases. J Eur 
Acad Dermatol Venereol. 2010;24:1378–1385. 
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Sellami R, Masmoudi J, Ouali U, et al. The relationship between alopecia areata and 
alexithymia, anxiety and depression: A case-control study. Indian J Dermatol. 
2014;59(4):421. 
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Fricke ACV, Miteva M. Epidemiology and burden of alopecia areata: a systematic 
review. Clin Cosmet Investig Dermatol. 2015; 8:397–403. 
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Liakopoulou M, Alifieraki T, Katideniou A, et al. Children with alopecia areata: 
psychiatric symptomatology and life events. J Am Acad Child Adolesc Psychiatry. 
1997;36(5):678–84. 
26 
Dubois M, Baumstarck-Barrau K, Gaudy-Marqueste C, et al. Quality of life in alopecia 
areata: a study of 60 cases. J Invest Dermatol 2010;130: 2830–3. 
27 
Ghajarzadeh M, Ghiasi M, Kheirkhah S. Associations between skin diseases and quality 
of life: a comparison of psoriasis, vitiligo, and alopecia areata. Acta Medica Iranica. 
2012;50(7):511–5. 


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Masmoudi J, Sellami R, Ouali U, et al. Quality of Life in Alopecia Areata: A Sample of 
Tunisian Patients. Dermatol Res Pract. 2013; 2013:983804. 
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de Hollanda TR, Sodré CT, Brasil MA, et al. Quality of life in alopecia areata: a case- 
control study. Int J Trichology. 2014;6(1):8–12. 
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Baghestani S, Zare S, Seddigh SH. Severity of depression and anxiety in patients with 
alopecia areata in Bandar Abbas, Iran. Dermatol Reports. 2015;7(3):6063. 
31 
Jankovic S, Perić J, Maksimović N, et al. Quality of life in patients with alopecia areata: 
a hospital-based cross-sectional study. J Eur Acad Dermatol Venereol. 
2016;30(5):840-6. 
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Rencz F, Gulácsi L, Péntek M, et al. Alopecia areata and health-related quality of life: a 
systematic review and meta-analysis. Br J Dermatol. 2016;175(3):561–71. 
33  Zhang M, Zhang N. Quality of life assessment in patients with alopecia areata and 
androgenetic alopecia in the People's Republic of China. Patient Prefer Adherence. 
2017;11:151–5. 
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and-emotional-wellness-in-children. Accessed: 14 Mar 2018. 
35  Christensen T, Yang JS, Castelo-Soccio L. Bullying and Quality of Life in Pediatric 
Alopecia Areata. Skin Appendage Disord 2017;3:115–8. 
36  Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and 
variants in adolescents. J Am Acad Dermatol 2017;76:29–32. 
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(CDER); December 2014 Clinical Pharmacology. Available from: 
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(CDRS-R) Children's Depression Rating Scale, Revised. Available from: 
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of the concept being measured. Available at: https://www.healthmeasures.net/score-and- 
interpret/interpret-scores/promis. Accessed: 24 August 2020. 
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Gioia, G.A., Isquith, PK., Guy, S C.,et al. Behavior Rating Inventory of Executive 
Function; 2000. 
42 Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life Quality Index (CDLQI): 
Initial validation and practical use. Br J of Dermatol, 1995; 132: 942-9. 
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Gienger, Claudia Angelika. Wechsler Intelligence Scale for Children – Fifth Edition 
(WISC-V). Verlag Hans Huber; 2018 

SAP_001.pdf: 
Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 1 of 13 
 
 
 
 
 
 
 
Protocol B7981031 
 
 
 
 
An Interventional PK, PD, Phase 1, Open-Label Study to Investigate PK and PD of 
Multiple-Dose Ritlecitinib in Children 6 to Less Than 12 Years of Age with Severe 
Alopecia Areata 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
 
 
 
 
 
Version: 
1 
Date: 
15 Nov 2022 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 2 of 13 
 
 
TABLE OF CONTENTS 
LIST OF TABLES .................................................................................................................... 3 
LIST OF FIGURES ................................................................................................................... 3 
APPENDICES ........................................................................................................................... 3 
1. VERSION HISTORY ........................................................................................................... 4 
2. INTRODUCTION ................................................................................................................. 4 
2.1. Modifications to the Analysis Plan Described in the Protocol ................................. 4 
2.2. Study Objectives and Endpoints ............................................................................... 4 
2.3. Study Design ............................................................................................................. 5 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS .................................................................................................................. 6 
3.1. Primary Endpoint(s) .................................................................................................. 6 
3.2. Secondary Endpoint(s) .............................................................................................. 6 
3.2.1. PK Endpoints ............................................................................................... 6 
3.2.2. PD Endpoints ............................................................................................... 6 
3.2.3. Safety Endpoints .......................................................................................... 6 
3.2.4. Taste Acceptability ....................................................................................... 7 
3.3. Other Endpoint(s) ..................................................................................................... 7 
3.4. Baseline Variables .................................................................................................... 7 
3.5. Safety Endpoints ....................................................................................................... 7 
3.5.1. Adverse Events ............................................................................................ 7 
3.5.2. Vital Signs .................................................................................................... 7 
3.5.3. Laboratory Data ........................................................................................... 7 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)..................................................... 8 
5. GENERAL METHODOLOGY AND CONVENTIONS ..................................................... 8 
5.1. Hypotheses and Decision Rules ............................................................................... 8 
5.2. General Methods ....................................................................................................... 8 
5.2.1. Analyses for Binary Endpoints .................................................................... 8 
5.2.2. Analyses for Continuous Endpoints ............................................................. 8 
5.3. Methods to Manage Missing Data ............................................................................ 9 
5.3.1. Pharmacokinetic Data .................................................................................. 9 
5.3.2. Pharmacodynamic Data.............................................................................. 10 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
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5.3.3. Safety Data .................................................................................................. 10 
6. ANALYSES AND SUMMARIES ....................................................................................... 10 
6.1. Primary Endpoint(s) ................................................................................................. 10 
6.2. Secondary Endpoint(s) ............................................................................................. 10 
6.2.1. PK endpoints ............................................................................................... 10 
6.2.2. PD Endpoints .............................................................................................. 10 
6.2.3. Taste Assessment Analyses ........................................................................ 11 
6.2.4. Safety data ................................................................................................... 11 
6.3. Subset Analyses ....................................................................................................... 11 
6.4. Baseline and Other Summaries and Analyses .......................................................... 11 
6.4.1. Baseline Summaries .................................................................................... 11 
6.4.2. Study Conduct and Participant Disposition ................................................ 11 
6.4.3. Study Treatment Exposure .......................................................................... 11 
6.4.4. Concomitant Medications and Nondrug Treatments .................................. 11 
6.5. Safety Summaries and Analyses .............................................................................. 11 
6.5.1. Adverse Events ........................................................................................... 11 
6.5.2. Laboratory Data .......................................................................................... 12 
6.5.3. Vital Signs ................................................................................................... 12 
7. INTERIM ANALYSES ....................................................................................................... 12 
APPENDICES .......................................................................................................................... 13 
 
LIST OF TABLES 
Table 1. 
Summary of Changes ................................................................................. 4 
Table 2. 
Plasma PF-06651600 PK Parameters and Definitions ............................... 6 
Table 3. 
PK Parameters to be Summarized Descriptively by Treatment ............... 10 
 
 
LIST OF FIGURES 
Figure 1. 
B7981031 Study Schema ............................................................................ 5 
APPENDICES 
Appendix 1. List of Abbreviations ........................................................................................... 13 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 4 of 13 
 
 
NOTE: Italicized text within this document has been taken verbatim from the Protocol. 
1. VERSION HISTORY 
Table 1. 
Summary of Changes 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1/ 
15 Nov 2022 
Original 
03 Oct 2022 
NA 
NA 
2. INTRODUCTION 
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study B7981031. 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. Modifications to the Analysis Plan Described in the Protocol 
None. 
2.2. Study Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To characterize the PK of ritlecitinib in children with 
alopecia areata (AA) 6 to <12 years of age. 
• 
AUC24 on Day 7 
Secondary: 
Secondary: 
• 
To further characterize the PK of ritlecitinib in 
children with AA 6 to <12 years of age. 
• 
Cmax, Tmax, CL/F, VZ/F and t½ on Day 7 
• 
To characterize the PD of ritlecitinib in children with 
AA 6 to <12 years of age. 
• 
Change from baseline in interferon gamma IP-10 and 
lymphocyte subsets (T cell, B cell, and NK cells) on 
Day 7 
• 
To evaluate the safety and tolerability of ritlecitinib in 
children with AA 6 to <12 years of age. 
• TEAE 
• Treatment related AEs. 
• Serious AEs (SAEs) and AEs leading to discontinuation. 
• Clinically significant abnormalities in vital signs. 
• Clinically significant abnormalities in clinical 
laboratory values. 
• 
To assess the overall palatability, acceptability, and 
tolerability of the proposed commercial age 
appropriate formulation in children with AA aged 6 to 
<12 years of age. 
• 
Taste assessment 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
Page 5 of 13 
 
 
-
2.3. Study Design 
This is an interventional, PK, PD, Phase 1, open label study in children 6 to less than 12 
years of age with 50% scalp hair loss due to AA. The pwpose of the study is to collect data 
to support dose selection for subsequent studies in the same population. 
Participants will be screened and, if all eligibility criteria are met, will receive the first dose 
of IP within 28 days after the screening visit. Participants will receive 20 mg ritlecitinib in 
one dose, daily, for 7 consecutive days. On Day 7 (EOT) blood samples for PK will be 
collected at Ohr (pre-dose), 0.5 hr, 1 hr, 3 hrs, and 8 hrs after dosing. At least 12 evaluable 
participants with respect to the primary endpoint will be enrolled in the study. Participants 
that are not able to provide a full set of evaluable PK data or that miss more than one dose 
may be replaced at the discretion of the sponsor. A follow-up visit will be conducted by 
phone, 28 to 35 days after the last dose of ritlecitinib (Refer to Figure 1). 
 
Figure 1. 
B7981031 Study Schema 
 
28 
 
 
 
 
' 
Screening 
C, 
C, 
C, 
C, 
C, 
!:I) 
!:I) 
!:I) 
'< 
'< 
'< 
N 
\.,) 
V, 
0\ 
-..) 
 
 
28-35 Days 
Safety 
 
Foll7 
 
 
 
 
 
 
 
 
 
End of 
i 
Beginning of Treatment 
I 
End of Treatment  I 
 
Visit Types: 
• 
Treatment) or Early Tennination 
 
• 
Telephone visits: Days 2, 4, 6 and End of Study 
 
• 
 
dosing or safety issues 
• 
PK draws: Day 7 (End of Treatment) or Early Tennination at Ohr (pre-dose), 0.5 
hr, 1 hr, 3 hrs, and 8 hrs after dosing. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Office visits: Screening, Day 1 (Beginning of treatment), Day 7 (End of 
C,


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 6 of 13 
 
 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint(s) 
The primary endpoint is Area under the plasma concentration time profile over the dosing 
interval 24 hours, at steady-state (AUC24) of ritlecitinib on Day 7. 
3.2. Secondary Endpoint(s) 
The secondary endpoints are the plasma PK and PD parameters of PF-06651600. 
3.2.1. PK Endpoints 
The PK parameters will be derived (as data permit) from the concentration-time data using 
standard noncompartmental methods of analysis as outlined in Table 2. Actual PK sampling 
times will be used in the derivation of PF-06651600 PK parameters when available. In the 
case that actual PK sampling times are not available, nominal PK sampling time will be used 
in the derivation of PK parameters. 
 
Table 2. 
Plasma PF-06651600 PK Parameters and Definitions 
 
Parameter 
Definition 
Method of Determination 
AUC24 
Area under the plasma 
concentration time profile over 
the dosing interval 24 hrs, at 
steady-state 
Linear-log trapezoidal method 
Cmax 
Maximum plasma concentration 
Observed directly from the data 
Tmax 
Time for Cmax 
Observed directly from the data as time of first 
occurrence 
t½ 
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 loglinear decline will be used in the regression. 
Only those data points judged to describe the terminal 
log-linear decline will be used in the regression. 
CL/F 
Apparent clearance after oral 
dose 
Dose/AUC24 after oral dose 
VZ/F 
Apparent volume of distribution 
after oral dose 
Dose/(AUC24*kel) after oral dose 
3.2.2. PD Endpoints 
The main PD parameters are the change from baseline in interferon gamma IP-10 and 
lymphocyte subsets (T cell, B cell, and NK cells) on Day 7. 
3.2.3. Safety Endpoints 
Safety data are also considered as secondary endpoints and are discussed in Section 3.5. 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
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3.2.4. Taste Acceptability 
Taste acceptability data will be used to assess the overall palatability, acceptability, and 
tolerability of the proposed age appropriate formulation in children with AA aged 6 to <12 
years of age. 
3.3. Other Endpoint(s) 
None. 
3.4. Baseline Variables 
Baseline characteristics will be collected according to the schedule of activities (SoA) as 
specified in the protocol. 
3.5. Safety Endpoints 
The following data are considered in standard safety summaries (see protocol for collection 
days, baseline assessment, and list of parameters): 
• Adverse Events (AE) 
o Treatment-emergent AEs 
o Treatment related AEs 
o SAEs and AEs leading to discontinuation 
• Clinically significant abnormalities in vital signs 
• Clinically significant abnormalities in clinical laboratory values. 
3.5.1. Adverse Events 
Any events occurring following start of treatment will be considered as treatment emergent 
adverse event (TEAE). Events that occur in a non-treatment period (ie follow-up period) 
within the lag time of 28 days will be counted as treatment emergent and attributed to the 
previous treatment taken. Similarly, the time period for collecting AEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent. 
3.5.2. Vital Signs 
Blood Pressure (BP) and Pulse Rate (PR) will be measured at times specified in the SoA 
given in the protocol. The baseline measurement is the latest measurement during the 
Screening period. 
3.5.3. Laboratory Data 
Safety laboratory tests will be performed as described in the protocol. To determine if there 
are any clinically significant laboratory abnormalities, the haematological, clinical chemistry 
(serum) and urinalysis safety tests will be assessed against the criteria specified in the 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 8 of 13 
 
 
sponsor reporting standards. The assessment will not take into account whether each 
participants’ baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter. 
For each laboratory parameter, the baseline measurement is the latest measurement during 
the Screening period. 
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 releasing the database and classifications will 
be documented per standard operating procedures. 
For purposes of analysis, the following analysis sets are defined: 
 
Population 
Description 
PK Concentration 
The PK concentration population is defined as all participants 
treated who have at least 1 concentration. 
PK Parameter 
The PK parameter analysis population is defined as all 
participants treated who have at least 1 of the PK parameters 
of primary interest. 
PD Parameter 
The PD parameter analysis population is defined as all 
participants treated who have at least 1 of the PD parameters 
of primary interest. 
Safety 
All participants assigned to study intervention and who take at 
least 1 dose of study intervention. Participants will be 
analyzed according to the product they actually received. 
5. GENERAL METHODOLOGY AND CONVENTIONS 
Final analysis will be performed after study participant data set release following last 
participant last visit. 
5.1. Hypotheses and Decision Rules 
No statistical hypothesis will be tested in this study. 
5.2. General Methods 
5.2.1. Analyses for Binary Endpoints 
For binary or categorical variables, number of participants, numbers and percentages of 
participants meeting the categorical criteria will be presented in accordance with the Clinical 
Data Interchange Standards Consortium and Pfizer Standards (CaPS). 
5.2.2. Analyses for Continuous Endpoints 
For continuous variables, the data will be summarized using the number of participants, 
mean, standard deviation (SD), Interquartile Range (IQR), minimum, and maximum in 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 9 of 13 
 
 
accordance with the CaPS. For appropriate PK parameters, geometric mean and geometric 
coefficient of variation (%CV) will also be summarized. 
5.3. Methods to Manage Missing Data 
5.3.1. Pharmacokinetic Data 
Methods to handle missing PK data are described below. 
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.). 
Deviations, Missing Concentrations and Anomalous Values: 
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true: 
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample). 
2. 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. 
An anomalous concentration value is one that, after verification of bioanalytical validity, is 
grossly inconsistent with other concentration data from the same individual or from other 
participants. For example, a BLQ concentration that is between quantifiable values from the 
same dose is considered as anomalous. Anomalous concentration values may be excluded 
from PK analysis at the discretion of the PK analyst. 
PK 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 not be presented for a particular treatment group if more 
than 50% of the data are NC. For statistical analyses, PK parameters coded as NC will also 
be set to missing. 
If an individual participant has a known biased estimate of a PK parameter (due for example 
to dosing error), this will be footnoted in summary tables and will not be included in the 
calculation of summary statistics or statistical analyses. 


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5.3.2. Pharmacodynamic Data 
Missing data for PD endpoints will be treated as such and no imputed values will be derived 
when presenting descriptive statistics at scheduled assessments. 
5.3.3. Safety Data 
Missing values in standard summaries of AEs, laboratory data, and vital signs will be 
imputed according to CaPS. 
6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoint(s) 
The primary endpoint is the AUC24 on Day 7. The parameter will be summarized 
descriptively, as applicable, in accordance with Pfizer data standards. 
The analysis population will be used for the primary endpoint analysis are the PK 
Concentration set and PK parameter sets. 
6.2. Secondary Endpoint(s) 
6.2.1. PK endpoints 
The plasma PK parameters will be summarized descriptively, as applicable, in accordance 
with Pfizer data standards. Individual participant and median profiles of the plasma 
concentration-time data will be plotted using actual and nominal times, respectively. Median 
profiles will be presented on both linear-linear and log-linear scales. Plasma concentrations 
will be listed and summarized descriptively by nominal PK sampling time. 
Each PK parameter will be summarized and will include the set of summary statistics as 
specified in Table 3. 
 
Table 3. 
PK Parameters to be Summarized Descriptively by Treatment 
 
Parameter 
Summary Statistics 
AUC24, Cmax, 
CL/F, Vz/F 
N, arithmetic mean, median, SD, %CV, minimum, maximum, geometric 
mean and geometric %CV 
Tmax 
N, median, minimum, maximum 
t½ 
N, arithmetic mean, median, SD, %CV, minimum, 
Maximum 
6.2.2. PD Endpoints 
All of the PD endpoints will be summarized by time point and change from baseline for these 
endpoints will also be summarized at specific time points as reported in the SoA. 


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Page 11 of 13 
 
 
6.2.3. Taste Assessment Analyses 
Taste acceptability data will be listed and summarized descriptively (frequencies and 
percentages) at day 7 among all participants assigned to study intervention and who take at 
least 1 dose of study intervention. 
6.2.4. Safety data 
See Section 6.5. 
6.3. Subset Analyses 
There are no planned subset analyses. 
6.4. Baseline and Other Summaries and Analyses 
6.4.1. Baseline Summaries 
Demographic characteristics (age, gender, ethnicity, race, weight, height and body mass 
index) will be summarized for enrolled population in accordance with the CaPS. The safety 
analysis set will be considered for the analysis. 
6.4.2. Study Conduct and Participant Disposition 
Participants evaluation groups will show end of study participant disposition. Frequency 
counts will be supplied for participant discontinuation(s) by treatment. Data will be reported 
in accordance with the CaPS. 
6.4.3. Study Treatment Exposure 
Study treatment exposure will be listed. 
6.4.4. Concomitant Medications and Nondrug Treatments 
All concomitant medication(s) as well as non-drug treatment(s) will be reported in the 
listings. 
6.5. Safety Summaries and Analyses 
All safety analyses will be performed on the Safety Analysis Set. 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate. 
6.5.1. Adverse Events 
Adverse events will be reported in accordance with the CaPS. 
Participant discontinuations due to adverse events will be detailed. Data will be reported in 
accordance with the CaPS. 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
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Page 12 of 13 
 
 
6.5.2. Laboratory Data 
Laboratory data will be listed and summarized in accordance with the CaPS. 
6.5.3. Vital Signs 
Vital sign data will be databased and available upon request. 
7. INTERIM ANALYSES 
No formal interim analysis will be conducted for this study. As this is an open-label study, the 
sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK modeling, and/or supporting clinical 
development. 
Final analysis will follow the official database release. As this will be an open-label study, 
there is no formal unblinding of the randomization code. 


Protocol B7981031 (PF-06651600) Statistical Analysis Plan 
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Page 13 of 13 
 
 
APPENDICES 
Appendix 1. List of Abbreviations 
 
Abbreviation 
Term 
AA 
alopecia areata 
ADL 
activity/activities of daily living 
AE 
adverse event 
AESI 
adverse event of special interest 
AUC 
Area under the concentration-time curve 
AUC24 
Area under the plasma concentration time profile over the dosing 
interval 24 hrs, at steady-state 
BLQ 
below the limit of quantitation 
BP 
blood pressure 
CaPS 
CDISC and Pfizer Standards 
CDISC 
Clinical Data Interchange Standards Consortium 
C-SSRS 
Columbia – Suicide Severity Rating Scale 
CL 
apparent clearance 
CL/F 
apparent clearance after oral dose 
Cmax 
maximum plasma concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
eSAE 
electronic serious adverse event 
HR 
heart rate 
IQR 
Interquartile Range 
NK 
natural killer 
OIRC 
Opportunistic Infection Review Committee 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
QD 
once daily 
SAE 
serious adverse event 
SALT 
Severity of Alopecia Tool 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SoA 
schedule of activities 
TEAE 
Treatment emergent adverse event 
Tmax 
time to reach Cmax 
t½ 
terminal elimination half-life 
VZ/F 
Apparent volume of distribution after oral dose 
WOCBP 
woman/women of childbearing potential