PF-06700841 Protocol B7931022 Final Protocol, 31 October 2018 Protocol Amendment Summary of Changes Table Document History Document Version Date Summary of Changes and Rationale Original protocol 31 October 2018 Not applicable (N/A) Page 2 PF-06700841 Protocol B7931022 Final Protocol, 31 October 2018 5.3.4.1. Participant Specific Recommendations.....................................45 5.3.4.2. Guidance Regarding Household Contact Vaccine-Related Exposure............................................................................................46 5.3.5. Other Requirements....................................................................................46 5.4. Screen Failures ........................................................................................................47 6. STUDY INTERVENTION..................................................................................................47 6.1. Study Intervention Administered ............................................................................48 6.1.1. Administration ............................................................................................48 6.1.1.1. Treated Atopic Dermatitis Areas...............................................48 6.1.1.2. General Instructions ..................................................................48 6.2. Preparation/Handling/Storage/Accountability ........................................................50 6.2.1. Preparation and Dispensing ........................................................................51 6.2.2. Investigational Product Accountability ......................................................52 6.2.3. Destruction of Investigational Product Supplies ........................................52 6.3. Measures to Minimize Bias: Randomization and Blinding.....................................52 6.3.1. Allocation to Investigational Product .........................................................52 6.3.2. Breaking the Blind......................................................................................53 6.4. Study Intervention Compliance...............................................................................53 6.5. Concomitant Therapy..............................................................................................54 6.5.1. Rescue Medicine.........................................................................................55 6.6. Dose Modification...................................................................................................55 6.7. Intervention after the End of the Study ...................................................................55 7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL...........................................................................55 7.1. Discontinuation of Study Intervention ....................................................................55 7.1.1. ECG Changes..............................................................................................56 7.1.2. Local Tolerability .......................................................................................56 7.1.3. Adverse Events ...........................................................................................56 7.1.3.1. Serious Infections......................................................................57 7.1.3.2. Treated Infections......................................................................57 7.1.4. Potential Cases of Decreased eGFR ...........................................................57 7.1.5. Laboratory Abnormalities...........................................................................58 7.1.6. Pregnancy ...................................................................................................58 Page 4 PF-06700841 Protocol B7931022 Final Protocol, 31 October 2018 7.1.7. Suicidal Ideation and Behavior...................................................................58 7.1.8. Temporary Discontinuation........................................................................59 7.1.9. Discontinuation/End of Treatment Monitoring for Adverse Events, Laboratory, and Vital Signs .............................................................................59 7.2. Participant Discontinuation/Withdrawal from the Study........................................59 7.3. Lost to Follow-up ....................................................................................................60 8. STUDY ASSESSMENTS AND PROCEDURES...............................................................61 8.1. Efficacy Assessments..............................................................................................62 8.1.1. Rater Qualifications....................................................................................62 8.1.2. Investigator’s Global Assessment (IGA)....................................................62 8.1.3. Eczema Area and Severity Index (EASI) ...................................................63 8.1.3.1. Lesion Severity by Clinical Signs .............................................63 8.1.3.2. Percent BSA with Atopic Dermatitis (for efficacy) ..................64 8.1.3.3. Calculation of EASI Score ........................................................65 8.1.4. Body Surface Area......................................................................................66 8.1.4.1. Body Surface Area for IP need .................................................66 8.1.5. Peak Pruritus Numerical Rating Scale (PP-NRS) ......................................67 8.2. Safety Assessments .................................................................................................67 8.2.1. Assessments at Screening Only..................................................................67 8.2.1.1. Medical History.........................................................................67 8.2.1.2. Tuberculosis Testing .................................................................68 8.2.1.3. Chest Radiograph ......................................................................69 8.2.1.4. Skin Type Assessment ..............................................................69 8.2.2. Assessments during Study ..........................................................................69 8.2.2.1. Physical Examinations ..............................................................69 8.2.2.2. Vital Signs .................................................................................70 8.2.2.3. Electrocardiograms....................................................................71 8.2.2.4. Herpetiform Rash ......................................................................72 8.2.2.5. Clinical Safety Laboratory Assessments...................................72 8.2.2.6. Creatinine, Cystatin C, and estimates of Glomerular Filtration Rate....................................................................................73 8.2.2.7. Samples for Lipid Analysis .......................................................73 8.2.2.8. Suicidal Ideation and Behavior Risk Monitoring......................74 Page 5 PF-06700841 Protocol B7931022 Final Protocol, 31 October 2018 1. PROTOCOL SUMMARY 1.1. Synopsis Short Title: A Phase 2b, multicenter, randomized, double-blind, vehicle controlled, parallel group dose ranging study to assess efficacy, safety, tolerability, and pharmacokinetics (PK) of PF-06700841 cream in participants with mild or moderate atopic dermatitis. Rationale: This multicenter, randomized, double-blind, vehicle controlled, parallel group, dose ranging study is being conducted to provide data on efficacy, safety, tolerability and PK of multiple topical formulation concentrations of PF-06700841 topical cream in the treatment of mild-to-moderate atopic dermatitis (AD). This is the first study where a PF-06700841 cream formulation is being applied topically to participants with AD. Additionally, the study is intended to enable selection of the dose and dosing regimen (once daily [QD] vs twice daily [BID] application) for the future clinical development of topical PF-06700841. Objectives, Endpoints and Estimands:a Objectives Endpoints Estimandsb Primary Objective Primary Endpoint(s) Primary Estimands To compare the efficacy of Percent change from baseline in EASI Estimand E1: This estimand is multiple dose levels of total score at Week 6. intended to provide a PF-06700841 topical cream population level estimate of versus vehicle applied QD or the treatment effect of the BID, on percent change from investigational product (IP) on baseline in Eczema Area and a continuous endpoint; without Severity Index (EASI) in the benefit of additional participants with mild or prohibited medications during moderate atopic dermatitis (AD). treatment and regardless of participant compliance with the IP dosing. Secondary Objective(s): Secondary Endpoints Secondary Estimands To compare the efficacy of Key Secondary Endpoint: Estimand E2: This estimand is