A Study to Learn About the Study Medicine Called PF-08049820 in People With Eczema, an Itchy Skin Rash

Prior treatment

• Undergone significant trauma or surgery within 1 month prior to screening.
• Use of any prohibited concomitant medication(s). Refer to Section 6.9 and Appendix 9.
• Treatment with a live (attenuated) vaccine within 12 weeks of Day 1 visit or planned during the study.
• Inadequate response to anti-inflammatory protein therapeutics and/or systemic JAK inhibitors.
• Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, "CCI", antiprotozoals, or antifungals within 2 weeks before Day 1 visit or superficial skin infections within 1 week before Day 1 visit. Note: participants may be rescreened after infection resolves.
• A history (within approximately 3 months prior to Day 1) of systemic, chronic or acute skin infection requiring hospitalization, parenteral antimicrobial therapy (within approximately 2 weeks prior to Day 1), or as otherwise judged clinically significant by the investigator.
• Current or recent history (within approximately 3 months prior to Day 1) of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
• Currently on any suppressive therapy for a chronic infection (such as pneumocystis, CMV, and atypical mycobacteria) that, in the opinion of the investigator and sponsor, would place the participant at risk for reactivation. Participants receiving prophylactic therapy for prior outbreaks of herpes simplex virus or herpes zoster may be enrolled with the expectation that this treatment will continue for the duration of the study.

Other illness

• Have current or a history of alcohol abuse or binge drinking and/or any other illicit drug use or dependence in the past 2 years which, in the opinion of the investigator, could create a risk for the participant’s health or protocol adherence. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
• Hypersensitivity to PF-08049820 or to the excipients of the formulated drug products. Participants with significant reactions to single, identified, avoidable allergens (eg, peanut allergy) may be eligible if avoidance of these allergens during the study is feasible. Participants with such a history need to have and know how to use an epinephrine injection (eg, EpiPen).
• Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, comorbid severe uncontrolled asthma or a history ≥2 asthma exacerbations within the last 12 months requiring systemic (oral and/or parenteral) corticosteroid treatment or hospitalization for >24 hours. a. Participants with well controlled mild to moderate asthma according to recognized standard of care treatment guidelines (eg, GINA 2025 Step 1-4 treatment) and having FEV1 > 70% predicted are eligible.
• A history of cancer within 5 years or has undergone treatment for any type of cancer at the time of screening, with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ with no evidence of recurrence.
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, Hepatitis B or C. Refer to Section 8.3.5, Section 8.3.6, and Appendix 2.
• Evidence of active or latent TB, or history of inadequately treated infection with Mycobacterium TB. See Section 8.3.7 and Appendix 2.

Lab values

• Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. a. At screening visit, if there are “yes” answers on items 4 or 5 in the past year or on any question in the suicidal behavior section of the C-SSRS in the past 5 years, the participant will not be included in the study. b. At screening visit, if the PHQ-8 total score is ≥15 at screening the participant will be excluded from the study. c. At Day 1 visit, if there are “yes” answers on items 4, 5 of the suicidal ideation subscale or on any behavioral question of the Since Last Visit C‑SSRS, the participant will not be dosed and will be discontinued from the study.
• Renal impairment as defined by eGFR <60 mL/min/1.73 m², which may be confirmed by a single repeat test, if necessary.
• Hepatic dysfunction defined as having any 1 of the following, which may be confirmed by a single repeat test, if necessary:  Total bilirubin ≥1.5 × ULN (For Gilbert’s syndrome, direct bilirubin > ULN is exclusionary  AST ≥2.0 × ULN  ALT ≥2.0 × ULN
• Hematologic abnormalities defined as any 1 of the following, which may be confirmed by a single repeat test, if necessary:  ANC ≤1,500/mm3  Platelets ≤120,000/mm3  Hemoglobin: ≤13 g/dL for males; ≤12 g/dL for females

Age

• Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (including, but not limited to, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST segment and/or T wave changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant’s eligibility. Computer-interpreted ECGs should be overread by an investigator experienced in reading ECGs before excluding a participant.

Other

• Presence of skin comorbidities that would interfere with study assessment or response to treatment.
• Regular use (more than 2 visits per week) of a tanning booth/parlor or phototherapy for AD within 4 weeks of the screening visit.
• 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.

• Participants between the ages of ≥18 (or the minimum age of consent in accordance with local regulations) and <65 years old at screening.  Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.  Individuals on HRT and whose menopausal status is in doubt will be required to use 1 of the highly effective non-estrogen hormonal contraception methods if they wish to continue their HRT during the trial (Refer to Section 10.4.4 for the list of acceptable non-estrogen hormonal contraceptive methods for this study). Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before trial enrollment (Section 10.4.3).
• Must meet the following AD criteria: a. Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 6 months prior to Day 1 and have diagnosis of AD confirmed by photographs (at screening) and medical record (if available) (according to Hanifin and Rajka criteria of AD). b. Either an inadequate response to high to very high potency corticosteroids and/or topical calcineurin inhibitor for at least 4 consecutive weeks within 1 year of the first dose of the study intervention to ensure that treatment with systemic immunosuppressant therapy is appropriate; OR A documented reason why the above treatments are considered medically inappropriate (eg, because of important side effects, safety risks, documented patient aversion to topical treatment [eg, “grease”], documented patient negation to topical treatment due to other reasons [eg, time or cosmetic appearance], or physical inability to apply topical medications [eg, joint immobility]) within the last year. c. Naïve to anti-inflammatory protein therapeutics and/or systemic JAK inhibitors or have responded to prior anti-inflammatory protein therapeutics and/or systemic JAK inhibitors but lost access (e.g. insurance changes) or had intolerance/AEs. Participants who have had inadequate response to anti-inflammatory protein therapeutics and/or systemic JAK inhibitors are ineligible. d. Moderate to severe AD at both the screening and baseline visits as defined by the following: i. BSA ≥10% and up to 60% (15% cap will be placed on the number of participants with BSA ≥41% to 60%); ii. vIGA ≥3; iii. EASI ≥16; AND iv. PP-NRS ≥4 at screening and weekly average PP-NRS of ≥4 at baseline from 7 days to 1 day prior to randomization. Four or more daily PPNRS entries are needed to calculate the weekly average.
• BMI of 18 to 38 kg/m2 and a total body weight >48 kg (106 lbs).
• Willing and able to comply with all scheduled visits, treatment plan and study procedures.
• Capable of understanding and giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.