The purpose of this study is to learn if the study medicine (PF-08049820) is safe and effective for the treatment of atopic dermatitis (AD), also known as eczema, or atopic eczema. People with this condition may have severe itching and rashes on the skin.

The study is seeking participants who:

1. Are aged 18 years or older;
2. Were confirmed to have AD at least 6 months ago;
3. Do not have a suitable prescribed medicine for AD;
4. Are considered by their doctors to have moderate to severe AD.

The study has two stages (Stage 1 and Stage 2). In both stages, eligible participants will take either PF-08049820 or placebo as tablets by mouth daily for 12 weeks. A placebo does not have any medicine in it but looks just like the medicine being studied. Participants will visit the clinic on Day 1, Weeks 1, 2, 4, 6, 8 and 12. They will have a follow-up visit at Week 16. During this time, the participant's health and skin condition will be checked. They will have blood and urine tests. They will also have to answer questions about their health, skin condition, and how much their skin condition affects their lives. The experiences of participants receiving the study medicine will be compared to those receiving placebo. This will help to understand if PF-08049820 is safe and effective.

Inclusion Criteria:

Participants must meet the following criteria:

1. Are 18 years of age or older

2. Have clinical diagnosis of AD for at least 6 months prior to Day 1 and have diagnosis of AD confirmed by photographs

3. Have moderate to severe AD as defined by the following at screening and baseline visits:

   • Affected body surface area (BSA) greater than or equal to 10% and up to 60%;
   • Validated Investigator's Global Assessment (vIGA) greater than or equal to 3;
   • Eczema Area and Severity Index (EASI) greater than or equal to 16;

   AND

   -Peak Pruritis Numeric Rating Scale (PP-NRS) greater than or equal to 4 at screening and a weekly average of greater than or equal to 4 at baseline visit

4. Do not have a suitable prescribed medicine for AD.

5. Body Mass Index (BMI) of 17.5 to 40 kg/m2 and a total body weight greater than 45 kg (100 lbs)

Exclusion Criteria:

Participants must not meet the following criteria:

1. Have an infection that requires treatment
2. Have other skin conditions other than AD
3. Have severe uncontrolled asthma
4. Regular use (more than 2 visits per week) of a tanning booth or phototherapy for AD within 4 weeks of the screening visit

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.