Phase 2b Randomized Double‑Blind Placebo‑Controlled Dose‑Ranging Study of Oral PF‑08049820 in Adults with Moderate‑to‑Severe Atopic Dermatitis

The primary objective is to evaluate the efficacy of multiple oral doses of PF‑08049820 compared with placebo at Week 12 in participants with moderate to severe Atopic Dermatitis, using the Eczema Area and Severity Index (EASI) as the primary endpoint, thereby assessing the drug’s potential to reduce disease severity.

Secondary objectives are to:

• compare the efficacy of PF‑08049820 versus placebo over time using serial EASI measurements;
• compare the efficacy of PF‑08049820 versus placebo over time using the Validated Investigator Global Assessment (vIGA);
• assess the impact of PF‑08049820 versus placebo on itch intensity;
• determine the safety and tolerability profile of PF‑08049820 relative to placebo in this patient population.

The trial enrolled 151 participants who were ≥18 years of age, inclusive of both male and female individuals, and who had a clinical diagnosis of chronic atopic dermatitis for at least six months prior to screening. All participants met the criteria for moderate to severe atopic dermatitis, defined by a body‑surface‑area involvement of ≥10 % and ≤60 % (with a cap on those with ≥41 %), a validated Investigator Global Assessment score of ≥3, an Eczema Area and Severity Index score of ≥16, and a patient‑reported itch numeric rating scale of ≥4 at both screening and baseline. Eligible subjects required a body‑mass index between 17.5 and 40 kg/m² and a total body weight exceeding 45 kg, and they must have demonstrated an inadequate response to topical therapies for at least four consecutive weeks within the preceding year or had a documented contraindication to such treatments. Individuals with prior exposure to anti‑inflammatory protein therapeutics or JAK inhibitors who had an inadequate response were excluded. Enrollment required confirmation of the diagnosis by photographs and medical records, and participants needed to be capable of adhering to scheduled visits, the treatment regimen, and study procedures.

The study is a Phase 2b, randomized, double‑blind, placebo‑controlled, dose‑ranging trial evaluating oral PF‑08049820 tablets versus matching placebo in adult participants with moderate to severe Atopic Dermatitis. Subjects are screened, randomized, and then receive one of several fixed oral doses of the investigational product or placebo in a double‑blind manner. The primary efficacy assessment (percent change in EASI total score) is performed at Week 12, and secondary efficacy and safety evaluations continue through the end‑of‑study visit. The planned participant involvement spans approximately 12 weeks of treatment plus a follow‑up period, with the overall trial recruitment period from May 2026 to July 2027. The visit schedule includes: a screening visit for eligibility confirmation, baseline/randomization visit (Day 1), follow‑up visits at Weeks 2, 4, 8, and 12 for efficacy and safety assessments, and a final end‑of‑study visit at Week 12 (or later if safety follow‑up is required). Early termination may occur if a participant experiences a serious adverse event, violates major protocol criteria (e.g., prohibited medication use, pregnancy), exhibits non‑compliance, or if the investigator determines continuation is not in the participant’s best interest.

The investigational product, PF-08049820, is provided as an oral tablet. The study employs a dose‑ranging design in which participants receive one of several predefined dose levels of the tablet once daily; the specific milligram strength for each cohort is outlined in the randomization schedule. All administrations are performed by mouth, and the tablets are taken with water under fasting conditions unless otherwise specified in the protocol.

The comparator is a matching placebo tablet identical in appearance to the active tablets. The placebo contains no pharmacologically active substance and is administered orally once daily following the same schedule as the investigational product.

Dosing continues for a 12‑week treatment period with visits at regular intervals to assess efficacy and safety. Participant compliance is monitored through returned tablet counts, electronic medication event monitoring system (MEMS) caps, and participant‑completed dosing diaries. Missed doses are recorded, and adherence rates are calculated to ensure protocol compliance.

The primary efficacy assessment will be the percent change from baseline in EASI total score at Week 12. EASI will be evaluated using a validated scoring system applied by trained investigators at baseline and at the 12‑week visit. The change will be calculated relative to each participant’s baseline value.

Secondary efficacy evaluations will include:

• Proportion of participants achieving EASI75 (≥75 % improvement from baseline) at scheduled visits.
• Percent change from baseline in EASI total score at additional scheduled time points.
• Response based on achieving a vIGA score of clear (0) or almost clear (1) with a reduction of ≥2 points from baseline at scheduled visits.
• Response defined as a reduction of ≥4 points in the weekly average of the Peak Pruritus Numerical Rating Scale (PP‑NRS) from baseline at scheduled visits.

Efficacy parameters will be measured using the respective validated instruments (EASI, vIGA 5‑point scale, PP‑NRS). Data will be collected at baseline, Week 12, and any other predefined assessment visits, and will be analyzed according to the study statistical analysis plan.