Efficacy and Safety Evaluation of PF-07275315 and PF-07264660 in Adults with Moderate to Severe Atopic Dermatitis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to compare the **efficacy** of PF-07275315 and PF-07264660 versus placebo using measures of the Eczema Area and Severity Index (EASI) in participants with moderate to severe **atopic dermatitis**. This is clinically relevant as it aims to determine the potential of these investigational drugs to improve the condition of patients suffering from this chronic inflammatory skin disease, which can significantly impact quality of life.

Secondary objectives include:

• Comparing the efficacy of PF-07275315 and PF-07264660 versus placebo using measures of the Validated Investigator Global Assessment (vIGA) in participants with moderate to severe atopic dermatitis.
• Characterizing the safety and tolerability of PF-07275315 and PF-07264660 versus placebo in participants with moderate to severe atopic dermatitis.

The clinical trial involves a total of **285 participants** diagnosed with **moderate to severe atopic dermatitis**. The study population includes both male and female subjects aged 18 years or older. Participants were selected based on their clinical diagnosis of chronic atopic dermatitis for approximately six months prior to the study's commencement, with confirmation of the diagnosis using the Hanifin and Rajka criteria. The trial excludes vulnerable populations and focuses on individuals who have either shown an inadequate response to standard care treatments, excluding systemic immunosuppressants, or have a documented reason for the inappropriateness of such treatments. The participants' general health status is characterized by moderate to severe atopic dermatitis, defined by an affected body surface area of 10% or more, a validated Investigator Global Assessment score of 3 or higher, and an Eczema Area and Severity Index score of 16 or higher. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of PF-07275315 and PF-07264660 in adult participants with moderate-severe **atopic dermatitis**. The primary objective is to compare the efficacy of these investigational products versus placebo using the Eczema Area and Severity Index (EASI) in participants. The trial is expected to commence recruitment on July 31, 2024, and conclude by February 13, 2026. Participants will be involved in the study for a duration that includes multiple visits, starting with an inclusion (screening) visit, followed by scheduled follow-up visits, and concluding with an end-of-study visit.

The inclusion visit will assess eligibility based on criteria such as age (18 years or older) and a clinical diagnosis of chronic atopic dermatitis for approximately six months prior to Day 1. Participants must have a moderate to severe condition, defined by an affected body surface area of at least 10%, a validated Investigator Global Assessment (vIGA) score of 3 or more, and an EASI score of 16 or higher. Follow-up visits will occur at predetermined intervals to monitor the primary endpoint, which is achieving EASI75 (≥75% improvement from baseline) at Week 16, and secondary endpoints, including vIGA score improvements and incidence of treatment-emergent adverse events.

The expected length of participant involvement is determined by the trial's schedule, with early termination possible if participants experience significant adverse events or fail to adhere to the study protocol. The study is not categorized as low intervention, and the investigational products are biologics developed by Pfizer Inc. The trial will ensure rigorous monitoring of safety and efficacy through regular assessments of vital signs, electrocardiograms, and laboratory tests. Participants will be randomly assigned to receive either the investigational products or placebo, maintaining the double-blind nature of the study to ensure unbiased results.

The clinical trial involves the investigation of two **experimental medications**: PF-07275315 and PF-07264660, both developed by Pfizer Inc. PF-07275315 is identified by the sponsor product code PF-07275315 and is classified as a biologic. The active substance is of protein origin, specifically categorized as "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration are not specified in the available data. Participant compliance will be monitored throughout the study to ensure adherence to the dosing schedule.

Similarly, PF-07264660, also developed by Pfizer Inc., is identified by the sponsor product code PF-07264660 and is classified as a biologic. Like PF-07275315, its active substance is of protein origin, categorized as "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration are not detailed in the provided information. Monitoring of participant compliance will be conducted to maintain adherence to the prescribed dosing regimen.

The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy and safety of the experimental medications. The placebo is administered in a manner consistent with the experimental treatments, although specific details regarding its pharmaceutical form, dosage, route, and frequency of administration are not provided. The use of a placebo is integral to maintaining the double-blind nature of the study, ensuring unbiased assessment of the treatment effects.

The efficacy of PF-07275315 and PF-07264660 in the treatment of moderate to severe **Atopic Dermatitis** will be assessed using the Eczema Area and Severity Index (EASI). The primary endpoint is the achievement of EASI75, defined as a ≥75% improvement from baseline, at Week 16. Secondary endpoints include the Investigator's Global Assessment (vIGA) score of clear (0) or almost clear (1) with a reduction from baseline of ≥2 points at all scheduled time points, EASI75 at scheduled time points other than Week 16, and the percent change from baseline in the EASI total score at scheduled time points. Additionally, the incidence of treatment-emergent adverse events (AEs), and clinically significant changes in vital signs, electrocardiogram (ECG), and laboratory tests will be monitored.