Efficacy and Safety Evaluation of Eblasakimab in Moderate-to-Severe Atopic Dermatitis Patients Previously Treated with Dupilumab: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of eblasakimab in participants with moderate-to-severe **Atopic Dermatitis** (AD) who have been previously treated with dupilumab. This is clinically relevant as it aims to determine the potential of eblasakimab as an effective treatment option for patients who may not have achieved desired outcomes with dupilumab, thereby addressing an unmet need in this patient population.

Secondary objectives include:

• To evaluate the **safety** and **tolerability** of eblasakimab in the same patient cohort. This is crucial for understanding the risk-benefit profile of eblasakimab and ensuring that it is a viable therapeutic option for long-term management of moderate-to-severe AD.

The clinical trial involves a total of **25 participants** diagnosed with **Atopic Dermatitis** (AD). The study population includes both male and female subjects aged 18 years and older, who have been previously treated with dupilumab. Participants are required to have moderate-to-severe chronic AD, with a history of the condition for at least one year prior to the screening visit. The trial population was selected based on specific criteria, including a vIGA score of 3 or higher and at least 10% body surface area involvement of AD at baseline. Additionally, participants must have an EASI score of 18 or higher at both the screening and baseline visits. The study includes individuals who have had an inadequate response, intolerance, or contraindication to topical corticosteroids or calcineurin inhibitors. Lifestyle considerations such as diet and physical activity are not specified. The trial does not exclude vulnerable populations, indicating inclusivity in the selection process.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **eblasakimab** in patients with moderate-to-severe **atopic dermatitis** who have previously been treated with dupilumab. The trial will be conducted over a period of 16 weeks, with participants receiving either eblasakimab or a placebo, which is identical in appearance but lacks the active ingredient. The primary endpoint is the percentage change in the Eczema Area and Severity Index (EASI) score from baseline to week 16. Secondary endpoints include various measures of clinical response and quality of life assessments.

Participants will be involved in the study for the entire 16-week duration, with several key visits scheduled throughout the trial. The initial visit will be a screening visit to confirm eligibility based on criteria such as age, chronicity of atopic dermatitis, and previous treatment history with dupilumab. Baseline assessments will be conducted to establish initial disease severity and other relevant health metrics. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment, assess any adverse events, and ensure compliance with the study protocol. The end-of-study visit will involve a comprehensive evaluation of the treatment's efficacy and safety, as well as the collection of final data for analysis.

Participants may be withdrawn from the study prior to completion if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is expected to start recruitment in May 2024 and conclude by February 2025. The study is categorized as a Phase 2 trial, and it is not considered a low-intervention study. The trial's design and procedures are structured to ensure rigorous assessment of eblasakimab's therapeutic potential in the target patient population.

The clinical trial involves the administration of **eblasakimab**, an investigational medication developed by ASLAN Pharmaceuticals. Eblasakimab is provided as a **sterile solution** for **subcutaneous use**. The dosing regimen for eblasakimab includes a maximum daily dose of 600 mg, with a total maximum dose of 6600 mg over a treatment period of 16 weeks. The active substance, eblasakimab, is a protein-based therapeutic agent. The administration schedule and participant compliance are monitored to ensure adherence to the dosing protocol.

The study also includes a **placebo** group, where participants receive a solution identical in appearance to the eblasakimab formulation but without the active ingredient. The placebo consists solely of the excipients used in the eblasakimab formulation, ensuring that it matches the investigational product in terms of pharmaceutical form and route of administration, which is a solution for subcutaneous injection. The use of a placebo allows for a double-blind, controlled comparison to evaluate the efficacy and safety of eblasakimab in patients with moderate-to-severe atopic dermatitis who have previously been treated with dupilumab.

The efficacy of **eblasakimab** in the treatment of moderate-to-severe atopic dermatitis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percentage change in the Eczema Area and Severity Index (EASI) score from Baseline to Week 16. Secondary endpoints include the proportion of participants achieving a validated Investigator Global Assessment (vIGA) response of 0 (clear) or 1 (almost clear) on a 5-point scale at Week 16, and the proportion of participants with a 75% reduction from Baseline in EASI (EASI 75) at Week 16. Additional secondary endpoints involve the proportion of participants achieving EASI 50 and EASI 90, the proportion of participants with EASI <7, and changes in various patient-reported outcomes and clinical measures from Baseline to Week 16.

These secondary measures include absolute and percent change in peak Pruritus Numerical Rating Scale (P-NRS), the proportion of participants achieving a 4-point reduction in peak P-NRS, change in Body Surface Area (BSA) affected with atopic dermatitis, and changes in SCORing Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and EQ-5D-5L. Additionally, absolute and percent change in Sleep Disturbance Numerical Rating Scale (SD-NRS) and the proportion of participants achieving a 4-point reduction in SD-NRS will be evaluated. The study will also monitor adverse events (AEs) and serious adverse events (SAEs), including clinically significant changes in vital signs, clinical laboratory tests, and electrocardiograms (ECGs).