Evaluation of Lebrikizumab Efficacy and Safety in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Phase 3 Randomized Study

The primary objective of this study is to evaluate the **effectiveness** of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe **Atopic Dermatitis** (AD). This is assessed over two parts: Part 1 involves 24 weeks of treatment, while Part 2 extends to 36 weeks for those who achieve a sustained clinical response. The clinical relevance of this objective lies in addressing the significant burden of moderate-to-severe AD, which can severely impact quality of life and is often resistant to conventional therapies.

Secondary objectives include:

• Part 1: Evaluating the impact of 24 weeks of lebrikizumab treatment on patient-reported and investigator-reported outcome measures in the target population.
• Part 2: Assessing the impact of 36 weeks of lebrikizumab 500 mg every 12 weeks and 250 mg every 4 weeks on similar outcome measures in patients who have achieved a sustained clinical response.

The clinical trial involves a total of **50 participants** diagnosed with **Atopic Dermatitis**. The study population includes both **male and female** subjects, comprising adults and adolescents aged **12 years and older**. Participants are required to weigh at least **40 kg** and are candidates for systemic therapy for moderate-to-severe atopic dermatitis. The trial population was selected based on specific inclusion criteria, including a history of chronic atopic dermatitis for at least one year, an EASI score of 12 or higher, and an IGA score of 3 or more at baseline. Participants must also have at least 10% body surface area involvement and a history of inadequate response to topical treatments. The study considers lifestyle factors such as the ability to complete electronic diary entries for pruritus and sleep-loss. Both genders are included, and the trial does not exclude vulnerable populations. The sponsor has not provided additional information regarding specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **effectiveness** and safety of **lebrikizumab** in adults and adolescents with moderate-to-severe **atopic dermatitis**. This study is structured as a Phase 3, two-part trial, incorporating both open-label and double-blind, randomized methodologies. The trial will span an estimated duration from May 2024 to June 2027. Participants will be randomly assigned to receive either lebrikizumab or a placebo, with the active treatment administered as a subcutaneous injection in pre-filled pens or syringes. The trial consists of two parts: Part 1 involves 24 weeks of treatment, while Part 2 extends the treatment to 36 weeks for those who demonstrate a sustained clinical response.

Study visits are sequenced to ensure comprehensive monitoring and data collection. The initial visit, known as the inclusion or screening visit, will determine participant eligibility based on specific criteria, including age, weight, and disease severity. Participants must have a history of chronic atopic dermatitis and meet certain clinical scores. Follow-up visits will occur regularly throughout the trial to assess treatment efficacy and safety, with primary endpoints evaluated at Week 24 for Part 1 and Week 36 for Part 2. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any post-treatment assessments are completed.

Participant involvement is expected to last up to 60 weeks, depending on their response to treatment and progression to Part 2 of the trial. Conditions that may lead to early termination from the study include adverse reactions, non-compliance with study protocols, or withdrawal of consent. The trial aims to provide robust data on the percentage of participants achieving significant improvements in disease severity and quality of life, as measured by standardized clinical scales and patient-reported outcomes.

The clinical trial involves the administration of **Ebglyss**, a **solution for injection** containing the active substance **lebrikizumab**. This medication is provided in two pharmaceutical forms: a pre-filled pen and a pre-filled syringe, each containing 250 mg of lebrikizumab. The solution is designed for **subcutaneous use** and is administered as a single-dose injection. The pre-filled pen and syringe are part of a Drug Device Combination Product (DDC) that includes a passive safety device to ensure safe administration. The solution is composed of 125 mg/mL lebrikizumab, and the maximum daily dose is 500 mg, with a total maximum dose of 3000 mg over a treatment period of up to 24 weeks. The administration schedule includes a dosage of 500 mg every 12 weeks (Q12W) or 250 mg every 4 weeks (Q4W), depending on the study phase and participant response. Compliance with the dosing schedule is monitored throughout the trial.

A **placebo** is also utilized in this study as a comparator treatment. The placebo is designed to match the appearance and administration route of the active treatment but does not contain any active pharmaceutical ingredient. The use of a placebo allows for the assessment of the treatment's effectiveness by providing a control group for comparison. The placebo is administered following the same schedule as the active treatment to maintain blinding and ensure the integrity of the study results.

The efficacy of **lebrikizumab** in the treatment of moderate-to-severe Atopic Dermatitis (AD) will be assessed through a two-part clinical trial. The primary endpoints for Part 1 include the percentage of participants achieving an Eczema Area and Severity Index (EASI) score of ≤7 at Week 24. In Part 2, the primary endpoints are the percentage of participants achieving EASI 75 at Week 36 and those with an Investigator's Global Assessment (IGA) score of 0 or 1, with a reduction of ≥2 points from baseline at Week 36.

Secondary endpoints for Part 1 include the time to achieve an EASI score of ≤7, the percentage of participants achieving EASI ≤5 and ≤3 at Week 24, and the percentage achieving EASI 75 and EASI 90 at Week 24. Additional secondary endpoints involve the percentage of participants with an IGA score of 0 or 1 and a reduction of ≥2 points at Week 24, as well as improvements in SCORAD, mTLSS, Pruritus NRS, DLQI/cDLQI, Sleep-Loss Scale, and POEM scores. For Part 2, secondary endpoints include similar measures at Week 36, focusing on EASI scores, pruritus, quality of life, sleep loss, and disease control.

Efficacy assessments will be conducted at specified timepoints, including Week 24 for Part 1 and Week 36 for Part 2. The trial will utilize validated scales and patient-reported outcomes to measure these parameters. The study aims to evaluate the effectiveness of lebrikizumab administered as a 250 mg solution for injection in pre-filled syringes or pens, with a maximum treatment period of 24 weeks for each part of the trial.