A 2-year Open-label Extension Study to Assess the Long-term Safety and Efficacy of Lebrikizumab in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis

The primary objective of this study is to examine the long-term **tolerability** of lebrikizumab 250 mg administered every four weeks (Q4W) in adults and adolescents with moderate-to-severe **Atopic Dermatitis**. This will be assessed by monitoring treatment discontinuations due to adverse events over a period of two years. Understanding the tolerability of lebrikizumab is clinically relevant as it informs healthcare providers about the safety profile of the treatment, which is crucial for long-term management of the condition.

Secondary objectives include:

• Evaluating the effectiveness of lebrikizumab 250 mg Q4W in controlling disease signs and symptoms over a two-year period in the same patient population. This is important for determining the sustained efficacy of the treatment in managing the clinical manifestations of Atopic Dermatitis.
• Assessing the impact of lebrikizumab 250 mg Q4W on patient-reported quality of life over the same duration. This objective is significant as it provides insights into the broader effects of the treatment on patients' daily lives and overall well-being.

The clinical trial focuses on evaluating the long-term tolerability of **lebrikizumab** 250 mg Q4W in individuals with moderate-to-severe **Atopic Dermatitis**. The study population includes both male and female participants, encompassing a broad age range from adolescents to adults. The trial involves a vulnerable population, indicating that special considerations are in place to ensure participant safety and compliance with ethical standards. The sponsor has not provided the total number of participants involved in the study. Participants were selected based on their completion of treatment with lebrikizumab in a previous study, ADjoin, and their ability to understand the trial's purpose and risks. Additionally, women of childbearing potential are required to adhere to specific contraceptive guidelines during the study period. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria emphasize the participants' ability to comply with the protocol and provide informed consent, ensuring that all individuals are fully aware of the study's requirements and potential risks.

The clinical trial is designed as a 108-week, open-label extension study to evaluate the long-term safety and efficacy of **lebrikizumab** in adult and adolescent patients with moderate-to-severe **atopic dermatitis**. The trial involves administering lebrikizumab 250 mg every four weeks (Q4W) via subcutaneous injection. The primary objective is to assess the long-term tolerability of the treatment, focusing on discontinuations due to adverse events over the two-year period. Secondary endpoints include various efficacy measures such as the percentage of patients achieving specific reductions in Eczema Area and Severity Index (EASI) scores and improvements in other dermatological assessments.

Participants eligible for this study are those who have completed treatment in a previous study, ADjoin, and have attended their last assessment visit. The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria, which include the ability to understand the trial's purpose and risks, and compliance with contraceptive requirements for women of childbearing potential. Following the screening, participants will undergo regular follow-up visits to monitor safety and efficacy outcomes, with assessments conducted at specified intervals throughout the study duration.

The expected length of participant involvement is approximately 108 weeks, with the study estimated to conclude by March 2026. Conditions that may lead to early termination from the study include the occurrence of treatment-emergent adverse events that necessitate discontinuation. The trial's design does not include a control group, as it is an extension study focusing on long-term outcomes. Participants will be closely monitored to ensure adherence to the protocol and to evaluate the sustained impact of lebrikizumab on atopic dermatitis symptoms.

The clinical trial involves the administration of **Lebrikizumab**, a monoclonal antibody, as the experimental medication. Lebrikizumab is provided in the form of a **solution for injection**. The pharmaceutical preparation is a 250 mg solution for injection, specifically designed for **subcutaneous use**. The solution is delivered in a pre-filled syringe with a needle safety device, constituting a Drug Device Combination Product. Each syringe contains 2 mL of a 125 mg/mL lebrikizumab solution, ensuring a single-dose administration. The maximum daily and total dose is 250 mg, administered once every four weeks (Q4W). The treatment period extends up to 106 weeks, allowing for long-term assessment of safety and efficacy in patients with moderate-to-severe **atopic dermatitis**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on evaluating the long-term tolerability and efficacy of lebrikizumab. Participant compliance is monitored through regular follow-ups and assessments to ensure adherence to the dosing schedule. The trial aims to gather comprehensive data on the safety profile of lebrikizumab, particularly concerning treatment discontinuations due to adverse events over the two-year period.

The efficacy of Lebrikizumab in the clinical trial will be assessed using several key endpoints. The primary endpoint is the proportion of patients who discontinue the study treatment due to treatment-emergent adverse events (AEs) through the last study visit. Secondary endpoints include the percentage of patients achieving specific reductions in the Eczema Area and Severity Index (EASI) scores, specifically EASI 50, EASI 75, and EASI 90, which correspond to ≥50%, ≥75%, and ≥90% reduction from baseline of the parent study, respectively. Additionally, the percentage change from baseline in EASI score by visit, and the percentage of patients with an EASI score ≤7 by visit will be evaluated.

Further secondary endpoints involve the percentage of patients achieving an Investigator's Global Assessment (IGA) score of 0/1, and the percentage achieving a Pruritus Numerical Rating Scale (NRS) score of 0/1 or ≤4 by visit. The trial will also assess the percentage change from baseline in the Patient-Oriented Eczema Measure (POEM) and Body Surface Area (BSA) involvement by visit. The proportion of topical corticosteroid (TCS)-free days from baseline by visit will be recorded, along with the percentage of patients with a Dermatology Life Quality Index (DLQI) score ≥4 at baseline achieving a ≥4-point improvement, and those with a Children's Dermatology Life Quality Index (CDLQI) score ≥6 at baseline achieving a ≥6-point improvement from baseline of the parent study by visit. The percentage of participants achieving DLQI ≤5 and CDLQI ≤6 by visit will also be measured.