A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects with Moderate to Severe Atopic Dermatitis

The primary objective of this study is to assess the **efficacy** and **safety** of upadacitinib in adolescent and adult subjects with moderate to severe **Atopic Dermatitis** who are candidates for systemic therapy. This evaluation is clinically relevant as it aims to provide insights into the potential of upadacitinib as a therapeutic option for individuals suffering from this chronic inflammatory skin condition, which can significantly impact quality of life.

Secondary objectives include:

• Assessing the efficacy and safety of 15 mg and 30 mg upadacitinib for the treatment of adolescent and adult subjects with moderate to severe Atopic Dermatitis through up to 260 weeks in subjects who have completed week 16.

The clinical trial involves a total of **725 participants** diagnosed with **moderate and severe atopic dermatitis**. The study population includes both male and female subjects aged between **12 and 75 years**. Participants were selected based on their active moderate to severe atopic dermatitis, as defined by EASI, IGA, BSA, and pruritus, and their candidacy for systemic therapy or recent requirement for such therapy. The trial encompasses a diverse group, including adolescents and adults, with no specific lifestyle considerations such as diet or physical activity mentioned. The selection criteria ensure that the participants are representative of those who would typically require systemic treatment for atopic dermatitis, thereby providing a relevant sample for assessing the efficacy and safety of upadacitinib in this population.

The clinical trial is a **Phase 3**, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of **upadacitinib** in adolescent and adult subjects with moderate to severe **atopic dermatitis**. The trial aims to assess the therapeutic potential of upadacitinib, a Janus kinase (Jak) 1 inhibitor, in individuals who are candidates for systemic therapy. The study will involve male and female participants aged 12 to 75 years, who have active moderate to severe atopic dermatitis as defined by EASI, IGA, BSA, and pruritus, and who are candidates for or have recently required systemic therapy.

The trial is expected to last until October 2025, with an estimated recruitment start date in August 2018. Participants will be randomly assigned to receive either upadacitinib or a placebo, administered orally in the form of modified-release tablets. The maximum treatment period is 260 days, with a daily dose of up to 30 mg for upadacitinib. The primary endpoints include the proportion of subjects achieving a validated IGA scale for atopic dermatitis (vIGA-AD) of 0 or 1 with at least two grades of reduction from baseline at Week 16, and the proportion of subjects achieving an improvement from baseline of at least 75% on the Eczema Area Severity Index (EASI 75) at Week 16.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria. Subsequent visits will include regular follow-up assessments to monitor efficacy and safety, with key evaluations at Weeks 1, 2, 4, and 16. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted. Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study protocols.

The clinical trial involves the administration of **Upadacitinib**, a **Janus kinase (Jak) 1 inhibitor**, in the form of a **modified-release tablet**. The active substance, upadacitinib, is chemically derived and manufactured by AbbVie Deutschland GmbH & Co. KG. The trial includes two dosing regimens: a maximum daily dose of 30 mg and a 15 mg dose, both administered orally. The maximum treatment period is 260 days. The total maximum dose for the 30 mg regimen is 54,600 mg, while for the 15 mg regimen, it is 27,300 mg. The pharmaceutical form is specifically designed for modified release to ensure optimal therapeutic efficacy and patient compliance.

The study also includes a **placebo** group, utilizing a placebo for upadacitinib in the form of a film-coated tablet. The placebo is administered orally, mirroring the administration route of the active treatment to maintain the double-blind nature of the trial. The placebo is used to evaluate the efficacy and safety of upadacitinib by providing a baseline for comparison against the active treatment. The placebo does not contain any active pharmaceutical ingredients and is designed to be indistinguishable from the active treatment in appearance and administration.

The efficacy of **upadacitinib** in the treatment of moderate to severe Atopic Dermatitis will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of subjects achieving a validated Investigator's Global Assessment (vIGA-AD) score of 0 or 1, with at least two grades of reduction from baseline at Week 16, and the proportion of subjects achieving at least a 75% improvement from baseline on the Eczema Area Severity Index (EASI 75) at Week 16.

Secondary endpoints will evaluate additional measures of efficacy, such as the proportion of subjects achieving an improvement in the worst pruritus Numerical Rating Scale (NRS) by at least 4 points from baseline at various time points, including Week 16, Week 4, and Day 2. Other secondary endpoints include the proportion of subjects achieving EASI 90 and EASI 100 at Week 16, as well as changes in the Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Atopic Dermatitis Impact Scale (ADerm-IS) scores. These assessments will be conducted at specified intervals, with key time points at Week 1, Week 2, Week 4, and Week 16.

The efficacy parameters will be measured using validated scales and patient-reported outcomes, ensuring a comprehensive evaluation of the treatment's impact on disease severity, symptom relief, and quality of life. The data collected will be analyzed to determine the overall efficacy of upadacitinib in achieving clinically meaningful improvements in patients with moderate to severe Atopic Dermatitis.