Phase 3 Study on the Safety and Efficacy of Upadacitinib Versus Dupilumab in Pediatric Patients Aged 2-12 with Moderate to Severe Atopic Dermatitis

The primary objective of this study is to evaluate the **efficacy** and safety of **upadacitinib** compared to **dupilumab** in pediatric subjects aged 2 to less than 12 years with moderate to severe atopic dermatitis who are candidates for systemic therapy. Clinically, this is significant as it aims to determine the most effective treatment option for this age group, potentially improving management strategies for atopic dermatitis. The primary efficacy objective outside the US is to assess the proportion of subjects achieving EASI 75 response at Week 16 with upadacitinib 15 mg daily adult equivalent dose compared to dupilumab. For the US and China, the primary efficacy objective is to evaluate the proportion of subjects achieving vIGA-AD 0 or 1 with a reduction from Baseline of ≥ 2 points at Week 16 for each treatment arm, with dupilumab serving as a reference for upadacitinib 15 mg daily adult equivalent dose.

The secondary efficacy objective is to assess the proportion of subjects achieving the dichotomous secondary endpoints and the mean of continuous endpoints based on the ITT population for each treatment arm. Dupilumab will serve as a reference arm for both upadacitinib 15 mg and 7.5 mg daily adult equivalent doses, and the higher dose of upadacitinib will be a reference arm for the lower dose. This evaluation is crucial for understanding the comparative effectiveness of different dosing regimens of upadacitinib relative to dupilumab, thereby informing optimal dosing strategies.

The clinical trial involves a total of **475 participants** diagnosed with **atopic dermatitis**. The study population consists of pediatric subjects aged 2 to less than 12 years, with both male and female participants included. The trial specifically targets individuals with moderate to severe atopic dermatitis who are candidates for systemic therapy. Participants were selected based on specific inclusion criteria, including a minimum weight of 10 kg and a weight and height above the 5th percentile for their age. The trial population includes individuals with a history of inadequate response or intolerance to topical corticosteroids and/or calcineurin inhibitors, or for whom these treatments are medically inadvisable. Additionally, subjects with periocular atopic dermatitis involvement are required to undergo a preliminary ophthalmology assessment. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study aims to assess the efficacy and safety of upadacitinib compared to dupilumab in this vulnerable pediatric population.

The clinical trial is designed to evaluate the **efficacy** and safety of **upadacitinib** compared to **dupilumab** in pediatric subjects aged 2 to less than 12 years with moderate to severe atopic dermatitis. This is a Phase III, open-label, efficacy-assessor-blinded study. The trial employs a randomized, controlled design to ensure robust and unbiased results. The estimated duration of the trial is from November 2024 to May 2030, with a maximum treatment period of 165 days for upadacitinib and 57 days for dupilumab.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, weight, and disease severity. Following the screening, eligible participants will be randomized to receive either upadacitinib or dupilumab. The primary endpoint is the proportion of subjects achieving a 75% reduction in the Eczema Area and Severity Index (EASI 75) at Week 16. Secondary endpoints include various measures of disease improvement and quality of life assessments at different time points.

Study visits will include baseline assessments, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to evaluate overall outcomes. The expected length of participant involvement is up to 165 days, depending on the treatment arm. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or non-compliance with study procedures. The trial aims to provide comprehensive data on the comparative effectiveness of these treatments in managing atopic dermatitis in the specified pediatric population.

The clinical trial involves the administration of **Upadacitinib**, a medication of chemical origin, in two pharmaceutical forms: **modified-release tablet** and **oral solution**. The modified-release tablet form is identified by the sponsor product code ABT-494 and is administered orally. The dosage is expressed in milligrams, although specific dosing information is not provided. The maximum treatment period for this form is 165 days. The oral solution form of Upadacitinib is also administered orally, with the dosage expressed in milligrams per milliliter. This form shares the same maximum treatment period of 165 days. Both forms are not pediatric formulations and are produced by AbbVie Deutschland GmbH & Co. KG.

In addition to Upadacitinib, the trial includes the administration of **Dupilumab**, which serves as a comparator treatment. Dupilumab is a protein-based medication, specifically categorized as a solution for injection. It is administered via subcutaneous injection, with the dosage expressed in milligrams per milliliter. The maximum treatment period for Dupilumab is 57 days. This medication is not a pediatric formulation and is also of chemical origin. Dupilumab is used to assess its efficacy and safety in comparison to Upadacitinib in pediatric subjects with moderate to severe atopic dermatitis.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint for regions other than the US is the percentage of participants achieving a 75% reduction in the Eczema Area and Severity Index Score (**EASI 75**) at Week 16. For the US and China, the primary endpoint is the achievement of a validated Investigator Global Assessment scale for Atopic Dermatitis (**vIGA-AD**) score of 0 or 1, with a reduction from Baseline of ≥ 2 points at Week 16. These assessments will be conducted in the intention-to-treat (ITT) population for each treatment arm.

Secondary endpoints include the percentage of participants achieving a **vIGA-AD** score of 0 or 1 with a reduction from Baseline of ≥ 2 points at various timepoints, such as Week 16, Week 52, and Week 160. Additional secondary measures include the percentage of participants achieving a 50% reduction from Baseline in **EASI** score (EASI 50) at Week 16, improvement in Patient Oriented Eczema Measure (POEM) scores, and changes in the Children's Dermatology Life Quality Index (CDLQI) for participants aged 4 years and older. The trial will also evaluate the percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline at Week 16, the use of topical or systemic rescue therapy, and the number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16.

The efficacy assessments will be conducted at specified timepoints, including Week 16, Week 52, and Week 160, using validated scales and patient-reported outcomes. The trial is designed to compare the efficacy of **Upadacitinib** to **Dupilumab** in pediatric subjects aged 2 to less than 12 years with moderate to severe atopic dermatitis, with **Dupilumab** serving as a reference arm for the **Upadacitinib** 15 mg daily adult equivalent dose.