Evaluation of Dose Flexibility and Efficacy of Upadacitinib in Adults with Moderate to Severe Atopic Dermatitis: A Phase 3b/4 Randomized Study

The primary objective of this study is to evaluate the **efficacy** and **safety** of **upadacitinib** in adult subjects with moderate to severe **atopic dermatitis**. The study is divided into two sub-studies. In Sub-Study 1 (SS1), the focus is on assessing the outcomes of dose escalation to upadacitinib 30 mg once daily (QD) in subjects who do not achieve an Eczema Area and Severity Index (EASI) 90 response on upadacitinib 15 mg QD after 12 weeks. This is clinically relevant as it aims to determine if increasing the dose can improve treatment outcomes for patients not responding adequately to the initial dose. In Sub-Study 2 (SS2), the objective is to evaluate the effects of dose reduction to upadacitinib 15 mg QD in subjects who achieve EASI 90 on upadacitinib 30 mg QD after 12 weeks. This is important for understanding the potential for maintaining efficacy while minimizing drug exposure and potential side effects. No secondary objectives are specified for this study.

The clinical trial involves a total of **166 participants** diagnosed with **atopic dermatitis**. The study population comprises both male and female subjects aged between 18 and 64 years. Participants were selected based on their chronic atopic dermatitis condition, with symptoms having onset at least three years prior to the baseline, and they meet the Hanifin and Rajka criteria. All subjects are candidates for systemic treatment. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **upadacitinib**, a small molecule JAK inhibitor, in adult subjects with moderate to severe atopic dermatitis. This is a Phase 3b/4 randomized, blinded, treat-to-target, and dose-flexibility study. The trial involves two sub-studies: Sub-Study 1 (SS1) focuses on dose escalation to 30 mg once daily (QD) for subjects who do not achieve Eczema Area and Severity Index (EASI) 90 on 15 mg QD after 12 weeks, while Sub-Study 2 (SS2) evaluates dose reduction to 15 mg QD for subjects who achieve EASI 90 on 30 mg QD after 12 weeks. The primary endpoint is the achievement of EASI 90 at Week 24, with secondary endpoints including various measures of improvement in EASI scores, pruritus, and Dermatology Life Quality Index (DLQI) at Weeks 12 and 24.

The trial is expected to last until March 2025, with recruitment starting in May 2023. Participants will be involved for a maximum treatment period of 24 weeks. The study includes an initial screening visit to confirm eligibility, based on criteria such as age (18 to <65 years), chronic atopic dermatitis with symptom onset at least three years prior, and candidacy for systemic treatment. Following the screening, participants will undergo regular follow-up visits to monitor their response to treatment and adjust dosages as necessary. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or withdraw consent. The study is conducted under a double-blind design to ensure unbiased results, with neither participants nor investigators aware of the specific treatment allocations. The trial's methodology is structured to provide robust data on the dose flexibility and long-term safety of upadacitinib in managing moderate to severe atopic dermatitis.

The clinical trial involves the administration of **Upadacitinib**, a small molecule JAK inhibitor, in the form of a **MODIFIED-RELEASE TABLET**. The experimental medication is provided in two dosage strengths: 30 mg and 15 mg. The route of administration is **ORAL**, and the medication is taken once daily (QD). The maximum daily dose for the 30 mg formulation is 30 mg, with a total maximum dose of 5040 mg over a treatment period of 24 weeks. For the 15 mg formulation, the maximum daily dose is 15 mg, with a total maximum dose of 2520 mg over the same treatment period. The active substance, **Upadacitinib**, is of chemical origin and is manufactured by ABBVIE DEUTSCHLAND GMBH & CO. KG.

In this study, participants who do not achieve an Eczema Area and Severity Index (EASI) 90 on the 15 mg dose after 12 weeks may have their dose escalated to 30 mg. Conversely, participants who achieve EASI 90 on the 30 mg dose after 12 weeks may have their dose reduced to 15 mg. The study does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the clinical trial will be assessed using the **Eczema Area and Severity Index (EASI)**, with a primary endpoint of achieving EASI 90 at Week 24. Secondary endpoints include achieving EASI 75/100 at Week 24, EASI 75/90/100 at Week 12, and additional measures such as the Worst Pruritus Numeric Rating Scale (NRS) and the Dermatology Life Quality Index (DLQI). These assessments will be conducted at specified timepoints, including Week 12 and Week 24, to evaluate the improvement in symptoms and quality of life for subjects with moderate to severe atopic dermatitis.

The trial involves two sub-studies: Sub-Study 1 (SS1) focuses on dose escalation to upadacitinib 30 mg once daily (QD) for subjects not achieving EASI 90 on 15 mg QD after 12 weeks, while Sub-Study 2 (SS2) evaluates dose reduction to 15 mg QD for those achieving EASI 90 on 30 mg QD after 12 weeks. The efficacy parameters will be collected and analyzed using validated scales and patient-reported outcomes to ensure accurate and reliable data. The study is designed to provide insights into the dose flexibility and treat-to-target approach for managing atopic dermatitis with upadacitinib.