A Phase 3b/4 Randomized, Open-label, Efficacy Assessor-Blinded Study, to Evaluate the Efficacy and Safety of Upadacitinib for the Treatment of Adult Subjects with Moderate to Severe Atopic Dermatitis and Inadequate Response to Dupilumab (SWITCH-UP)

The primary objective is to assess the efficacy and safety of upadacitinib compared with dupilumab as per its label in adult subjects with atopic dermatitis who have demonstrated inadequate response to dupilumab. This objective addresses a clinically relevant population of patients with moderate to severe atopic dermatitis who fail to achieve adequate disease control with dupilumab therapy, evaluating whether switching to upadacitinib provides improved therapeutic outcomes and an acceptable safety profile in this treatment-refractory population.

The clinical trial enrolled a total of **150 participants** diagnosed with **atopic dermatitis**. The study population consisted of **adult subjects** of both **male** and **female** gender. Participants were selected based on inadequate response to **dupilumab** treatment after at least 4 months of current use. Key disease activity criteria at baseline included an **Eczema Area and Severity Index (EASI) score** of 12 or greater, a **Validated Investigator's Global Assessment for AD (vIGA-AD) score** of 3 or greater, **body surface area (BSA)** involvement of 10% or greater in the majority of subjects, and a baseline weekly average of daily **Worst Pruritus-Numerical Rating Scale (WP-NRS)** of 4 or greater. All participants had chronic atopic dermatitis with symptom onset at least 3 years prior to baseline and met **Hanifin and Rajka criteria**. Regarding lifestyle considerations, participants were required to apply a **topical emollient** twice daily for at least 7 days before baseline and throughout the study duration. The trial did not include vulnerable populations.

This is a Phase 3b/4, randomized, open-label, efficacy assessor-blinded clinical trial evaluating the efficacy and safety of **upadacitinib** compared with **dupilumab** in adult participants with moderate to severe **atopic dermatitis** who have demonstrated inadequate response to dupilumab treatment. The study involves the administration of upadacitinib as a **modified-release tablet** for **oral use** at maximum daily doses of either 15 mg or 30 mg, with a maximum total dose of 3360 mg or 6720 mg respectively, over a treatment period of up to 32 weeks. The comparator, dupilumab, is administered via **subcutaneous injection** at a maximum daily dose of 300 mg, with a maximum total dose of 4800 mg over the same 32-week treatment period. The active substance in the investigational product is upadacitinib, a chemical substance, while dupilumab is a protein-based substance. The primary objective of the trial is to assess the efficacy and safety of upadacitinib compared with dupilumab as per its label in adult subjects with inadequate response to dupilumab.

Participants eligible for enrollment must meet specific disease activity criteria at the baseline visit, including an **Eczema Area and Severity Index** (EASI) score of at least 12, a validated Investigator's Global Assessment for AD (**vIGA-AD**) score of at least 3, body surface area involvement of at least 10% in a majority of subjects, and a baseline weekly average of daily Worst Pruritus-Numerical Rating Scale (**WP-NRS**) of at least 4. Participants must have demonstrated inadequate response to dupilumab treatment after at least 4 months of current use and must have applied a topical emollient twice daily for at least 7 days before the baseline visit. Additionally, participants must have chronic atopic dermatitis with onset of symptoms at least 3 years prior to baseline and meet Hanifin and Rajka criteria. The baseline weekly average of daily WP-NRS is calculated from 7 consecutive days immediately preceding the baseline visit, with a minimum of 4 daily scores out of 7 days required.

The primary endpoint of the study is the percentage of participants who achieve at least a 90% reduction in Eczema Area and Severity Index from baseline (**EASI 90**) at Week 8. Secondary endpoints include the percentage of participants who achieve a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 8, the percentage of participants who simultaneously achieve EASI 90 and WP-NRS 0/1 at Week 8, and the percentage of participants achieving WP-NRS 0/1 at Week 4. The trial is designed to provide comprehensive efficacy and safety data for upadacitinib in this specific patient population with inadequate response to existing treatment.

The estimated recruitment start date for the trial is March 1, 2026, with an estimated end date of June 9, 2027. Participant involvement spans the duration of the treatment period, which is up to 32 weeks, with scheduled study visits for screening, baseline assessment, and follow-up evaluations at predetermined intervals, including assessments at Week 4 and Week 8 for primary and secondary endpoint measurements. The end-of-study visit occurs upon completion of the 32-week treatment period or upon early termination. Conditions that may lead to early termination from the study are not explicitly detailed in the available data, but standard clinical trial protocols typically include criteria such as adverse events, withdrawal of consent, protocol violations, or investigator discretion based on participant safety considerations.

**Upadacitinib** (sponsor product code ABT-494) is administered as a **modified-release tablet** for **oral use**. Two dosage regimens are evaluated in this clinical trial. The first regimen consists of **15 mg** administered once daily, with a maximum daily dose of 15 mg and a maximum total dose of **3360 mg** over the treatment period. The second regimen consists of **30 mg** administered once daily, with a maximum daily dose of 30 mg and a maximum total dose of **6720 mg** over the treatment period. The **active substance** is upadacitinib, which is of chemical origin. The maximum treatment period for both upadacitinib dosing regimens is **32 weeks**.

**Dupilumab** is administered as a **comparator treatment** in this study. The pharmaceutical form is an **injection** administered via **subcutaneous injection**. The maximum daily dose is **300 mg**, with a maximum total dose of **4800 mg** over the treatment period. The active substance is dupilumab, which is a protein of biological origin. Dupilumab is administered according to its approved label in adult subjects with **moderate to severe atopic dermatitis**. The maximum treatment period for dupilumab is **32 weeks**.

Efficacy will be assessed using multiple parameters to evaluate treatment response in adults with moderate to severe **atopic dermatitis** who have demonstrated inadequate response to dupilumab. The primary efficacy endpoint is the proportion of participants who achieve at least a 90% reduction in **Eczema Area and Severity Index** from baseline (EASI 90) at Week 8. Secondary efficacy endpoints include the percentage of participants who achieve a **Worst Pruritus Numerical Rating Scale** score of 0 or 1 (WP-NRS 0/1) at Week 8, the proportion of participants who simultaneously achieve both EASI 90 and WP-NRS 0/1 at Week 8, and the percentage of participants achieving WP-NRS 0/1 at Week 4. Disease activity at baseline will be characterized by EASI score of at least 12, **Validated Investigator's Global Assessment for Atopic Dermatitis** (vIGA-AD) score of at least 3, body surface area involvement of at least 10% in a majority of subjects, and baseline weekly average of daily WP-NRS of at least 4. Efficacy assessments will be conducted at specified timepoints including Week 4 and Week 8 to evaluate treatment outcomes and disease improvement.