Evaluation of Upadacitinib Efficacy, Safety, and Tolerability in Adults and Adolescents with Non-Segmental Vitiligo Eligible for Systemic Therapy

The primary objective of this study is to evaluate the **efficacy**, safety, and tolerability of upadacitinib in adult and adolescent subjects with non-segmental vitiligo (NSV) who are eligible for systemic therapy. This is clinically relevant as it aims to provide a potential therapeutic option for individuals with NSV, a condition characterized by the loss of skin pigmentation, which can significantly impact quality of life.

Secondary objectives include:

• Determining if the proportion of subjects achieving each of the ranked secondary binary endpoints with upadacitinib 15 mg is greater than those treated with placebo.
• Assessing the percent change from baseline in F-VASI (Facial Vitiligo Area Scoring Index) in subjects treated with upadacitinib 15 mg compared to placebo at Week 24.
• Evaluating the percent change from baseline in T-VASI (Total Vitiligo Area Scoring Index) in subjects treated with upadacitinib 15 mg compared to placebo at Week 48.

The clinical trial involves a total of **381 participants** diagnosed with **non-segmental vitiligo** (NSV). The study population includes both male and female subjects, comprising adults and adolescents aged 12 years and older. Participants are required to have a body weight of at least 30 kg if they are between 12 and 18 years of age. The trial population was selected based on their eligibility for systemic therapy and a documented clinical diagnosis of NSV. Participants must have demonstrated either a failure of at least one topical corticosteroid or calcineurin inhibitor for vitiligo, or signs of actively progressing vitiligo. All subjects are judged to be in good health as determined by the Principal Investigator, based on screening assessments and medical history. The trial includes a vulnerable population, and pregnancy testing is mandatory for female subjects of childbearing potential to ensure safety. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy**, safety, and tolerability of **upadacitinib** in adult and adolescent subjects with non-segmental vitiligo who are eligible for systemic therapy. This is a Phase 3, randomized, placebo-controlled, double-blind study. The trial is expected to commence recruitment on April 1, 2024, and conclude by February 7, 2028. Participants will be randomly assigned to receive either upadacitinib or a placebo, administered as a modified-release tablet for oral use. The maximum daily dose of upadacitinib is 15 mg, with a total treatment period of up to 160 days.

The study will include several key visits: an initial screening visit to confirm eligibility, baseline assessments, and regular follow-up visits to monitor progress and safety. The primary endpoint is the achievement of a ≥50% reduction in T-VASI from baseline at Week 48. Secondary endpoints include various measures of improvement in vitiligo severity and patient-reported outcomes at different time points. The expected duration of participant involvement is approximately 48 weeks, with conditions for early termination including adverse events, non-compliance with the study protocol, or withdrawal of consent.

Inclusion criteria require participants to be at least 12 years old, with a body weight of at least 30 kg for those under 18, and a documented clinical diagnosis of non-segmental vitiligo. Participants must have failed previous topical treatments or have actively progressing vitiligo. Female participants of childbearing potential must have negative pregnancy tests at screening and baseline. The study aims to provide comprehensive data on the potential benefits and risks of upadacitinib in treating non-segmental vitiligo, contributing to the understanding of its therapeutic profile.

The clinical trial involves the administration of **Upadacitinib**, a modified-release tablet, as the experimental medication. Upadacitinib is a chemical substance with the active ingredient identified as UPADACITINIB. The pharmaceutical form is a modified-release tablet, and the medication is administered orally. The maximum daily dose is 15 mg, with a total maximum dose of 16,800 mg over a treatment period of 160 days. The medication is provided by AbbVie Deutschland GmbH & Co. KG. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this study. The placebo is designed to match the experimental medication in appearance and administration route, which is oral. The placebo serves as a control to evaluate the efficacy and safety of Upadacitinib in treating non-segmental vitiligo in adult and adolescent subjects eligible for systemic therapy. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of outcomes.

The efficacy of the clinical trial evaluating **Upadacitinib** in adult and adolescent subjects with non-segmental vitiligo (NSV) will be assessed using specific primary and secondary endpoints. The primary endpoints include the achievement of T-VASI 50, defined as a ≥ 50% reduction in T-VASI from baseline, and F-VASI 75, defined as a ≥ 75% reduction in F-VASI from baseline, both measured at Week 48. Secondary endpoints encompass a range of measures, including the achievement of F-VASI 50 and F-VASI 75 at Week 48 and Week 24, respectively, as well as the percent change from baseline in F-VASI at Week 24 and T-VASI at Week 48. Additional secondary endpoints include the achievement of F-VASI 90, a VNS score of "A lot less noticeable (4)" or "No longer noticeable (5)," and a PaGIC-V and PhGIC-V score of "Much better (1)" at Week 48.

The efficacy parameters will be collected and analyzed at specified timepoints, including Week 24 and Week 48, using validated scales and patient-reported outcomes. The trial is designed to ensure rigorous assessment of the treatment's impact on NSV, with a focus on both the extent of skin repigmentation and patient perception of improvement. The study will adhere to a double-blind, placebo-controlled methodology to maintain objectivity and reliability in the evaluation of **Upadacitinib**'s efficacy.