Efficacy and Safety of Povorcitinib in a 52-Week, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial for Adult Nonsegmental Vitiligo

The primary objective of this study is to compare the **efficacy** of povorcitinib to placebo at Week 52 in adult participants with nonsegmental vitiligo. This objective is clinically relevant as it aims to evaluate the potential of povorcitinib as a therapeutic option for nonsegmental vitiligo, a condition characterized by the loss of skin pigmentation, which can significantly impact patients' quality of life.

Secondary objectives include:

• Further comparing the efficacy of povorcitinib to placebo at Week 52 in adult participants with nonsegmental vitiligo.
• Comparing participants' perception of treatment response for povorcitinib versus placebo at Week 52.

The clinical trial involves a total of **241 participants** diagnosed with **nonsegmental vitiligo**. The study population includes both male and female adults aged 18 years and older. Participants were selected based on their ability to comprehend and sign an informed consent form, as well as their clinical diagnosis of nonsegmental vitiligo. The trial population is required to discontinue all treatments for vitiligo from the screening phase through the final safety follow-up visit. Participants must also agree to avoid pregnancy or fathering children during the study period. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and compliance with the study protocol. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Povorcitinib** in adult participants with nonsegmental **vitiligo**. The trial is set to last for 52 weeks, with an estimated recruitment start date in March 2024 and an estimated end date in June 2027. Participants will be randomly assigned to receive either Povorcitinib or a placebo, administered orally in tablet form. The primary objective is to compare the efficacy of Povorcitinib to placebo at Week 52, with the primary endpoint being the proportion of participants achieving a 75% or greater improvement from baseline in the Face Vitiligo Area Scoring Index (F-VASI75) at Week 52.

The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and a final end-of-study visit. During the screening visit, participants will be assessed for their ability to comprehend and sign the informed consent form, be at least 18 years of age, have a clinical diagnosis of nonsegmental vitiligo, and meet other specific criteria. Follow-up visits will occur periodically throughout the 52-week trial to assess efficacy and safety outcomes, including photography for documentation. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced during the trial.

Participant involvement is expected to last for the entire 52-week duration of the trial. However, conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that pose a risk to the participant's health. The trial aims to provide valuable data on the potential benefits of Povorcitinib for individuals with nonsegmental vitiligo, contributing to the understanding and management of this condition.

The clinical trial involves the administration of **Povorcitinib**, an experimental medication, to evaluate its efficacy and safety in participants with nonsegmental vitiligo. **Povorcitinib** is provided in the form of a **tablet** and is administered **orally**. The active substance in this medication is **povorcitinib**, a chemical compound developed by Incyte Corporation. The dosing schedule for **Povorcitinib** is determined by the study protocol, with a maximum treatment period of 104 weeks. The specific dosage in milligrams is not detailed in the provided data. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy of **Povorcitinib**. The placebo is designed to mimic the experimental medication in appearance and administration route but does not contain the active substance. The placebo is administered **orally** in a form that is consistent with the **tablet** formulation of **Povorcitinib**. The use of a placebo control 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 Povorcitinib in the treatment of **nonsegmental vitiligo** will be assessed in a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants achieving a ≥ 75% improvement from baseline in the Face Vitiligo Area Scoring Index (F-VASI75) at Week 52. Secondary endpoints include the percentage change from baseline in the Total Body Vitiligo Area Scoring Index (T-VASI) at Week 52, the proportion of participants achieving ≥ 50% improvement from baseline in T-VASI (T-VASI50) at Week 52, the proportion of participants achieving ≥ 75% improvement from baseline in T-VASI (T-VASI75) at Week 52, and the proportion of participants achieving a Vitiligo Noticeability Scale (VNS) score of "4 – A lot less noticeable" or "5 – No longer noticeable" at Week 52.