Long-Term Safety Evaluation of Oral Povorcitinib in Patients with Hidradenitis Suppurativa, Prurigo Nodularis, or Vitiligo: A Phase 3b Rollover Study

The primary objective of this study is to continue evaluating the long-term **safety** of povorcitinib. This is clinically relevant as it aims to ensure the sustained safety profile of povorcitinib, a critical factor for its potential use in chronic conditions such as Hidradenitis Suppurativa, Prurigo Nodularis, and Vitiligo.

Secondary objectives include:

• For Hidradenitis Suppurativa (HS) indication: To continue evaluating the long-term efficacy of povorcitinib in participants with HS.
• For Vitiligo indication: To continue evaluating the long-term efficacy of povorcitinib in participants with vitiligo.
• For Prurigo Nodularis (PN) indication: To continue evaluating the long-term efficacy of povorcitinib in participants with PN.

The clinical trial involves a total of **1039 participants** who are being evaluated for the long-term safety of **povorcitinib**. The study population includes both male and female subjects, with an age range that encompasses both adults and adolescents. Participants were selected based on their completion of a prior Incyte-sponsored povorcitinib study, where they demonstrated compliance and received clinical benefit without safety or tolerability concerns. The trial includes individuals with medical conditions such as **Hidradenitis Suppurativa**, **Prurigo Nodularis**, and **Vitiligo**. The population is characterized by a mix of general health statuses, and it includes vulnerable groups. Participants are required to adhere to specific lifestyle considerations, such as avoiding pregnancy or fathering children during the study period. The selection criteria ensure that participants are willing and able to comply with the study protocol and procedures.

The clinical trial is designed as a **Phase 3b**, multicenter, rollover study to evaluate the long-term safety of **povorcitinib** in participants who have previously been enrolled in clinical trials for the same investigational product. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The trial is expected to commence recruitment on August 29, 2025, and is estimated to conclude by May 28, 2029, with a maximum treatment period of 36 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as having completed a prior **povorcitinib** study without safety concerns and demonstrating clinical benefit. Follow-up visits will be scheduled at regular intervals to monitor the primary endpoint, which is the incidence of treatment-emergent adverse events (TEAEs) in participants receiving **povorcitinib**. Secondary endpoints will vary based on the medical condition being treated, such as **hidradenitis suppurativa**, **prurigo nodularis**, or **vitiligo**, and will include assessments like ANdT count, F-VASI score, T-VASI score, Itch NRS score, and IGA-CPG-S score. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the long-term safety and efficacy of the treatment.

Participant involvement is expected to last up to 36 months, contingent upon adherence to the study protocol and procedures. Conditions that may lead to early termination from the study include non-compliance with protocol requirements, withdrawal of consent, or the occurrence of significant adverse events that compromise participant safety. The study aims to provide comprehensive data on the long-term safety profile of **povorcitinib** in treating the specified medical conditions.

The clinical trial involves the administration of **Povorcitinib**, a chemical entity developed by Incyte Corporation. Povorcitinib is provided in the form of a **tablet** and is intended for oral administration. The active substance in Povorcitinib is chemically synthesized and identified as 4-[3-(cyanomethyl)-3-(3',5'-dimethyl-1H,1'H-[4,4'-bipyrazol]-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(2S)-1,1,1-trifluoropropan-2-yl]benzamide. The pharmaceutical form of the medication is consistent across all participants, ensuring uniformity in administration. The maximum treatment period for Povorcitinib is set at 36 months, with the dosage measured in milligrams. The specific dosage and frequency of administration are determined based on the study protocol, although the maximum daily and total dose amounts are not specified in the provided data.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the long-term safety evaluation of Povorcitinib. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial does not include any pediatric formulations, and Povorcitinib is not classified as an orphan drug. The study is designed to continue the evaluation of Povorcitinib's safety profile, building on previous clinical trials involving this investigational medication.

The efficacy of **Povorcitinib** in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the incidence of treatment-emergent adverse events (TEAEs) reported in participants receiving **Povorcitinib**. Secondary endpoints vary based on the specific indication being studied. For the hidradenitis suppurativa (HS) indication, efficacy will be evaluated by the ANdT count of 0-2 at each visit. For the vitiligo indication, changes from baseline in the Facial Vitiligo Area Scoring Index (F-VASI) and Total Vitiligo Area Scoring Index (T-VASI) scores will be measured at each visit. For the prurigo nodularis (PN) indication, efficacy will be assessed by the Itch Numeric Rating Scale (NRS) score of 0 or 1 and the Investigator's Global Assessment of Clinical Condition and Pruritus Severity (IGA-CPG-S) score of 0 or 1 at each visit.