A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Efficacy and Safety Study of Povorcitinib (INCB054707) in Participants With Moderate to Severe Hidradenitis Suppurativa

The primary objective of this study is to evaluate the **efficacy** and safety of **povorcitinib** for the treatment of **hidradenitis suppurativa**, a chronic inflammatory skin condition characterized by painful nodules and abscesses. This objective is clinically relevant as it aims to determine the therapeutic potential of povorcitinib in managing symptoms and improving the quality of life for patients with moderate to severe forms of this condition.

Secondary objectives include:

• Further evaluation of the efficacy of povorcitinib.
• Assessment of the effect of povorcitinib in reducing the incidence of flares.
• Evaluation of the effect of povorcitinib in decreasing skin pain.
• Further evaluation of the effect of povorcitinib in decreasing skin pain.
• Evaluation of the effect of povorcitinib in improving fatigue.
• Assessment of the effect of povorcitinib on quality of life during the placebo-controlled and extension periods.
• Evaluation of the efficacy of povorcitinib during the extension period.
• Assessment of the maintenance of response during the extension period.

The clinical trial investigating the efficacy and safety of povorcitinib for the treatment of **hidradenitis suppurativa** includes a total of 212 participants. The study population comprises both male and female subjects, aged 18 years and older, who have been diagnosed with moderate to severe hidradenitis suppurativa for at least three months prior to the screening visit. Participants were selected based on their ability to comprehend and willingness to sign a written informed consent form, as well as their willingness and ability to comply with the study protocol and procedures. The trial includes individuals with a documented history of inadequate response to at least a three-month course of conventional systemic therapy for hidradenitis suppurativa. Participants are required to refrain from using topical and systemic antibiotics, diluted bleach baths, or topical antiseptic washes containing chlorhexidine gluconate or benzoyl peroxide on affected areas during the placebo-controlled period, with the exception of over-the-counter soap and water. The study population also includes vulnerable individuals, and all participants must agree to use contraception during the trial.

The clinical trial is designed to evaluate the **efficacy** and safety of **Povorcitinib** in participants with moderate to severe **Hidradenitis Suppurativa**. This is a Phase 3, double-blind, randomized, placebo-controlled study. The trial is expected to last until January 30, 2026, with recruitment starting on May 15, 2023. Participants will be randomly assigned to receive either Povorcitinib or a matching placebo, administered orally in tablet form. The maximum treatment period for participants is 54 weeks.

The study involves several key visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as a diagnosis of moderate to severe Hidradenitis Suppurativa for at least three months and a documented history of inadequate response to conventional systemic therapy. Participants must also agree to refrain from using certain topical and systemic treatments during the placebo-controlled period. Following the screening, participants will attend regular follow-up visits to monitor their response to treatment and assess any adverse effects. The primary endpoint is the proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12, with secondary endpoints including various measures of clinical response and quality of life at Weeks 12, 24, and 54.

The expected length of participant involvement is up to 54 weeks, with conditions for early termination including non-compliance with the study protocol or the occurrence of significant adverse events. The end-of-study visit will involve a comprehensive assessment of the participant's condition and overall response to the treatment. Throughout the trial, data will be collected and analyzed to determine the safety and efficacy of Povorcitinib in treating Hidradenitis Suppurativa, contributing valuable information to the field of dermatological therapeutics.

The clinical trial involves the administration of **Povorcitinib**, an experimental medication, in the form of oral tablets. Povorcitinib is chemically 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 Povorcitinib is a tablet, and it is administered orally. The maximum daily dose for one formulation is 75 mg, with a total maximum dose of 28,350 mg over a treatment period of 54 weeks. Another formulation of Povorcitinib is administered at a maximum daily dose of 45 mg, with a total maximum dose of 17,010 mg over the same treatment period. The active substance is of chemical origin, and the product is developed by Incyte Corporation.

The study also includes a **placebo** group, which receives a matching formulation of Povorcitinib oral tablets. The placebo is designed to mimic the experimental medication in appearance and administration route but does not contain the active substance. The placebo serves as a comparator treatment to evaluate the efficacy and safety of Povorcitinib in participants with moderate to severe hidradenitis suppurativa. The administration schedule and monitoring for compliance are consistent with those of the experimental medication to ensure the integrity of the double-blind, randomized, placebo-controlled study design.

The efficacy of the investigational medicinal product **Povorcitinib** in the treatment of moderate to severe **Hidradenitis Suppurativa** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants who achieve Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12. Secondary endpoints include the proportion of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 12, the proportion of participants with flare by Week 12, and the proportion of participants who achieve Skin Pain NRS30 at Week 12 among those with a baseline Skin Pain NRS score of 3 or higher. Additional secondary endpoints involve changes in Dermatology Life Quality Index (DLQI) scores, abscess and inflammatory nodule counts, and Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scores at various timepoints, including Weeks 12, 24, and 54.

Data collection will occur at specified intervals, with efficacy parameters being measured at baseline and subsequent visits. The analysis will focus on the mean and percentage changes from baseline in various clinical measures, as well as the maintenance of HiSCR or greater response during the extended period. These assessments will utilize validated scales and patient-reported outcomes to ensure accuracy and reliability in measuring the therapeutic impact of Povorcitinib. The trial is designed to provide comprehensive data on the efficacy of the treatment over a maximum treatment period of 54 weeks.