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

The primary objective of this study is to evaluate the **efficacy** and safety of povorcitinib for the treatment of moderate to severe **hidradenitis suppurativa**. This is clinically relevant as hidradenitis suppurativa is a chronic inflammatory skin condition that significantly impacts patients' quality of life, and effective treatments are limited. Assessing the efficacy and safety of povorcitinib could provide a new therapeutic option for managing this condition.

Secondary objectives include:

• Further evaluating the efficacy of povorcitinib.
• Assessing the effect of povorcitinib in reducing the incidence of flares.
• Evaluating the effect of povorcitinib in decreasing skin pain.
• Assessing the effect of povorcitinib in improving fatigue.
• Evaluating the effect of povorcitinib on quality of life during the placebo-controlled and extension periods.
• Evaluating the efficacy of povorcitinib during the extension period.
• Assessing 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 309 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 have hidradenitis suppurativa lesions in at least two distinct anatomical areas, with at least one area being at Hurley Stage II or III. The trial population is characterized by a vulnerable population selection, and participants have agreed to refrain from using certain topical and systemic antibiotics, as well as specific antiseptic washes, during the placebo-controlled period. Additionally, participants have agreed to use contraception throughout the study duration.

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 the investigational product or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the study's double-blind nature.

The trial will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age, diagnosis of moderate to severe **Hidradenitis Suppurativa** for at least three months, and a documented history of inadequate response to conventional systemic therapy. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse events. The primary endpoint is the proportion of participants achieving **Hidradenitis Suppurativa Clinical Response** (HiSCR) at Week 12. Secondary endpoints include various measures of clinical response and quality of life at Weeks 12, 24, and 54.

Participant involvement is expected to last up to 54 weeks, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The study aims to provide comprehensive data on the safety and efficacy of **Povorcitinib** in treating this chronic skin condition, contributing valuable insights into its potential as a therapeutic option.

The clinical trial involves the administration of **Povorcitinib** (INCB054707), an investigational 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 trial includes two dosage regimens: a maximum daily dose of 75 mg and a maximum daily dose of 45 mg, with a total treatment period of up to 54 weeks. The total maximum dose for the 75 mg regimen is 28,350 mg, while for the 45 mg regimen, it is 17,010 mg. The medication is provided by Incyte Corporation and is not a pediatric formulation.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, randomized, placebo-controlled study. The placebo is designed to match the formulation of Povorcitinib oral tablets to ensure blinding. The placebo is administered in the same manner as the active drug, orally, and in tablet form. The use of a placebo allows for the assessment of the efficacy and safety of Povorcitinib in participants with moderate to severe **hidradenitis suppurativa**.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen. The trial aims to evaluate the efficacy and safety of Povorcitinib, with the primary objective being the treatment of hidradenitis suppurativa. The study is conducted under the authorization number DE_BW_01_MIA_2022_0034, and the investigational product is classified as a chemical substance.

The efficacy of **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 various clinical parameters such as abscess count, inflammatory nodule count, and draining tunnel count, measured as both mean and percentage changes from baseline at each visit.

These efficacy parameters will be collected and analyzed at specified timepoints, including Weeks 12, 24, and 54, using validated scales and patient-reported outcomes. The study will also evaluate the maintenance of HiSCR and HiSCR75 responses during the extended period (EXT). The assessment tools include the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) score and the Dermatology Life Quality Index (DLQI) score, which will be used to measure changes in fatigue and quality of life, respectively. The trial is designed to provide a comprehensive evaluation of the therapeutic benefits of **Povorcitinib** over a maximum treatment period of 54 weeks.