Long-Term Safety and Efficacy Evaluation of Povorcitinib in Moderate to Severe Hidradenitis Suppurativa: A Phase 3 Double-Blind Study

The primary objective of this Phase 3 double-blind study is to evaluate the long-term **safety** of **povorcitinib** in participants with moderate to severe **Hidradenitis Suppurativa**. This is clinically relevant as it aims to ensure that the therapeutic benefits of povorcitinib do not come with unacceptable adverse effects over extended use, which is crucial for chronic conditions like Hidradenitis Suppurativa.

Secondary objectives include: - To further evaluate the long-term safety of povorcitinib. - To evaluate the long-term efficacy of povorcitinib. - To assess the long-term effect of povorcitinib in reducing the incidence of flares. - To evaluate the effect of povorcitinib on quality of life (QoL). - To evaluate the effect of povorcitinib on lesion counts.

These secondary objectives are significant as they provide a comprehensive understanding of the drug's impact on disease progression, patient quality of life, and overall treatment outcomes, which are essential for optimizing therapeutic strategies in managing Hidradenitis Suppurativa.

The clinical trial involves a total of **257 participants** diagnosed with **Hidradenitis Suppurativa**, a chronic skin condition. The study population includes both male and female subjects, with an age range encompassing adults and adolescents. Participants were selected based on their completion of a 54-week treatment period in a preceding study without any safety concerns, as assessed by the investigator. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and compliance. Participants are required to demonstrate compliance with study protocols and procedures, including the use of contraception as specified. The trial aims to evaluate the long-term safety of povorcitinib, with no specific lifestyle considerations such as diet or physical activity mentioned in the selection criteria.

The clinical trial is designed to evaluate the long-term safety and efficacy of **povorcitinib** in participants with moderate to severe **hidradenitis suppurativa**. This is a Phase 3, double-blind, randomized, controlled study. The trial is expected to commence recruitment on July 4, 2024, and conclude by January 13, 2027. Participants will be involved in the study for a maximum treatment period of 54 weeks, contingent upon their completion of the originating parent study without safety concerns. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes.

Participants will be required to attend scheduled visits throughout the trial duration, where they will undergo assessments to monitor the proportion of treatment-emergent adverse events (TEAEs) and other secondary endpoints such as the achievement of HiSCR (Hidradenitis Suppurativa Clinical Response) at various thresholds. The study will also evaluate changes in quality of life scores using the HiSQoL and DLQI instruments. Participants must demonstrate compliance with the study protocol and procedures, including the use of contraception as specified. Conditions that may lead to early termination from the study include the occurrence of serious TEAEs or non-compliance with study requirements. The investigational product, povorcitinib, will be administered orally in tablet form, with the dosage and administration closely monitored throughout the trial.

The clinical trial involves the administration of **Povorcitinib**, an investigational medication formulated as a **tablet**. 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 medication is administered **orally**. The trial includes two treatment periods with maximum durations of 52 and 54 weeks, respectively. The specific dosage and frequency of administration are not detailed in the provided data. The investigational product is not a pediatric formulation and is not classified as an orphan drug. The sponsor of the trial is Incyte Corporation, and the product is identified by the sponsor product code INCB054707.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment, although specific details are not provided in the data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to evaluate the long-term safety and efficacy of Povorcitinib in participants with moderate to severe **Hidradenitis Suppurativa**. The study is conducted under a double-blind design to maintain the integrity of the results.

The efficacy of the investigational medicinal product **Povorcitinib** in the treatment of moderate to severe **Hidradenitis Suppurativa** will be assessed through a series of predefined endpoints. The primary efficacy endpoint is the proportion of participants with treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints include the proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at each visit, defined as at least a 50% reduction from baseline in the total abscess and nodule (AN) count, with no increase in abscess or draining tunnel count. Additional secondary endpoints include HiSCR75, HiSCR90, and HiSCR100, which represent 75%, 90%, and 100% reductions from baseline, respectively.

Other secondary endpoints involve the proportion of participants experiencing a flare, defined as at least a 25% increase in AN count with a minimum increase of 2 ANs relative to Week 54, and the time to first flare. Quality of life measures will be evaluated using the Hidradenitis Suppurativa Quality of Life (HiSQoL) score and the Dermatology Life Quality Index (DLQI), with changes from baseline assessed at each visit. The HiSQoL is a 17-item, disease-specific instrument with a 7-day recall period, while the DLQI is a skin disease-specific questionnaire. Both instruments aim to evaluate the impact of the disease on health-related quality of life.

Additional assessments include the proportion of participants with no increase in AN count, ANdT count (total sum of abscess, inflammatory nodule, and draining tunnel), and draining tunnel count relative to Week 54 at each visit. The study will also measure the proportion of participants with a total AN count of 0, 1, or 2, and a total ANdT count of 0, 1, or 2 at each visit. These efficacy parameters will be collected and analyzed at each scheduled visit throughout the trial duration, providing comprehensive data on the long-term efficacy of Povorcitinib in this patient population.