Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Evaluating Izokibep Efficacy and Safety in Moderate to Severe Hidradenitis Suppurativa

The primary objective of this study is to evaluate the **efficacy** of **izokibep** compared with placebo in subjects with moderate to severe **Hidradenitis Suppurativa**. This is measured by the percentage of subjects achieving a Hidradenitis Suppurativa Clinical Response (HiSCR75) at Week 12. The clinical relevance of this objective lies in its potential to provide a new therapeutic option for patients suffering from this chronic and painful skin condition, which currently has limited effective treatments.

Secondary objectives include demonstrating the efficacy of izokibep compared with placebo as measured by:

• Percentage of subjects achieving HiSCR90, HiSCR100, and HiSCR50 at Week 12
• Percentage of subjects experiencing at least one disease flare through 12 weeks of treatment
• Dermatology Life Quality Index (DLQI)
• Percentage of subjects with baseline Hurley Stage II achieving an abscess and inflammatory nodule (AN) count of 0, 1, or 2 at Week 12
• Percentage of subjects achieving at least a 3-point reduction from baseline in the Numerical Rating Scale (NRS) for Patient Global Assessment of Skin Pain at its worst among subjects with baseline NRS ≥ 4

The clinical trial involves a total of **182 participants** diagnosed with **Hidradenitis Suppurativa**. The study population includes both male and female subjects, aged 18 years and above, with no upper age limit specified. Participants were selected based on the presence of hidradenitis suppurativa lesions in at least two distinct anatomic areas, with one area being classified as Hurley Stage II or III. The trial population includes individuals who have had an inadequate response to oral antibiotics, or who have experienced recurrence, intolerance, or contraindications to such treatments. All participants were required to have a negative TB test at screening. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations may be in place to ensure the safety and ethical treatment of participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **Izokibep** in subjects with moderate to severe **Hidradenitis Suppurativa**. The trial is a Phase 3 study, with an estimated recruitment start date of December 6, 2023, and an estimated end date of December 17, 2025. The primary objective is to demonstrate the efficacy of Izokibep compared to placebo, measured by the percentage of subjects achieving HiSCR75 at Week 12. Secondary endpoints include HiSCR90, HiSCR100, and HiSCR50 at Week 12, as well as changes in DLQI and AN count, among others.

Participants will be involved in the study for a maximum treatment period of 51 weeks. The study includes several key visits: an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, presence of **Hidradenitis Suppurativa** lesions, and previous treatment responses; follow-up visits to monitor progress and collect data on primary and secondary endpoints; and an end-of-study visit to assess overall outcomes and safety. The inclusion criteria require subjects to be 18 years or older, with specific lesion characteristics and a history of inadequate response to oral antibiotics.

Participants may be terminated early from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The study employs a **subcutaneous** route of administration for Izokibep, with a maximum daily dose of 160 mg. The trial is not categorized as low intervention, and it is not an orphan drug study. The trial's design ensures rigorous assessment of the investigational product's efficacy and safety, contributing valuable data to the understanding and treatment of **Hidradenitis Suppurativa**.

The clinical trial involves the administration of **Izokibep**, an experimental medication, to evaluate its efficacy and safety in subjects with moderate to severe **Hidradenitis Suppurativa**. Izokibep is provided as a **solution for injection** and is administered via the **subcutaneous** route. The maximum daily dose is 160 mg, with a total maximum dose of 160 mg over the treatment period. The treatment duration is set for a maximum of 51 weeks. Izokibep is a protein-based substance, specifically categorized under "Protein - Other," and is developed by ACELYRIN, INC. The primary objective of the trial is to assess the percentage of subjects achieving HiSCR75 at Week 12.

In addition to the experimental treatment, a **placebo** is used as a comparator in this randomized, double-blind, placebo-controlled study. The placebo is designed to match the experimental treatment in appearance and administration method, ensuring the blinding of both participants and investigators. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the true efficacy of Izokibep. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the outcomes of the treatment.

The efficacy of Izokibep in the treatment of moderate to severe **Hidradenitis Suppurativa** will be assessed in a randomized, double-blind, placebo-controlled, multicenter, Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the percentage of subjects achieving HiSCR75 at Week 12. Secondary endpoints include HiSCR90, HiSCR100, and HiSCR50 at Week 12, as well as the occurrence of HS flares through Week 12. Additional secondary endpoints involve changes in the Dermatology Life Quality Index (DLQI) from baseline to Week 12, achieving an AN count of 0, 1, or 2 at Week 12, and changes from baseline in the Numerical Rating Scale (NRS) for Patient Global Assessment of Skin Pain at its worst at Week 12. Safety assessments will include the monitoring of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), along with laboratory values and vital signs collected at specified timepoints.