Efficacy and Safety Evaluation of Subcutaneous Sonelokimab in Adults with Moderate to Severe Hidradenitis Suppurativa: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to demonstrate the **efficacy** of sonelokimab compared with placebo in achieving HiSCR75 over 16 weeks of treatment in participants with moderate to severe **hidradenitis suppurativa** (HS). This is clinically relevant as achieving HiSCR75, a 75% reduction in inflammatory nodules and abscesses, is a significant indicator of treatment success in HS, a chronic and painful skin condition.

Secondary objectives include:

• Evaluating the safety and tolerability of sonelokimab over 52 weeks of treatment in participants with moderate to severe HS.
• Assessing the efficacy of sonelokimab compared with placebo based on other clinical measures of disease activity over 16 weeks of treatment.
• Assessing the change from baseline to Week 52 in efficacy measures in participants with moderate to severe HS.

The clinical trial involves a total of **108 participants** diagnosed with **hidradenitis suppurativa (HS)**, a chronic inflammatory skin condition. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with moderate to severe HS. Participants were selected based on their inadequate response to systemic antibiotics or intolerance to such treatments, as determined by the investigator. The trial does not include any vulnerable populations. Participants are required to maintain a stable dose of antibiotics if enrolled in the antibiotic cohort. Lifestyle considerations such as diet and physical activity are not specified. The trial ensures that female participants of childbearing potential use highly effective contraception methods, and male participants agree to use condoms and refrain from sperm donation during and after the study period. The selection criteria emphasize the ability to provide informed consent and comply with study requirements.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of subcutaneous **sonelokimab** in adult participants with moderate to severe **hidradenitis suppurativa**. The trial is set to commence recruitment on September 1, 2024, and is expected to conclude by April 30, 2026. The primary objective is to demonstrate the efficacy of sonelokimab compared to placebo, with the primary endpoint being the percentage of participants achieving a 75% improvement in the Hidradenitis Suppurativa Clinical Response (HiSCR) score at Week 16. Secondary endpoints include the assessment of treatment-emergent adverse events, serious adverse events, and other clinical parameters.

Participants will be involved in the study for a maximum treatment period of 48 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor treatment response and safety, and a final end-of-study visit. The inclusion criteria require participants to be at least 18 years old, have a confirmed diagnosis of hidradenitis suppurativa, and have had an inadequate response to systemic antibiotics. Female participants of childbearing potential must use highly effective contraception methods, and male participants must agree to use condoms during the study period.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study will utilize a placebo as a sterile solution in a single-use prefilled syringe for subcutaneous administration, ensuring the blinding of both participants and investigators. The trial's design and methodology adhere to rigorous scientific standards to ensure the reliability and validity of the results.

**Sonelokimab** is the experimental medication being evaluated in this clinical trial. It is administered as a **subcutaneous injection** and is formulated as an injection. The active substance, sonelokimab, is a nanobody that inhibits **IL-17A** and **IL-17F**, and is classified as a protein of other origin. The maximum daily dose of sonelokimab is 120 mg/ml, with a total maximum dose of 1620 mg/ml over the treatment period. The treatment duration is set for a maximum of 48 weeks. The administration schedule and participant compliance are monitored throughout the study to ensure adherence to the dosing regimen.

The study also includes a **placebo** as a comparator treatment. The placebo is a sterile solution provided in a single-use prefilled syringe intended for subcutaneous administration. It serves as a control to evaluate the efficacy and safety of sonelokimab in participants with moderate to severe **hidradenitis suppurativa**. The placebo is administered in a manner identical to the experimental treatment to maintain the double-blind nature of the study. Compliance with the placebo administration is similarly monitored to ensure the integrity of the trial results.

The efficacy of the investigational product, **Sonelokimab**, will be assessed in a phase 3, randomized, double-blind, placebo-controlled, multicenter study involving adult participants with moderate to severe **Hidradenitis Suppurativa**. The primary endpoint for evaluating efficacy is the percentage of participants achieving a 75% improvement in the Hidradenitis Suppurativa Clinical Response (HiSCR) score at Week 16. Secondary endpoints include the percentage of participants achieving a 50% improvement in HiSCR score at Week 16, absolute change in the International Hidradenitis Suppurativa Severity Score System (IHS4) score at Week 16, and the percentage of participants achieving a Dermatology Life Quality Index (DLQI) total reduction of ≥4 at Week 16 among those with a baseline DLQI ≥4. Additionally, the study will assess the percentage of participants achieving a ≥30% reduction and a ≥2 unit reduction at Week 16 in the Numerical Rating Scale (NRS30) for pain in the Patient Global Assessment (PGA) among those with a baseline NRS ≥3, as well as a ≥3-unit reduction at Week 16 in the NRS for pain in PGA among participants with a baseline NRS ≥3.