A Multicenter, Double-Blind, Randomized Withdrawal Study of Subcutaneous Secukinumab for Long-Term Efficacy and Safety in Moderate to Severe Hidradenitis Suppurativa

The primary objective of this study is to demonstrate the **efficacy** of secukinumab (300 mg every 4 weeks or 300 mg every 2 weeks) in subjects with moderate to severe **hidradenitis suppurativa** (HS) who were HiSCR responders at Week 52 of the core studies. The focus is on assessing the loss of response by Week 104 compared to placebo. This is clinically relevant as it evaluates the sustained effectiveness of secukinumab in maintaining therapeutic response in HS patients, which is crucial for long-term disease management.

Secondary objectives include assessing the long-term **safety** and tolerability of secukinumab in subjects with moderate to severe HS. This will be evaluated through monitoring adverse events, abnormal laboratory values, and vital signs. These assessments are important to ensure that the treatment remains safe and well-tolerated over an extended period, providing comprehensive insights into its risk-benefit profile.

The clinical trial involves a total of **349 participants** diagnosed with **hidradenitis suppurativa**, a chronic inflammatory skin condition. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults. Participants were selected based on their completion of a 52-week treatment period in prior core studies and their receipt of secukinumab during the Treatment Period 2 of these studies. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. The study does not specify particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the long-term efficacy, safety, and tolerability of **secukinumab** in subjects with moderate to severe **hidradenitis suppurativa**. The trial involves a **randomized withdrawal** extension study, where participants who have shown a response to secukinumab in previous core studies will be assessed for loss of response when switched to a placebo. The primary objective is to determine the time to loss of response up to Week 104 in subjects who were HiSCR responders at Week 52 in the core studies. The trial is expected to run until May 2026, with recruitment having started in April 2020.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of the core study treatment period and prior secukinumab treatment. Follow-up visits will be scheduled regularly to monitor the participants' response to the treatment, assess adverse events, and collect laboratory values and vital signs. The end-of-study visit will conclude the trial for each participant, providing a final assessment of their condition and any long-term effects of the treatment.

The expected length of participant involvement is approximately 208 weeks, contingent upon their continued eligibility and response to the treatment. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to adhere to the study protocol. Participants will receive either secukinumab or a placebo administered subcutaneously, with the dosing regimen being either 300 mg every four weeks or every two weeks, depending on the study arm. The trial aims to provide valuable insights into the management of hidradenitis suppurativa and the potential benefits of continuous versus interrupted treatment regimens.

The clinical trial involves the administration of **Secukinumab**, a solution for injection, as the experimental medication. Secukinumab is administered subcutaneously at a dosage of 300 mg. The dosing schedule includes administration every four weeks (q4w) or every two weeks (q2w), depending on the study protocol. The maximum daily dose is 300 mg, with a total maximum dose of 31,200 mg over the treatment period. The treatment period extends up to 208 weeks. Secukinumab is a protein-based therapeutic agent, specifically classified under the origin "Protein - Other." The study aims to evaluate the long-term efficacy, safety, and tolerability of Secukinumab in subjects with moderate to severe **hidradenitis suppurativa** who were HiSCR responders at Week 52 of the core studies.

The trial also includes a **placebo** comparator, which is a solution for injection in a pre-filled syringe, designed to match the appearance and administration route of Secukinumab. The placebo is administered subcutaneously, following the same dosing schedule as the experimental medication, either every four weeks or every two weeks. The placebo serves as a control to assess the efficacy of Secukinumab by comparing the loss of response by Week 104 in subjects receiving the active treatment versus those receiving the placebo. The use of a placebo is critical in maintaining the double-blind nature of the study, ensuring unbiased results.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the time to loss of response up to Week 104 during the Randomized Withdrawal period. This assessment will focus on subjects with moderate to severe **hidradenitis suppurativa** who were HiSCR responders at Week 52 in the core studies. HiSCR response is defined as at least a 50% decrease in the number of abscesses and inflammatory nodules (AN) relative to the Baseline visit in the core study, with no increase in the number of abscesses and draining fistulae. Loss of response is defined as at least a 50% or greater increase in AN count (abscess and/or nodules) at a regular or unscheduled visit.

Secondary endpoints will include the assessment of adverse events, laboratory values, and vital signs. These parameters will be collected and analyzed throughout the study to ensure comprehensive evaluation of the treatment's efficacy and safety profile. The trial is designed to demonstrate the long-term efficacy, safety, and tolerability of subcutaneous secukinumab in the specified patient population. The study will follow a multicenter, double-blind, randomized withdrawal extension design to achieve these objectives.