Phase 3 Multicenter Randomized Double-Blind Placebo-Controlled Trial Evaluating Lutikizumab Efficacy and Safety in Moderate to Severe Hidradenitis Suppurativa

The primary objective of this study is to assess the **efficacy** of lutikizumab versus placebo in the treatment of the signs and symptoms of moderate to severe **Hidradenitis Suppurativa** (HS) in subjects aged 16 years and older. This is clinically relevant as HS is a chronic inflammatory skin condition that significantly impacts patients' quality of life, and effective treatments are needed to manage its symptoms.

Secondary objectives include: - Evaluating the efficacy and safety of continuing lutikizumab dosing in Period 1 or switching to a lower dose in subjects who received lutikizumab in Period 1. - Assessing the benefit of switching to lutikizumab in subjects who received placebo in Period 1.

The clinical trial involves a total of **850 participants** diagnosed with **Hidradenitis Suppurativa**. The study population includes both male and female subjects aged 16 years and older, with the age range extending to include young adults and middle-aged individuals. Participants were selected based on their diagnosis of moderate to severe Hidradenitis Suppurativa for at least six months prior to the baseline, as determined by medical history and clinical evaluation. The trial does not include a vulnerable population. Participants are required to have a total abscess and nodule count of five or more at baseline, with lesions present in at least two distinct anatomical areas. Additionally, at least one area of involvement must be characterized as Hurley Stage II or higher. Subjects must have previously shown an inadequate response or intolerance to a 12-week trial of oral antibiotics for the treatment of Hidradenitis Suppurativa. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided further information regarding the general health status of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **lutikizumab** in adult and adolescent subjects with moderate to severe **hidradenitis suppurativa**. The trial will involve participants aged 16 years and older, with a diagnosis of moderate to severe hidradenitis suppurativa for at least six months prior to the baseline. The study will span an estimated duration from November 2024 to October 2027, with a maximum treatment period of 51 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease severity, and previous treatment response. Following the screening, eligible participants will be randomized to receive either lutikizumab or a placebo via subcutaneous injection. The primary endpoint is the achievement of HiSCR 75 at Week 16, defined as at least a 75% reduction from baseline in the total AN count, with no increase in abscess or draining fistula counts. Secondary endpoints include various measures of symptom improvement and quality of life assessments at Weeks 8 and 16.

Participants will attend follow-up visits at regular intervals to monitor treatment efficacy and safety, with assessments including the Patient's Global Assessment of HS-related skin pain and changes in the Dermatology Life Quality Index (DLQI). The end-of-study visit will occur at the conclusion of the treatment period, where final evaluations will be conducted. Participant involvement is expected to last up to 51 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures.

The clinical trial involves the administration of **Lutikizumab**, a biotechnological product, in the form of a **solution for injection**. Lutikizumab is administered via **subcutaneous injection**. The active substance in Lutikizumab is a protein of other origin, specifically designed for the treatment of moderate to severe **Hidradenitis Suppurativa**. The pharmaceutical form is a solution for injection, and the product is identified by the sponsor product code ABT-981. The maximum treatment period for Lutikizumab is 51 weeks, with the dosage and administration schedule determined by the study protocol. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen.

The study also includes a **placebo** group, where participants receive a placebo of Lutikizumab. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring the study remains double-blind. The placebo is administered via subcutaneous injection, similar to the active treatment, to maintain consistency in the administration process. The placebo serves as a comparator to evaluate the efficacy and safety of Lutikizumab in the treatment of moderate to severe Hidradenitis Suppurativa. Compliance with the placebo administration is similarly monitored to maintain the integrity of the trial results.

The efficacy of **Lutikizumab** in the treatment of moderate to severe Hidradenitis Suppurativa (HS) will be assessed through a series of predefined endpoints. The primary endpoint is the achievement of HiSCR 75 at Week 16, which is defined as at least a 75% reduction from baseline in the total AN count, with no increase in abscess count and no increase in draining fistula count relative to baseline.

Secondary endpoints include the achievement of NRS30 at Week 8, which requires at least a 30% reduction and at least a 2-unit reduction from baseline in the Patient's Global Assessment of HS-related skin pain NRS among subjects with NRS ≥ 3 at baseline. Additional secondary endpoints at Week 16 include changes from baseline in the Dermatology Life Quality Index (DLQI), Hidradenitis Suppurativa Impact Assessment (HSIA), Hidradenitis Suppurativa Severity Assessment (HSSA) Worst Drainage Score, and the number of draining fistulas. The achievement of HiSCR 90, defined as at least a 90% reduction in the total AN count with no increase in abscess count and no increase in draining fistula count relative to baseline, will also be evaluated. Furthermore, changes from baseline in the Patient's Global Assessment of HS-related Skin Pain (NRS) at Week 8, HS-related odor based on HSSA Question 8, and the occurrence of HS flare during the first 16 weeks will be assessed.