A Seamless Phase 2a/2b, Randomized, Double-Blind, Placebo- and Active-Controlled, Multiple-Arm, Multiple-Stage, Adaptive Study Evaluating the Efficacy and Safety of LAD191 in Adults With Moderate-to-Severe Hidradenitis Suppurativa

This adaptive, seamless Phase 2a/2b clinical trial evaluates LAD191, a novel investigational agent, in adults with moderate-to-severe hidradenitis suppurativa. The primary objectives are to assess the efficacy of multiple dosing regimens of LAD191 compared to placebo in patients with moderate-to-severe hidradenitis suppurativa, and to assess the safety and tolerability of multiple dosing regimens of LAD191 in this patient population. The study employs a randomized, double-blind, placebo- and active-controlled design with multiple arms and stages. Adalimumab serves as the active comparator. The trial's adaptive design allows for evaluation of various dosing strategies to identify optimal therapeutic regimens. Immunogenicity assessment is included as part of the trial scope. This investigation addresses a significant unmet clinical need in the management of hidradenitis suppurativa, a chronic inflammatory skin condition characterized by painful nodules, abscesses, and scarring in intertriginous areas.

This clinical trial enrolled a total of **25 participants** diagnosed with **moderate-to-severe hidradenitis suppurativa**. The study population consisted of both male and female adults aged **18 to 65 years**, with a **body mass index** not exceeding **40 kg/m²**. Participants were required to have a documented history of hidradenitis suppurativa signs and symptoms for at least **6 months** prior to enrollment. The trial population was selected based on the presence of at least **5 inflammatory lesions** (abscesses and inflammatory nodules) at screening and baseline visits, with lesions present in at least **2 distinct anatomic areas**, one of which had to be classified as **Hurley Stage II** or **Hurley Stage III**. Eligible participants had a history of inadequate response, intolerance, or contraindication to **systemic antibiotics** for hidradenitis suppurativa treatment. Regarding lifestyle considerations, participants were required to use over-the-counter **topical antiseptics** on affected lesions regularly for at least 2 weeks before baseline and to continue this practice throughout the study, preferably daily but at minimum 3 days per week. Women of child-bearing potential and male participants were required to comply with pregnancy avoidance measures during the trial period.

This is a seamless phase 2a/2b, randomized, double-blind, placebo- and active-controlled, multiple-arm, multiple-stage, adaptive clinical trial designed to evaluate the efficacy and safety of LAD191 in adults with moderate-to-severe hidradenitis suppurativa. The study employs an adaptive design with multiple treatment arms, allowing for flexible evaluation of various dosing regimens of LAD191 compared to placebo and active comparators, specifically adalimumab and sodium chloride. All investigational products are administered via subcutaneous route as solution for injection. The trial aims to assess the efficacy of multiple dosing regimens of LAD191 compared to placebo in patients with moderate-to-severe hidradenitis suppurativa, as well as to evaluate the safety and tolerability of these regimens.

The study is designed for adult participants aged 18 to 65 years with a body mass index of 40 kg/m² or less who have a diagnosis of moderate-to-severe hidradenitis suppurativa defined as a total of 5 or more inflammatory lesions, including abscesses and inflammatory nodules, present at both screening and baseline visits. Participants must have experienced signs and symptoms of hidradenitis suppurativa for at least 6 months and must have lesions present in at least 2 distinct anatomic areas, with one area classified as at least Hurley Stage II or Hurley Stage III. Eligible participants must have a documented history of inadequate response, intolerance, or contraindication to systemic antibiotic therapy for hidradenitis suppurativa treatment. Regular use of over-the-counter topical antiseptics on affected lesions for at least 2 weeks prior to baseline is required, with continued use throughout the study period at a minimum frequency of 3 days per week. Women of child-bearing potential and male participants must agree to specific contraceptive requirements to avoid pregnancy and exposure to the investigational product during the study.

The primary efficacy endpoint is the proportion of participants achieving HiSCR 50 response. Safety endpoints include the frequency and severity of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and adverse events of special interest. Additional safety assessments encompass local tolerance at injection sites, vital signs, electrocardiograms, and clinical laboratory parameters. The trial is estimated to commence recruitment in October 2025 with an anticipated completion date of July 2027. The total duration of the study spans approximately 21 months from the start of recruitment to the estimated end date. Participant involvement duration and specific visit schedules have not been detailed in the available protocol information. Conditions that may lead to early termination from the study include the occurrence of adverse events necessitating discontinuation, as monitored throughout the trial period.

The experimental medication LAD191 (also known as ISB 880) is administered as a solution for injection via subcutaneous use. LAD191 is a protein-based active substance manufactured by ALMIRALL, S.A. Multiple dosing regimens of LAD191 are evaluated in this study to assess efficacy and safety in patients with moderate-to-severe hidradenitis suppurativa. The maximum treatment period is specified as one day, indicating a study design that involves repeated administration cycles.

Adalimumab serves as an active comparator in this trial. Adalimumab is administered as a solution for injection via subcutaneous use. This protein-based medication is used as a reference treatment to compare the efficacy and safety profile of the experimental medication LAD191. The maximum treatment period for adalimumab is one day, consistent with the study's dosing schedule design.

LAD191 placebo is included as a placebo control arm in this randomized, double-blind study. The placebo is designed to match the experimental medication to maintain blinding throughout the trial. The use of placebo allows for the assessment of the true therapeutic effect of LAD191 by providing a baseline comparison for efficacy and safety outcomes.

Sodium chloride solution for injection is utilized as a comparator treatment via subcutaneous use. This chemical substance serves as an additional control in the study design. Sodium chloride is administered according to the same route as the experimental medication, with a maximum treatment period of one day. The inclusion of sodium chloride provides an additional reference point for evaluating the experimental medication's effects.

Efficacy will be assessed using the proportion of participants achieving **HiSCR 50** as the primary endpoint. HiSCR 50 is defined as at least a 50% reduction in the total count of inflammatory lesions (abscesses and inflammatory nodules) in participants with moderate-to-severe **hidradenitis suppurativa**. The evaluation focuses on participants presenting with a total of at least 5 inflammatory lesions at baseline, with disease manifestations in at least 2 distinct anatomic areas, one of which must be classified as Hurley Stage II or Hurley Stage III. The study will compare multiple dosing regimens of LAD191 against placebo to determine the therapeutic benefit of the investigational product in this patient population.