Efficacy and Safety Evaluation of Bimekizumab Versus Ustekinumab in Pediatric Patients with Moderate to Severe Plaque Psoriasis

The primary objective of this study is to evaluate the **efficacy** of bimekizumab administered subcutaneously compared to the active control, ustekinumab, in children and adolescents aged 6 to less than 18 years with moderate to severe plaque psoriasis. This is clinically relevant as it aims to determine the potential of bimekizumab as a therapeutic option for this age group, potentially offering an alternative treatment for managing moderate to severe plaque psoriasis, a condition that can significantly impact quality of life.

Secondary objectives include:

• Evaluating the efficacy of bimekizumab compared to ustekinumab in the same population.
• Assessing the safety profile of bimekizumab relative to ustekinumab.
• Evaluating the effect of bimekizumab on health-related quality of life compared to ustekinumab.
• Assessing the pharmacokinetics of bimekizumab when administered subcutaneously.
• Evaluating the immunogenicity of bimekizumab when administered subcutaneously.

The clinical trial involves a total of **46 participants** diagnosed with **moderate to severe plaque psoriasis**. The study population comprises children and adolescents aged 6 to less than 18 years, including both male and female subjects. Participants were selected based on specific criteria, including a diagnosis of moderate to severe plaque psoriasis for at least three months prior to the screening visit. The trial includes individuals with a body surface area affected by psoriasis of at least 10%, an Investigator's Global Assessment score of 3 or higher, and a Psoriasis Area and Severity Index score of 12 or higher, or a score of 10 with clinically relevant involvement of the face, genitals, hands, or feet. Participants are candidates for systemic psoriasis therapy and/or photochemotherapy, and they meet the weight and body mass index requirements for their age. The trial population is considered vulnerable, given the age range and health condition of the participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, parallel-group, double-blind, active-controlled study to evaluate the efficacy and safety of **bimekizumab** compared to **ustekinumab** in children and adolescents aged 6 to less than 18 years with moderate to severe plaque psoriasis. The trial will involve subcutaneous administration of the investigational medicinal products. The study is expected to last until November 2030, with recruitment starting in July 2024. The trial will include several key phases, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis duration, and severity of psoriasis. Participants must have a body surface area affected by psoriasis of at least 10%, an Investigator's Global Assessment score of 3 or higher, and a Psoriasis Area and Severity Index score of 12 or more, among other criteria.

Following the screening, eligible participants will be randomized to receive either bimekizumab or ustekinumab, with a placebo comparator also included in the study design. The primary endpoints will be assessed at Week 16, focusing on the Psoriasis Area Severity Index 90 response and the Investigator's Global Assessment 0/1 response. Secondary endpoints will include various efficacy and safety measures, such as PASI75 and PASI100 responses, treatment-emergent adverse events, and changes in quality of life indices. Study visits will be scheduled at regular intervals to monitor these outcomes, with follow-up visits extending up to Week 48 to assess long-term effects and safety.

The expected length of participant involvement is up to 152 weeks, depending on the treatment arm and individual response. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The study aims to provide comprehensive data on the comparative efficacy and safety of bimekizumab and ustekinumab in the pediatric population with moderate to severe plaque psoriasis, contributing valuable insights into treatment options for this condition.

The clinical trial involves the administration of **bimekizumab**, a **solution for injection** formulated by UCB Biopharma SRL. Bimekizumab is a protein-based therapeutic agent, specifically designed for **subcutaneous use**. The drug is supplied in a 1mL Type I glass pre-filled syringe, equipped with a staked 27G, ½ inch thin wall needle. The syringe is sealed with a fluropolymer laminated bromobutyl rubber stopper and a rigid needle shield. The maximum treatment period for bimekizumab is 152 weeks. The dosing schedule and frequency of administration are determined by the study protocol, ensuring adherence to the trial's objectives and safety parameters.

**Ustekinumab** is utilized as an active comparator in this study. It is also a **solution for injection** and is administered via the **subcutaneous route**. The maximum daily dose of ustekinumab is 90 mg, with a total treatment period of 48 weeks. The drug is delivered using a single-dose pre-filled syringe with a 27 gauge fixed ½ inch needle, which includes a passive needle guard and a needle cover containing dry natural rubber. Participant compliance with the dosing regimen is monitored throughout the trial to ensure accurate assessment of the drug's efficacy and safety.

The study also incorporates a **placebo** control, consisting of a 0.9% sodium chloride solution for injection. This placebo is designed to match the test and comparator treatments in appearance and administration method. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased results. The placebo is administered according to the same schedule as the active treatments, with compliance monitoring in place to maintain the integrity of the study data.

The efficacy of the investigational medicinal product, **bimekizumab**, will be assessed in a clinical trial involving children and adolescents aged 6 to less than 18 years with moderate to severe plaque psoriasis. The primary endpoints for evaluating efficacy include the Psoriasis Area Severity Index 90 (PASI90) response and the Investigator's Global Assessment (IGA) 0/1 response, both measured at Week 16. Secondary endpoints include PASI75 response at Week 4, PASI100 response at Week 16, PASI90 response at Week 48, IGA 0/1 response at Week 48, PASI100 response at Week 48, IGA 0 response at Week 16, and IGA 0 response at Week 48.

Additional secondary endpoints involve safety assessments such as treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs leading to discontinuation of the investigational medicinal product, and TEAEs leading to withdrawal from the study. Selected safety topics of interest, including infections, inflammatory bowel disease, and injection site reactions, will be monitored from the first dose through 20 weeks after the final dose. Changes from baseline in vital signs, physical examination findings, growth assessments, laboratory analyses, and quality of life indices will also be evaluated. Plasma concentrations of bimekizumab and anti-bimekizumab antibodies will be measured throughout the treatment periods.