Comparison of Adjustable Versus Standard Brodalumab Dosage Regimens in Patients with Moderate-to-Severe Plaque Psoriasis and Body Weight ≥120 kg

The primary objective of this study is to compare the effect on **psoriasis** symptoms of an adjustable **brodalumab** dosage regimen to standard brodalumab treatment in subjects with moderate-to-severe plaque psoriasis and a body weight of at least 120 kg. This is clinically relevant as it aims to optimize treatment efficacy and safety for a specific patient population with significant disease burden.

Secondary objectives include:

• Evaluating the safety of an adjustable brodalumab dosage regimen in the specified patient group.
• Assessing the pharmacokinetics of brodalumab in these subjects.
• Exploring the effect of brodalumab on systemic inflammation.
• Investigating the impact of brodalumab on skin and subcutaneous adipose tissue inflammation.

The clinical trial involves a total of **32 participants** diagnosed with **moderate-to-severe plaque psoriasis** and a body weight of at least 120 kg. The study population includes both male and female subjects, aged between 18 and 74 years, who are in general good health aside from their psoriasis condition. Participants were selected based on specific inclusion criteria, such as having a diagnosis of chronic plaque psoriasis for at least six months prior to randomization and meeting certain body surface area and Psoriasis Area and Severity Index thresholds. The trial does not include a vulnerable population, and there are no specific lifestyle considerations such as diet or physical activity mentioned. Key inclusion criteria also required participants to have no evidence of active or latent tuberculosis, ensuring suitability for biologic treatment initiation.

The clinical trial is designed to evaluate the efficacy of an adjustable **brodalumab** dosage regimen compared to a standard treatment in subjects with moderate-to-severe plaque psoriasis and a body weight of at least 120 kg. This is a randomized, double-blind, controlled, parallel-group, multi-center trial. The trial is expected to last for approximately 52 weeks, with participant involvement spanning the same duration. The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. The screening visit will confirm eligibility based on criteria such as age, diagnosis of chronic plaque psoriasis, and body weight. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment, with primary and secondary endpoints assessed at Weeks 40 and 52. The primary endpoint is achieving at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90 response) at Week 40. Secondary endpoints include achieving a static Physician’s Global Assessment (sPGA) score of 0 or 1 and other measures of improvement in psoriasis symptoms and quality of life. Participants may be withdrawn from the study if they do not adhere to the protocol, experience adverse effects, or choose to discontinue participation. The trial will utilize a placebo control, with the placebo being a pre-filled syringe containing the same excipients as the investigational medicinal product, without the active substance. The trial aims to provide valuable insights into the management of moderate-to-severe plaque psoriasis in a specific patient population.

The clinical trial involves the administration of **Kyntheum**, a pharmaceutical product containing the active substance **brodalumab**. Kyntheum is provided as a **solution for injection in a pre-filled syringe**, with each syringe containing 210 mg of brodalumab. The medication is administered via subcutaneous injection. The maximum daily dose is 210 mg, with a total maximum dose of 6930 mg over the treatment period. The treatment period is set for a maximum of 2 weeks. The product is manufactured by LEO Pharma A/S and is authorized for use in the European Union under the marketing authorization number EU/1/16/1155/001.

Another formulation of brodalumab used in the trial is a 70 mg solution for injection, also provided in a pre-filled syringe. This formulation is similarly administered subcutaneously. The maximum daily dose for this formulation is 280 mg, with the same total maximum dose of 6930 mg over the treatment period of 2 weeks. This product is also manufactured by LEO Pharma A/S and is identified by the sponsor product code LP0160.

The trial includes a **placebo** control, which is presented as a pre-filled syringe containing the same excipients as the investigational medicinal product (IMP) but without the active substance. The placebo is designed to match the IMP in appearance and administration method to maintain the double-blind nature of the study. The placebo is used to assess the efficacy of the active treatment by providing a baseline for comparison.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the achievement of at least a 90% reduction in the **Psoriasis Area and Severity Index (PASI)** score relative to baseline, known as PASI 90 response, at Week 40. Secondary endpoints include achieving a static Physician’s Global Assessment (sPGA) score of 0 or 1 at Week 40, PASI 90 response at Week 52, and sPGA score of 0 or 1 at Week 52. Additional secondary endpoints involve the sPGA of genitalia (sPGA-G) score of 0 or 1 at both Weeks 40 and 52, PASI 100 response at Weeks 40 and 52, and changes from baseline in PASI score and affected body surface area (BSA) at Weeks 40 and 52. The Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Weeks 40 and 52, as well as changes from baseline in DLQI total score at these timepoints, will also be evaluated.

The efficacy parameters will be measured and collected at specified timepoints, including Weeks 40 and 52, using validated scales such as PASI and sPGA. The analysis will focus on comparing the effect of an adjustable brodalumab dosage regimen to standard brodalumab treatment in subjects with moderate-to-severe plaque psoriasis and a body weight of at least 120 kg. The trial is designed as a randomized, double-blind, controlled, parallel-group, multi-centre study, ensuring robust and reliable data collection and analysis.