Evaluation of Efficacy, Pharmacokinetics, Safety, and Immunogenicity of Subcutaneous Ustekinumab and Guselkumab in Pediatric Patients with Active Juvenile Psoriatic Arthritis

The primary objective of this study is to evaluate the **pharmacokinetics** (PK) and efficacy of subcutaneously administered ustekinumab and guselkumab in pediatric participants with active juvenile psoriatic arthritis (jPsA). Understanding the PK profile is crucial for determining the appropriate dosing regimen, ensuring optimal therapeutic outcomes, and minimizing potential adverse effects. Evaluating efficacy is essential to establish the therapeutic benefits of these treatments in managing the symptoms and progression of jPsA.

Secondary objectives include:

• Evaluating the safety of ustekinumab and guselkumab in jPsA, which is vital for assessing the risk-benefit profile of these treatments.
• Assessing the immunogenicity of ustekinumab and guselkumab, which is important for understanding the potential for immune response development that could affect treatment efficacy and safety.

The clinical trial involves a total of **28 participants** diagnosed with **juvenile psoriatic arthritis**. The study population includes both male and female subjects, aged between 5 to less than 18 years. Participants were selected based on specific inclusion criteria, which required a diagnosis of juvenile psoriatic arthritis according to the Vancouver inclusion criteria, with the exclusion of enthesitis-related arthritis. The diagnosis must have been made at least three months prior to screening. Participants are required to have active disease in at least three joints at screening and at Week 0, characterized by swelling or loss of motion with pain and/or tenderness. The trial includes individuals who have active disease despite previous treatment with non-biologic DMARDs and/or NSAIDs. The study population is considered vulnerable due to the age range and health condition. Lifestyle considerations such as diet and physical activity are not specified in the available data.

This clinical trial is a Phase 3, open-label, multicenter study designed to evaluate the **efficacy**, pharmacokinetics, safety, and immunogenicity of subcutaneously administered **ustekinumab** and **guselkumab** in pediatric participants with active juvenile psoriatic arthritis. The trial involves two cohorts, with each cohort receiving one of the study drugs. The study is not classified as low intervention and is expected to last until August 2027, with recruitment having commenced in June 2023. The trial is structured to include a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis, and disease activity. Participants must be between 5 and 18 years of age and have a confirmed diagnosis of juvenile psoriatic arthritis with active disease in at least three joints.

The trial design is open-label, meaning both the participants and the investigators are aware of the treatment being administered. The study will include regular follow-up visits to monitor the pharmacokinetics and efficacy of the treatments, with primary endpoints assessed at Week 24 and Week 28. Secondary endpoints will be evaluated at various intervals, including Weeks 4, 8, 12, 16, 24, and 52. The end-of-study visit will occur at Week 52, marking the conclusion of the participant's involvement in the trial. The expected duration of participation for each individual is approximately 52 weeks, with conditions for early termination including adverse events, lack of efficacy, or withdrawal of consent.

Throughout the trial, participants will receive either **ustekinumab** or **guselkumab** via subcutaneous injection, with dosing intervals tailored to each drug's pharmacokinetic profile. The study aims to gather comprehensive data on the steady-state trough concentrations and population pharmacokinetic model-predicted area under the curve (AUC) for both drugs. Safety assessments will include monitoring for adverse events and serious adverse events, while immunogenicity will be evaluated by measuring the incidence of antibodies to the study drugs. The trial's findings will contribute to understanding the potential use of these treatments in managing juvenile psoriatic arthritis.

The clinical trial involves the administration of **Guselkumab**, a solution for injection in a pre-filled syringe, with a concentration of 100 mg/mL. This experimental medication is administered subcutaneously. The maximum daily dose is 100 mg, and the treatment period extends up to 52 weeks. The administration device used is the UltraSafe Plus™ Passive Needle Guard, which facilitates self-injection and ensures passive activation of the needle guard post-delivery. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

Another formulation of **Guselkumab** is also utilized in the study, presented as a solution for injection in a pre-filled syringe. This formulation is dosed at 1.3 mg/kg, with the same subcutaneous route of administration and a maximum treatment period of 52 weeks. The VarioJect variable dose injector is employed for this formulation, allowing for the delivery of a single variable dose. Compliance monitoring is similarly conducted to ensure proper administration and adherence to the protocol.

The trial also includes the administration of **Ustekinumab**, marketed as STELARA, available in two different dosages: 90 mg and 45 mg solutions for injection in pre-filled syringes. Both formulations are administered subcutaneously, with a maximum daily dose of 90 mg and a treatment duration of up to 52 weeks. The UltraSafe Passive Delivery System is used with the 90 mg formulation, providing a needle guard system that confirms to ISO standards. Compliance is monitored to ensure participants adhere to the prescribed dosing regimen.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of **Ustekinumab** and **Guselkumab** steady-state trough concentrations and population pharmacokinetic (PK) model-predicted area under the curve at steady state (AUCss) over specified dosing intervals at Week 28, stratified by baseline age groups. Additionally, the American College of Rheumatology (ACR) Pediatric 30 response at Week 24 will be measured for both **Ustekinumab** and **Guselkumab**.

Secondary endpoints will further assess efficacy through various measures. These include the ACR Pedi 30, 50, and 70 responses at multiple timepoints (Weeks 4, 8, 12, 16, 24, and 52) for both drugs. The time to response, defined as the time to achieving ACR Pedi 30 from baseline through Week 24, will also be evaluated. Changes from baseline in the clinical Juvenile Arthritis Disease Activity Score (cJADAS) 10, JADAS 10, 27, and 71 at specified weeks, as well as changes in the Psoriasis Area and Severity Index (PASI) score at Week 24 for participants with significant psoriatic involvement, will be analyzed.

Data collection will occur at designated intervals throughout the trial, with efficacy assessments conducted using validated scales and laboratory tests. The trial will employ a multicenter, open-label design to evaluate these parameters in pediatric participants with active juvenile psoriatic arthritis. The study is structured to ensure comprehensive data collection and analysis, facilitating a robust evaluation of the efficacy of **Ustekinumab** and **Guselkumab** in this patient population.