Efficacy, Safety, and Pharmacokinetics of Subcutaneous Risankizumab Versus Adalimumab in Pediatric Patients with Active Juvenile Psoriatic Arthritis

The primary objective of this study is to evaluate the **efficacy**, safety, tolerability, and pharmacokinetics (PK) of **risankizumab** in comparison to an adalimumab reference arm in pediatric subjects aged 5 to less than 18 years with active juvenile psoriatic arthritis (jPsA). These subjects have shown an inadequate response to, or are intolerant of, methotrexate (MTX) or other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). This evaluation is clinically relevant as it aims to provide insights into the potential benefits and risks of risankizumab as a treatment option for this patient population, potentially offering an alternative for those who do not respond well to existing therapies.

The secondary efficacy objectives include assessing the proportion of subjects who achieve the dichotomous secondary endpoints and the mean of continuous endpoints based on the intent-to-treat (ITT) population. These assessments will help further understand the treatment's impact on various clinical outcomes, contributing to a comprehensive evaluation of its therapeutic potential.

The clinical trial involves a total of **16 participants** diagnosed with **Juvenile Psoriatic Arthritis**. The study population comprises both male and female subjects aged between 5 to less than 18 years. Participants were selected based on their active disease status, specifically having active arthritis in three or more joints, and a documented inadequate response or intolerance to methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The trial does not include a vulnerable population. Participants' general health status is characterized by their active disease condition, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection criteria ensure that all participants have a confirmed diagnosis of juvenile psoriatic arthritis according to the International League of Associations for Rheumatology (ILAR) criteria for at least six months prior to screening.

The clinical trial is designed to evaluate the **efficacy**, safety, tolerability, and pharmacokinetics of **risankizumab** in pediatric subjects with active **juvenile psoriatic arthritis**. This is an open-label, randomized, assessor-blinded study with a reference arm using **adalimumab**. The trial will involve children and adolescents aged 5 to less than 18 years who have shown an inadequate response to, or intolerance of, methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The study is expected to commence recruitment in April 2024 and conclude by October 2028, with a maximum treatment period of 124 weeks for each participant.

Participants will be randomly assigned to receive either risankizumab or adalimumab, both administered via subcutaneous injection. The trial will include several key visits: an initial screening visit to confirm eligibility based on the International League of Associations for Rheumatology (ILAR) criteria, followed by a baseline visit to assess active disease in at least three joints. Subsequent follow-up visits will occur at regular intervals to monitor the primary endpoint, which is the achievement of a JIA-ACR 30 response at Week 24. Secondary endpoints include achieving JIA-ACR 50/70/90 responses, changes in JADAS-10 and JADAS-27 scores, and improvements in Psoriasis Area and Severity Index (PASI) scores for subjects with psoriasis.

The expected duration of participant involvement is up to 124 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The study aims to provide comprehensive data on the comparative effectiveness of risankizumab and adalimumab in managing juvenile psoriatic arthritis, contributing valuable insights into treatment options for this condition.

The clinical trial involves the administration of **Risankizumab**, a solution for injection in a pre-filled syringe, developed by AbbVie Deutschland GmbH & Co. KG. This experimental medication is administered subcutaneously. The dosage regimen for Risankizumab is not specified in terms of daily maximum dose, but the treatment period extends up to 124 weeks. The active substance, Risankizumab, is a protein of non-specific origin, and the formulation is not specifically designed for pediatric use.

Another experimental treatment in the study is **ABBV-066**, which is also a solution for injection in a pre-filled syringe containing Risankizumab. This medication is administered subcutaneously with a maximum daily dose of 150 mg and a total maximum dose of 1800 mg over the treatment period of 124 weeks. Like Risankizumab, ABBV-066 is not a pediatric formulation and is produced by AbbVie Deutschland GmbH & Co. KG.

The comparator treatment in the trial is **Humira**, which is available in two formulations: a 20 mg and a 40 mg solution for injection in pre-filled syringes. Both formulations contain the active substance **Adalimumab**, a protein of non-specific origin, and are administered subcutaneously. The 20 mg formulation has a maximum daily dose of 20 mg and a total maximum dose of 2480 mg over 124 weeks, while the 40 mg formulation has a maximum daily dose of 40 mg and a total maximum dose of 4960 mg over the same period. Humira is not specifically formulated for pediatric use and is also produced by AbbVie Deutschland GmbH & Co. KG.

The clinical trial aims to assess the efficacy of **risankizumab** in comparison to an adalimumab reference arm in children with active juvenile psoriatic arthritis (jPsA). Efficacy will be primarily evaluated by the achievement of the JIA-ACR 30 response at Week 24. Secondary endpoints include the achievement of JIA-ACR 50/70/90 responses, percent change from Baseline in individual components of JIA-CRV, and changes from Baseline in JADAS-10 and JADAS-27, all measured at Week 24. Additional secondary endpoints involve the achievement of Minimal Disease Activity (MDA) and inactive disease, defined by specific JADAS-10 scores, as well as changes in cJADAS-10, cJADAS-27, and Pain-VAS at Week 24.

For subjects with psoriasis (PsO) affecting at least 3% of the body surface area at Baseline, efficacy will also be assessed by the achievement of PASI 75/90 and the sPGA of PsO of 'clear' or 'almost clear' (0/1) at Week 24. Changes from Baseline in the Children's Dermatology Life Quality Index (CDLQI) will also be evaluated at Week 24. These efficacy parameters will be collected and analyzed at the specified timepoints to determine the therapeutic impact of **risankizumab** in the target population.