Efficacy, Safety, and Pharmacokinetics of Apremilast in Pediatric Patients with Active Juvenile Psoriatic Arthritis: A Phase 3, Multicenter, Double-Blind, Randomized Study

The primary objective of this study is to estimate the **efficacy** of apremilast compared with placebo in the treatment of **Juvenile Psoriatic Arthritis** (JPsA) in pediatric subjects aged 5 to less than 18 years. This is clinically relevant as it aims to determine the potential of apremilast as a therapeutic option for managing JPsA, a condition that can significantly impact the quality of life and physical function in affected children.

Secondary objectives include:

• Estimating the effect of apremilast compared to placebo on pain, ACR Pedi 20/50/70/90 response, respective core components, and juvenile arthritis disease activity in pediatric subjects with JPsA.
• Assessing the impact on health-related quality of life (HRQoL) and the efficacy of apremilast compared to placebo for overall JPsA-related disease activity.
• Evaluating the effect on psoriatic arthritis flares and psoriatic skin disease.
• Determining the safety and tolerability of apremilast compared with placebo.
• Characterizing the pharmacokinetics of apremilast in pediatric subjects with JPsA.
• Evaluating the taste and acceptability of apremilast tablet and suspension.

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 a confirmed diagnosis of juvenile psoriatic arthritis according to the International League of Associations for Rheumatology (ILAR) Edmonton Revision classification criteria, with the condition persisting for at least six months. The trial includes individuals with active disease, defined by the presence of at least three active joints, and those who have shown an inadequate response or intolerance to at least one disease-modifying antirheumatic drug (DMARD). The trial population is characterized by a vulnerable group, given the pediatric nature of the participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase 3**, multicenter, double-blind, randomized, placebo-controlled, parallel group study designed to evaluate the efficacy, safety, and pharmacokinetics of **Apremilast** in pediatric subjects aged 5 to less than 18 years with active **juvenile psoriatic arthritis**. The primary objective is to estimate the efficacy of Apremilast compared to placebo. The trial is expected to run from February 22, 2022, to December 29, 2028, with a maximum treatment period of 52 weeks for each participant.

Participants will be randomly assigned to receive either Apremilast or a placebo, both administered orally. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and disease activity; baseline assessments at week 0; and subsequent follow-up visits at regular intervals to monitor efficacy and safety outcomes. The primary endpoint is the number of participants achieving ACR Pedi 30 from baseline to week 16. Secondary endpoints include changes in pain assessment, CHAQ, JADAS, and PASI-75 response, among others.

The expected length of participant involvement is up to 52 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial will adhere to rigorous standards to ensure the integrity and reliability of the data collected, with all procedures conducted in accordance with ethical guidelines and regulatory requirements.

The clinical trial involves the administration of **Apremilast**, a chemical compound, as the experimental medication. Apremilast is provided in three pharmaceutical forms: film-coated tablets, film-coated tablets, and oral solution. The film-coated tablets are available in dosages of 10 mg, 20 mg, and 30 mg, while the oral solution is provided at a concentration of 5 mg/mL. The maximum daily dose of Apremilast is 60 mg, with a total maximum dose of 21,840 mg over a treatment period of up to 52 weeks. The route of administration for all forms is oral. The medication is identified by the sponsor product code AMG 407 and is manufactured by Amgen Inc. Participant compliance with the dosing schedule will be monitored throughout the study.

The study also includes a **placebo** treatment, which is designed to match the experimental medication in appearance and administration form but does not contain the active substance, Apremilast. The placebo is supplied as 10 mg, 20 mg, and 30 mg tablets, as well as a 5 mg/mL oral solution. The placebo serves as a comparator to evaluate the efficacy and safety of Apremilast in the treatment of Juvenile Psoriatic Arthritis in pediatric subjects aged 5 to less than 18 years. The administration of the placebo follows the same oral route and dosing schedule as the active medication to ensure blinding and maintain the integrity of the study design.

The efficacy of **Apremilast** in the treatment of Juvenile Psoriatic Arthritis will be assessed through a Phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel group study. The primary endpoint for evaluating efficacy is the number of participants achieving ACR Pedi 30 from baseline (week 0) to week 16. Secondary endpoints include changes in the subject's assessment of pain, the number of participants achieving ACR Pedi 20/50/70/90, changes in the Childhood Health Assessment Questionnaire (CHAQ), changes in the Juvenile Arthritis Disease Activity Score (JADAS), PASI-75 response at week 16 for subjects with a baseline psoriasis BSA of 3% or more, and the number of participants who experience PsA flares.

Efficacy parameters will be measured and collected at specified timepoints, with the primary endpoint assessed at week 16. The study will utilize validated scales and patient-reported outcomes to ensure accurate and reliable data collection. The analysis of these efficacy parameters will be conducted in accordance with the study protocol, ensuring a rigorous evaluation of the treatment's impact on the disease.