Efficacy, Safety, and Pharmacokinetics of Deucravacitinib in Pediatric Patients with Active Juvenile Psoriatic Arthritis: A Phase 3 Randomized Withdrawal Study

The primary objective of this study is to evaluate the efficacy of **deucravacitinib** compared to placebo in pediatric patients aged 5 to less than 18 years with active Juvenile Psoriatic Arthritis (JPsA). This is clinically relevant as it aims to determine the potential of deucravacitinib to improve disease outcomes in this specific patient population, potentially offering a new therapeutic option for managing JPsA.

Secondary objectives include:

• Understanding the pharmacokinetics (PK) of deucravacitinib in children and adolescents, which is crucial for optimizing dosing regimens.
• Evaluating the efficacy of deucravacitinib compared to placebo using alternative response measures.
• Assessing the palatability and ease of administration of the medication, as these factors can influence adherence in pediatric patients.
• Investigating the exposure-response (E-R) relationship to understand how the drug's concentration correlates with its effects.
• Ensuring the safety and tolerability of deucravacitinib in the pediatric population, which is essential for its potential approval and use in clinical practice.

The clinical trial involves a total of **35 participants** diagnosed with **Juvenile Psoriatic Arthritis (JPsA)**. The study population comprises both male and female subjects, aged between 5 and 18 years. Participants were selected based on their diagnosis of JPsA, which includes arthritis and skin conditions such as **Psoriasis (PsO)**, or arthritis with symptoms like dactylitis, nail changes, or a family history of PsO. The trial includes individuals who have at least three affected joints and have previously tried at least one medication for JPsA without satisfactory results. The study population is considered vulnerable due to the age range and health condition. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, multicenter, double-blind, placebo-controlled, randomized withdrawal study designed to evaluate the efficacy, safety, and pharmacokinetics of **deucravacitinib** in pediatric participants aged 5 to less than 18 years with active **Juvenile Psoriatic Arthritis (JPsA)**. The trial aims to determine if deucravacitinib is more effective than a placebo in managing the condition. The study is expected to commence recruitment on February 3, 2025, and conclude by March 4, 2031. Participants will be randomly assigned to receive either deucravacitinib or a placebo, with the primary endpoint being the time to the first disease flare-up between weeks 16 to 42. Secondary endpoints include evaluating the pharmacokinetics of deucravacitinib, assessing disease activity, and monitoring side effects.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of JPsA, involvement of at least three joints, and previous treatment attempts. Following randomization, participants will attend regular follow-up visits to monitor their response to the treatment, assess any adverse effects, and evaluate the pharmacokinetics of the drug. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted to evaluate the overall efficacy and safety of the intervention.

The expected duration of participant involvement in the trial is up to 94 weeks, depending on the treatment group assignment. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, non-compliance with study procedures, or withdrawal of consent by the participant or their legal guardian. The trial is structured to ensure rigorous monitoring and evaluation of the investigational product, with the aim of providing comprehensive data on its potential benefits and risks in the target population.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound developed by Bristol-Myers Squibb International Corporation. Deucravacitinib is provided in the form of a **film-coated tablet**. The active substance, deucravacitinib, is chemically synthesized and is also known by its synonyms BMS986165 and 6-((cyclopropylcarbonyl)amino]-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-((2H3)methyl)pyridazine-3-carboxamide. The medication is administered orally, with a maximum daily dose of 6 mg. The treatment duration varies, with a maximum total dose of 408 mg over 68 days, 564 mg over 94 days, or 312 mg over 52 days, depending on the specific protocol followed within the trial.

In addition to the experimental medication, a **placebo** is utilized in the study. The placebo is presented as 2 mg film-coated tablets in sachets, intended for oral use. The placebo serves as a control to evaluate the efficacy and safety of deucravacitinib in the treatment of active Juvenile Psoriatic Arthritis in children and adolescents aged 5 to less than 18 years. The use of a placebo allows for a double-blind, placebo-controlled, randomized withdrawal trial design, ensuring the reliability and validity of the study outcomes.

The efficacy of deucravacitinib in treating **Juvenile Psoriatic Arthritis** (JPsA) will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the time to the first disease flare-up occurring between weeks 16 to 42 in participants who continue the medication compared to those who discontinue it. This will provide a direct measure of the drug's ability to maintain disease control over time.

Secondary endpoints will include several measures to provide a comprehensive evaluation of the drug's efficacy. These include assessing the amount of deucravacitinib in the body at week 16, the number of participants experiencing a flare-up, and those achieving various levels of improvement at weeks 16 and 42. Additionally, the trial will evaluate the improvement in disease activity from the start of the trial, the number of participants with low or no disease activity at specified time points, and those maintaining no disease activity for at least six consecutive months. The trial will also assess the percentage of participants achieving a 75% improvement in skin symptoms by week 42.

Further assessments will include the ease of swallowing and palatability of the medication at week 16, the relationship between the drug concentration in the body and clinical outcomes, and the monitoring of side effects, including the development of uveitis. These endpoints will be measured using validated scales and laboratory tests at specified time points throughout the trial, ensuring a robust and comprehensive evaluation of deucravacitinib's efficacy in the target population.