A Multicenter, Randomized, Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Deucravacitinib (BMS-986165) in Pediatric Subjects with Moderate to Severe Plaque Psoriasis

The primary objective of this multicenter, randomized, double-blind, placebo-controlled Phase 3 study is to evaluate the **pharmacokinetics** of deucravacitinib at steady-state in pediatric subjects with moderate to severe plaque psoriasis. This evaluation is conducted in two cohorts: Cohort 1 includes subjects aged 12 to less than 18 years, and Cohort 2 includes subjects aged 4 to less than 12 years. Understanding the pharmacokinetics in these age groups is crucial for determining appropriate dosing regimens and ensuring therapeutic efficacy and safety in pediatric populations.

Additionally, the study aims to assess the efficacy of the standard dose of deucravacitinib compared to placebo in the same cohorts. This is clinically relevant as it provides insights into the potential benefits of deucravacitinib in managing moderate to severe plaque psoriasis in children, a population that may have different therapeutic needs compared to adults. Furthermore, the study includes a long-term extension (LTE) period to characterize the safety and tolerability of deucravacitinib in these pediatric subjects, which is essential for understanding the long-term implications of treatment in this demographic.

The clinical trial involves a total of **71 participants** diagnosed with **moderate to severe plaque psoriasis**. The study population is divided into two cohorts based on age: Cohort 1 includes individuals aged 12 to less than 18 years, and Cohort 2 comprises those aged 4 to less than 12 years. Both male and female subjects are included in the trial. Participants were selected based on their stable condition, defined by no significant flares or morphologic changes for six months, and a Psoriasis Area and Severity Index (PASI) of 12 or greater, a static Physician's Global Assessment (sPGA) of 3 or greater, and Body Surface Area (BSA) involvement of 10% or more. The trial population includes candidates for phototherapy or systemic therapy. The study also considers vulnerable populations, ensuring that all participants have provided informed consent or assent according to local laws and regulations. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** Phase 3 study to evaluate the pharmacokinetics, efficacy, and safety of **deucravacitinib** in pediatric subjects with moderate to severe plaque psoriasis. The trial is structured into two main parts: Part A focuses on pharmacokinetics, while Part B assesses efficacy. The trial also includes a long-term extension (LTE) period to evaluate safety and tolerability. The study is expected to last until September 2031, with recruitment having commenced in February 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease stability, and severity. Eligible participants will be randomized into treatment groups. The trial includes multiple follow-up visits to monitor pharmacokinetic parameters, efficacy outcomes, and safety assessments. The end-of-study visit will conclude the participant's involvement, unless they opt to continue into the LTE period, which requires completion of the 52-week treatment period in Part A or B.

The expected length of participant involvement is up to 52 weeks, with the possibility of extension into the LTE period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The primary endpoints include pharmacokinetic measures such as geometric mean observed average concentration at steady state, and efficacy measures like the proportion of subjects achieving at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75). Safety endpoints include monitoring adverse events and growth parameters.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound, in various pharmaceutical forms and dosages. The primary experimental medication is deucravacitinib, provided as a **film-coated tablet**. The active substance, deucravacitinib, is chemically synthesized and is administered orally. The maximum daily dose is 6 mg, with a total maximum dose of 2184 mg over a treatment period of up to 52 weeks. The film-coated tablet form is produced by Bristol-Myers Squibb International Corporation and is identified by the sponsor product code BMS-986165. The trial also includes a formulation of deucravacitinib as film-coated tablets and gastro-resistant granules in sachets, which are also administered orally.

In addition to the film-coated tablet, the trial includes deucravacitinib in sachet form, available in 1 mg, 2 mg, and 3 mg dosages. These sachets are not specified with a pharmaceutical form and are also administered orally. The sachet formulations are not pediatric-specific and are used in conjunction with the film-coated tablets to evaluate the pharmacokinetics, efficacy, and safety of deucravacitinib in pediatric subjects with moderate to severe plaque psoriasis.

The study design includes a placebo-controlled group to assess the efficacy of deucravacitinib against a non-active comparator. The placebo is administered in a manner consistent with the active treatment to maintain the double-blind nature of the trial. Participant compliance is monitored through regular assessments and adherence checks to ensure accurate evaluation of the treatment's effects.

The efficacy of **deucravacitinib** in the clinical trial will be assessed using specific primary endpoints. In Part B of the study, the primary efficacy endpoints include the proportion of subjects achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) and the proportion of subjects with a static Physician's Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline. These endpoints are designed to evaluate the effectiveness of deucravacitinib in treating moderate to severe plaque psoriasis in pediatric subjects.

The efficacy parameters will be measured and collected at designated timepoints throughout the trial. The PASI and sPGA scores will be assessed at baseline and at subsequent visits to monitor changes in disease severity and treatment response. The analysis of these efficacy parameters will involve comparing the outcomes between the treatment group receiving deucravacitinib and the placebo group. The trial is structured to ensure that the data collected is robust and reliable, providing a comprehensive evaluation of the drug's efficacy in the target population.