Comparative Efficacy of Risankizumab Versus Deucravacitinib in Adult Patients with Moderate Plaque Psoriasis Eligible for Systemic Therapy

The primary objective of this study is to evaluate the **efficacy** of **risankizumab** compared to **deucravacitinib** in adult subjects with moderate **plaque psoriasis** who are candidates for systemic therapy. In Period A, the aim is to demonstrate the superiority of risankizumab in achieving PASI 90, defined as a ≥ 90% reduction from baseline in the Psoriasis Area and Severity Index, and achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-grade improvement from baseline after 16 weeks of treatment. In Period B, the objective is to demonstrate the superiority of switching to risankizumab over continuing deucravacitinib in achieving PASI 90 at Week 52 among subjects who fail to achieve PASI 90 at 16 weeks of deucravacitinib treatment. This is clinically relevant as achieving PASI 90 and sPGA 0 or 1 are significant indicators of treatment success in managing plaque psoriasis.

Secondary objectives include: - Demonstrating superior efficacy of risankizumab compared to deucravacitinib with respect to ranked secondary endpoints in Period A. - Demonstrating higher efficacy of treatment with deucravacitinib/risankizumab compared to deucravacitinib/deucravacitinib among DEU-PASI90-NRs, with respect to key secondary endpoints in a ranked order in Period B.

The clinical trial involves a total of **224 participants** diagnosed with **plaque psoriasis**. The study population comprises both male and female adults aged 18 years and above, who are candidates for systemic therapy. Participants have a diagnosis of moderate chronic plaque psoriasis, with or without psoriatic arthritis, for at least six months prior to the baseline. They have not previously been treated with biologics. At screening and baseline, participants are defined by a Body Surface Area (BSA) of 10% to 15%, a Psoriasis Area and Severity Index (PASI) of 12 or greater, and a static Physician's Global Assessment (sPGA) score of 3 on a 5-point scale. The trial includes individuals from a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed. Participants were selected based on these criteria to ensure a consistent and relevant study group for evaluating the efficacy of risankizumab compared to deucravacitinib.

The clinical trial is a Phase IV, multicenter, randomized, open-label, efficacy assessor-blinded study designed to evaluate the efficacy of **risankizumab** compared to **deucravacitinib** in adult subjects with moderate **plaque psoriasis** who are candidates for systemic therapy. The trial aims to demonstrate the superiority of risankizumab over deucravacitinib in achieving significant clinical improvements, specifically a ≥90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-grade improvement from baseline after 16 weeks of treatment. The study is structured into two periods: Period A focuses on the initial 16 weeks, while Period B extends to 52 weeks, particularly for subjects who do not achieve PASI 90 with deucravacitinib and are switched to risankizumab.

The trial will involve a sequence of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis of moderate chronic plaque psoriasis, and specific baseline disease severity measures. Participants will be randomized to receive either deucravacitinib orally or risankizumab via subcutaneous injection. Follow-up visits will occur at regular intervals to monitor efficacy and safety, with assessments including PASI and sPGA scores. The end-of-study visit will conclude the trial, evaluating the long-term outcomes and any adverse events.

The expected duration of participant involvement is up to 52 weeks, with the trial estimated to end by March 31, 2026. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to adhere to the study protocol. The trial's design ensures rigorous assessment of the primary and secondary endpoints, providing valuable insights into the comparative effectiveness of the two treatments for moderate plaque psoriasis.

The clinical trial involves the administration of **DEUCRAVACITINIB**, an experimental medication formulated as a film-coated tablet. The active substance, deucravacitinib, is of chemical origin. The medication is administered orally with a maximum daily dose of 6 mg, and the total dose over the treatment period can reach up to 2190 mg. The treatment duration is set for a maximum of 52 weeks. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, the study includes a comparator treatment, **ABBV-066**, which contains the active substance **RISANKIZUMAB**. This medication is provided as a solution for injection in a pre-filled syringe. Risankizumab is a protein-based substance, specifically categorized as "Protein - Other." The administration route is subcutaneous injection, with a maximum daily dose of 150 mg/ml and a total dose limit of 750 mg/ml over the 52-week treatment period. The comparator treatment is utilized to evaluate the efficacy of the experimental medication against a standard treatment option. Compliance with the administration schedule will be closely monitored to ensure accurate assessment of treatment outcomes.

The clinical trial aims to assess the efficacy of **risankizumab** compared to **deucravacitinib** in adult subjects with moderate plaque psoriasis who are candidates for systemic therapy. The primary efficacy endpoints include the achievement of PASI 90, defined as a ≥ 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI), and a static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-grade improvement from baseline. These endpoints will be evaluated at Week 16 for Period A and at Week 52 for Period B among subjects who switch from deucravacitinib to risankizumab after failing to achieve PASI 90 at Week 16.

Secondary efficacy endpoints include the achievement of PASI 100 and sPGA 0 with at least a 2-grade improvement from baseline at Week 16 for Period A, and at Week 52 for Period B among subjects switching treatments. Efficacy assessments will be conducted using validated scales such as PASI and sPGA at specified timepoints, including Week 16 and Week 52. The trial is designed as a Phase 4, multicenter, randomized, open-label, efficacy assessor-blinded study, ensuring objective evaluation of the treatment outcomes.