A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants with Active Systemic Lupus Erythematosus (SLE) (POETYK SLE-2)

The primary objective of this study is to demonstrate the **superiority** of deucravacitinib compared to placebo in the treatment of participants with active **Systemic Lupus Erythematosus (SLE)**, specifically with respect to the SLE Responder Index (SRI) (4). This is clinically relevant as it aims to establish the efficacy of deucravacitinib in improving disease outcomes in SLE, a chronic autoimmune condition with significant morbidity.

Secondary objectives include: - Evaluating the efficacy of deucravacitinib compared to placebo on additional measures of clinical disease activity. - Assessing fatigue status in participants with active SLE. - Evaluating the safety and tolerability of deucravacitinib in participants with active SLE. These objectives are crucial for understanding the broader impact of the treatment on patient quality of life and its safety profile.

The clinical trial involves a total of **369 participants** diagnosed with **Active Systemic Lupus Erythematosus (SLE)**. The study population includes both male and female participants aged between 18 and 75 years. Participants were selected based on their diagnosis of SLE at least 24 weeks prior to screening and must meet the European Alliance of Associations for Rheumatology/American College of Rheumatology 2019 classification criteria for SLE. They are required to test positive for at least one lupus-related autoantibody, such as antinuclear antibodies (ANA) ≥ 1:80, anti-dsDNA antibody, or anti-Smith (anti-Sm). Participants must exhibit active lupus with a total SLEDAI-2K score of ≥ 6 points and a clinical SLEDAI-2K score of ≥ 4 points, including joint involvement, cutaneous vasculitis, or rash. The trial population is on stable background therapy with anti-malarial agents and/or immunosuppressants, and may also be on corticosteroids. The study includes a vulnerable population, ensuring comprehensive representation of individuals affected by SLE.

The clinical trial is designed to evaluate the **efficacy** and safety of **deucravacitinib** in participants with active **Systemic Lupus Erythematosus (SLE)**. This is a Phase 3, randomized, double-blind, placebo-controlled study. The trial aims to demonstrate the superiority of deucravacitinib compared to placebo in treating participants with SLE, with the primary endpoint being the proportion of participants achieving an SRI(4) response at Week 52. Secondary endpoints include the proportion of participants achieving a BICLA response, dual responders, and other clinical measures at Week 52.

The trial is expected to last until December 2027, with recruitment starting in May 2023. Participants will be involved for a maximum treatment period of 104 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and disease activity; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to assess final outcomes. Participants must be on stable background therapy with anti-malarial agents and/or immunosuppressants, and may also be on corticosteroids.

Inclusion criteria require participants to be aged 18 to 75, diagnosed with SLE at least 24 weeks prior to screening, and meeting specific classification criteria. Participants must test positive for lupus-related autoantibodies and have active lupus as defined by SLEDAI-2K scores. Conditions for early termination from the study include adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial is not categorized as low intervention and involves the administration of deucravacitinib in the form of film-coated tablets for oral use, with a maximum daily dose of 6 mg.

The clinical trial involves the administration of **deucravacitinib**, an experimental medication, to evaluate its efficacy and safety in participants with active Systemic Lupus Erythematosus (SLE). Deucravacitinib is provided in the form of a **film-coated tablet** and is intended for **oral use**. The maximum daily dose of deucravacitinib is 6 mg, with a total maximum dose of 4368 mg over the course of the study. The treatment period extends up to 104 weeks. The active substance, deucravacitinib, is of chemical origin and is developed by Bristol-Myers Squibb International Corporation. The medication is identified by the sponsor product code BMS-986165.

In addition to the experimental treatment, a **placebo** is utilized in this study to serve as a comparator. The placebo is also provided in the form of film-coated tablets for oral use. The placebo is designed to match the experimental medication in appearance to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of deucravacitinib's efficacy by comparing outcomes between the active treatment group and the placebo group.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The study is conducted under a randomized, double-blind, placebo-controlled design to objectively evaluate the superiority of deucravacitinib over the placebo in treating participants with SLE, as measured by the SLE Responder Index (SRI) (4).

The efficacy of deucravacitinib in the treatment of active **Systemic Lupus Erythematosus (SLE)** will be assessed through a series of predefined endpoints in a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint is the proportion of participants achieving a Systemic Lupus Erythematosus Responder Index (SRI) (4) response at Week 52. Secondary endpoints include the proportion of participants achieving a BICLA response at Week 52, dual responders achieving both SRI(4) and BICLA, and those with a baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10 achieving a ≥ 50% reduction from baseline at Week 52.

Additional secondary endpoints involve the proportion of participants on ≤ 7.5 mg per day of corticosteroids at Week 24 without dose increase to Week 52, and those with ≥ 6 active joints at baseline achieving at least a 50% reduction in active joints at Week 52. Patient-reported outcomes will be measured by changes in fatigue using the FACIT-Fatigue scale at Week 52. Safety and tolerability will be monitored through the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events leading to discontinuation, as well as changes from baseline in laboratory tests, electrocardiograms (ECGs), and vital signs.