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-1)

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 patients with active SLE, a condition characterized by systemic inflammation and multi-organ involvement.

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. - Assessing 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 ensuring the safety profile of the drug.

The clinical trial involves a total of **384 participants** diagnosed with **Active Systemic Lupus Erythematosus (SLE)**. The study population includes both male and female subjects, 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). The participants must exhibit active lupus with a total SLEDAI-2K score ≥ 6 points and a clinical SLEDAI-2K score ≥ 4 points, including joint involvement, cutaneous vasculitis, or rash. All participants are on stable background therapy with anti-malarial agents and/or immunosuppressants, and may also be on corticosteroids. The trial includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across diverse patient profiles.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **deucravacitinib** in participants with active **Systemic Lupus Erythematosus (SLE)**. 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 those with a significant reduction in CLASI activity score, among others. The trial is expected to run until December 2027, with recruitment starting in May 2023.

Participants will be involved in the study for a maximum treatment period of 156 weeks. The study visits are structured to include an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and active lupus status. Participants must have a total SLEDAI-2K score of at least 6 points and be on stable background therapy. Follow-up visits will occur regularly to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The study will utilize deucravacitinib in the form of film-coated tablets, administered orally, with a maximum daily dose of 6 mg. The trial is not classified as a low-intervention study, and it is not intended for pediatric populations. The study is sponsored by Bristol-Myers Squibb International Corporation, and the investigational product is identified by the sponsor product code BMS-986165.

The clinical trial involves the administration of **deucravacitinib**, an experimental medication, in the form of film-coated tablets. The active substance, deucravacitinib, is chemically synthesized and is provided by Bristol-Myers Squibb International Corporation. The pharmaceutical form of the medication is a film-coated tablet, intended for **oral use**. The maximum daily dose is 6 mg, with a total maximum dose of 6552 mg over a treatment period of 156 days. The dosing schedule is designed to ensure consistent administration, and participant compliance is monitored throughout the trial to maintain the integrity of the study data.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this double-blind, placebo-controlled study. The placebo is also provided in the form of film-coated tablets for oral use, ensuring that the administration method is consistent with the experimental treatment. The use of a placebo allows for the assessment of the efficacy and safety of deucravacitinib in participants with active **Systemic Lupus Erythematosus (SLE)**, as outlined in the study's main objective. Compliance with the placebo administration is similarly monitored to ensure the reliability of the trial results.

The efficacy of deucravacitinib in the treatment of **Systemic Lupus Erythematosus (SLE)** will be assessed through a series of primary and secondary endpoints. 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 of ≥10 achieving a ≥50% reduction from baseline at Week 52. Additional secondary endpoints involve the proportion of participants maintaining corticosteroid doses of ≤7.5 mg per day at Week 24 without exceeding protocol-specified limits by Week 52, and those with ≥6 active joints at baseline achieving at least a 50% reduction in active joints by Week 52.

Patient-reported outcomes will be measured by changes from baseline in fatigue according to the FACIT-Fatigue scale at Week 52. Safety and tolerability will be monitored through the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to treatment discontinuation, and study discontinuation, as well as changes from baseline and/or abnormalities in laboratory tests, electrocardiograms (ECGs), and vital signs. These efficacy parameters will be collected and analyzed at specified timepoints, with the primary analysis occurring at Week 52.