Efficacy and Safety Evaluation of Deucravacitinib in Adults with Active Sjögren's Syndrome: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to compare the **efficacy** of deucravacitinib versus placebo in participants with active Sjögren's syndrome (SjS) by evaluating the improvement in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 52. This is clinically relevant as it aims to determine the potential of deucravacitinib to alleviate disease activity in SjS, a condition characterized by systemic autoimmune features that can significantly impact patient quality of life.

Secondary objectives include:

• Comparing the efficacy of deucravacitinib versus placebo in participants with active SjS using additional measures of clinical disease activity, organ function, and patient-reported outcomes at Week 52.
• Assessing the safety and tolerability of deucravacitinib in participants with active SjS up to Week 52.

The clinical trial involves a total of **512 participants** diagnosed with **Sjogren's syndrome**. The study population includes both male and female adults aged 18 years and older, with a focus on individuals who meet the 2016 American College of Rheumatology/European League Against Rheumatism criteria for the classification of Sjogren's syndrome. Participants are required to have moderate to severe disease, as indicated by an ESSDAI score of 5 or higher, and must test positive for the anti-SSA/Ro antibody. The trial population was selected based on specific inclusion criteria, including a disease duration of 10 years or less and a stimulated whole saliva flow rate of at least 0.05 mL/minute. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across diverse patient groups.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **deucravacitinib** in adults with active **Sjogren's syndrome**. The primary objective is to compare the efficacy of deucravacitinib versus placebo by assessing the improvement in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 52. The trial is expected to commence recruitment on January 10, 2024, and conclude by November 16, 2028. Participants will be randomly assigned to receive either deucravacitinib or a placebo, administered orally in the form of film-coated tablets.

The study will involve several key visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age (≥ 18 years), satisfaction of the 2016 American College of Rheumatology/European League Against Rheumatism criteria for Sjogren's syndrome, and a moderate to severe disease activity (ESSDAI ≥ 5). Participants must also be positive for anti-SSA/Ro antibody and have a disease duration of ≤ 10 years. Following the screening, eligible participants will undergo randomization and baseline assessments.

Throughout the trial, participants will attend regular follow-up visits to monitor their response to treatment and assess any adverse events. These visits will include evaluations of secondary endpoints such as changes in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Schirmer's test, and various symptom scores, including fatigue and dryness. Safety assessments will include monitoring for adverse events, serious adverse events, and any laboratory or vital sign abnormalities.

The expected duration of participant involvement is up to 52 weeks, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The end-of-study visit will involve a comprehensive assessment to evaluate the overall efficacy and safety of the treatment. The trial aims to provide valuable insights into the potential benefits of deucravacitinib for individuals with active Sjogren's syndrome, contributing to the development of effective therapeutic strategies for this condition.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound, 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, designed for oral use. The trial includes two different dosages of deucravacitinib, identified by the sponsor product code BMS-986165, with a maximum daily dose and total dose amount set at 9999 mg. The treatment period is capped at 156 weeks. The administration route is strictly oral, and the trial does not involve a pediatric formulation.

In addition to the experimental medication, the study employs a placebo control. The placebo is also provided in the form of film-coated tablets for oral use, available in 3 mg and 6 mg dosages. The placebo is designed to match the experimental medication in appearance to maintain the double-blind nature of the study. The placebo serves as a comparator treatment to evaluate the efficacy and safety of deucravacitinib in participants with active Sjögren’s Syndrome. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of deucravacitinib in the treatment of active **Sjögren’s Syndrome** will be assessed through a randomized, double-blind, placebo-controlled Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 52. Secondary endpoints include changes from baseline in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at Week 52, the proportion of participants with a decrease in ESSPRI by at least 1 point or 15% from baseline at Week 52, and the proportion of participants with a decrease in ESSDAI by at least 3 points from baseline at Week 52. Additional secondary endpoints involve the proportion of participants with an ESSDAI score of less than 5 at Week 52, changes from baseline in ESSDAI at Week 24, and changes from baseline in salivary flow rate (SWSF), Physician Global Assessment (PhGA), FACIT-Fatigue, and various numerical rating scales (NRS) for symptoms such as ocular dryness, oral dryness, and joint/muscle pain at Week 52.

Data collection will occur at specified timepoints, with the primary endpoint assessed at Week 52. The trial will utilize validated scales and patient-reported outcomes to measure these parameters. The incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events leading to discontinuation will also be monitored, alongside changes in laboratory tests, electrocardiograms (ECGs), and vital signs. The trial is designed to provide a comprehensive evaluation of the efficacy and safety of deucravacitinib in this patient population over a treatment period of up to 156 weeks.