A Multi-Center Study to Characterize the Long-Term Safety and Efficacy of BMS-986165 in Subjects with Systemic Lupus Erythematosus

The primary objective of this study is to characterize the long-term **safety** and tolerability of BMS-986165 in subjects with **Systemic Lupus Erythematosus** (SLE). This is clinically relevant as it aims to ensure that the therapeutic use of BMS-986165 does not result in adverse effects over extended periods, which is crucial for chronic conditions like SLE where long-term treatment is often necessary.

Secondary objectives include:

• **Efficacy**: To characterize the long-term maintenance of response of BMS-986165 in the treatment of subjects with SLE and to assess patient-reported outcomes during long-term therapy.
• **Pharmacokinetic**: To explore the long-term pharmacokinetics of BMS-986165, which involves understanding how the drug is absorbed, distributed, metabolized, and excreted over time.
• **Pharmacodynamic**: To explore the long-term pharmacodynamics of BMS-986165, focusing on the drug's effects on the body and its mechanism of action over prolonged use.

The clinical trial involves a total of **198 participants** diagnosed with **Systemic Lupus Erythematosus**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating a broad adult demographic. Participants were selected based on their completion of a prior study (IM011021) and their current receipt of a blinded study drug. The trial includes a vulnerable population, necessitating careful ethical considerations. Lifestyle factors such as diet and physical activity are not specified, but reproductive status is a significant consideration, with specific contraceptive requirements for women of childbearing potential and sexually active male participants. The primary objective of the trial is to assess the long-term safety and tolerability of BMS-986165 in this population.

The clinical trial is designed to evaluate the long-term safety and efficacy of **deucravacitinib** in subjects with **Systemic Lupus Erythematosus**. This is a Phase 4, multi-center study employing a randomized, double-blind, controlled trial design. The trial is expected to run from June 19, 2019, to March 31, 2025, with a maximum treatment period of 174 days for each participant. Participants will be randomly assigned to receive either deucravacitinib in varying doses (3 mg, 6 mg, or 12 mg) or a placebo, all administered orally in the form of film-coated tablets.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of a prior study (IM011021) and current receipt of a blinded study drug. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception. The primary endpoint focuses on monitoring adverse events, serious adverse events, vital signs, and laboratory parameters. Secondary endpoints include various efficacy measures such as CLASI response, joint count assessments, and pharmacokinetic and pharmacodynamic evaluations.

Participants will attend follow-up visits at regular intervals to assess safety and efficacy outcomes, with the end-of-study visit marking the conclusion of their involvement. The expected length of participant involvement is approximately 174 days, although early termination may occur due to adverse events, non-compliance, or withdrawal of consent. The trial aims to provide comprehensive data on the long-term use of deucravacitinib in managing systemic lupus erythematosus, contributing valuable insights into its safety profile and therapeutic potential.

The clinical trial involves the administration of **deucravacitinib**, a chemical entity, in the form of film-coated tablets. The experimental medication is provided in three different dosages: 3 mg, 6 mg, and 12 mg. Each tablet is designed for **oral use**. The maximum daily dose for the 3 mg tablet is 6 mg, while for the 6 mg and 12 mg tablets, it is 12 mg. The maximum total dose over the treatment period is 7,308 mg for the 3 mg tablet and 14,616 mg for both the 6 mg and 12 mg tablets. The treatment period extends up to 174 days. The active substance in these tablets is deucravacitinib, also known by its synonyms BMS986165 and 6-((cyclopropylcarbonyl)amino]-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-((2H3)methyl)pyridazine-3-carboxamide. The pharmaceutical form of the tablets is consistent across all dosages, ensuring uniformity in administration.

In addition to the experimental medication, a **placebo** is utilized in the study to match the deucravacitinib tablet. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring blinding in the trial. The placebo is administered orally, similar to the active treatment, and is used to assess the efficacy and safety of deucravacitinib by providing a baseline for comparison. The placebo does not contain any active substance and serves as a control to evaluate the true effects of the experimental drug.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. This monitoring is crucial for maintaining the integrity of the study results and for accurately assessing the long-term safety and efficacy of deucravacitinib in subjects with **Systemic Lupus Erythematosus** (SLE). The trial is conducted under the sponsorship of Bristol-Myers Squibb International Corporation, which is responsible for the development and provision of the investigational product.

The efficacy of BMS-986165 in subjects with **Systemic Lupus Erythematosus** will be assessed through a series of secondary endpoints. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) response, 40-joint count for tender, swollen, and tender + swollen joints, Systemic Lupus Erythematosus Responder Index (SRI(4)) response, and British Isles Lupus Assessment Group (BILAG) response. Additional measures include the Physician's Global Assessment (PGA), corticosteroid use and dose, flare analysis (time to first flare, number and frequency of flares, flares leading to hospitalization), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) total score, SLE Disease Activity Index 2000 (SLEDAI-2K) score, Lupus Low Disease Activity State (LLDAS) response, and the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a score.

Pharmacokinetic and pharmacodynamic parameters will also be evaluated, including plasma concentrations of BMS-986165 and levels of double-stranded DNA (dsDNA), C-reactive protein (CRP), complement levels, and urine protein-to-creatinine ratio (UPCR). These efficacy parameters will be collected and analyzed at various timepoints throughout the study to provide a comprehensive assessment of the drug's impact on disease activity and patient well-being.