Efficacy and Safety Evaluation of Deucravacitinib in Active Discoid and Subacute Cutaneous Lupus Erythematosus: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this Phase 2 randomized, double-blind, placebo-controlled study is to evaluate the effect of two doses of **deucravacitinib** (3 mg BID and 6 mg BID) compared with placebo on the CLASI-A score at Week 16 in participants with active Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE). The CLASI-A score is a clinically relevant measure as it quantifies the activity of cutaneous lupus erythematosus, providing insight into the efficacy of the treatment in reducing disease manifestations.

Secondary objectives include:

• To evaluate additional clinical measures of cutaneous disease manifestations with two doses of deucravacitinib (3 mg BID and 6 mg BID) compared with placebo at Week 16.
• To assess the safety and tolerability of two doses of deucravacitinib (3 mg BID and 6 mg BID) compared with placebo.

The clinical trial involves a total of **98 participants** diagnosed with **Active Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific inclusion criteria, such as having a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score of 8 or higher and currently receiving a stable treatment regimen for Cutaneous Lupus Erythematosus (CLE). The trial also considers vulnerable populations. Lifestyle factors such as diet, physical activity, and habits were not specified in the available data. The selection process ensures that participants are likely to benefit from the treatment, as determined by the investigator's medical judgment.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **deucravacitinib** in participants with active discoid and/or subacute cutaneous lupus erythematosus (DLE/SCLE). The trial aims to assess the effect of two doses of deucravacitinib (3 mg BID and 6 mg BID) compared with placebo on the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score at Week 16. The primary endpoint is the percentage change from baseline in the CLASI-A score. Secondary endpoints include the percentage of participants with an improvement of ≥ 50% from baseline in the CLASI-A score, mean change from baseline in CLASI-A score, and the number and proportion of participants experiencing serious adverse events (SAEs) and adverse events (AEs).

The trial is expected to last until May 2024, with participant recruitment having started in March 2021. Participants will be involved in the study for a maximum treatment period of 52 weeks. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to assess final outcomes. Participants must have a diagnosis of DLE/SCLE, a CLASI-A score of ≥ 8, and be on a stable treatment regimen for cutaneous lupus erythematosus to be eligible for inclusion. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with the study protocol.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound developed by Bristol-Myers Squibb International Corporation. Deucravacitinib is provided in the form of a **film-coated tablet**. The active substance, deucravacitinib, is chemically synthesized and is identified by the sponsor product code BMS-986165. The trial evaluates two dosing regimens: 3 mg and 6 mg, both administered orally twice daily (BID). The maximum daily dose is 12 mg, with a total maximum dose of 4368 mg over a treatment period of up to 52 weeks. The pharmaceutical form of the tablet ensures controlled release and absorption when taken orally.

In addition to the experimental medication, the study includes a **placebo** group to serve as a comparator. The placebo is designed to match the experimental treatment in appearance and administration route, ensuring blinding of participants and investigators. The placebo is administered orally with the same frequency as the active treatment, twice daily. This design allows for the assessment of deucravacitinib's efficacy and safety against a control group receiving no active therapeutic agent.

Participant compliance with the dosing schedule is monitored throughout the study. This is achieved through regular follow-up visits and the use of electronic diaries or pill counts to ensure adherence to the prescribed regimen. The study's primary objective is to evaluate the effect of deucravacitinib on the CLASI-A score at Week 16 in participants with active Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE).

The efficacy of **deucravacitinib** in the clinical trial will be assessed primarily through the percentage change from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score at Week 16. This primary endpoint will provide a quantitative measure of the drug's impact on disease activity in participants with active Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE).

Secondary endpoints will include several additional measures of efficacy: the percentage of participants achieving an improvement of ≥ 50% from baseline in the CLASI-A score (CLASI-50), the percentage of participants with a reduction in CLASI-A of ≥ 4 points from baseline, the mean change from baseline in CLASI-A score, and the percentage of participants achieving a Complete Response (CR) on CLASI-A, defined as a score of "0". These endpoints will further elucidate the therapeutic benefits of deucravacitinib.

Data collection will occur at specified timepoints, with the primary endpoint evaluated at Week 16. The trial will also monitor the number and proportion of participants experiencing serious adverse events (SAEs), adverse events (AEs) with severity and relationship to the treatment, and any abnormalities in laboratory testing, vital signs, and 12-lead ECGs. These assessments will ensure a comprehensive evaluation of both efficacy and safety throughout the study duration.