Efficacy and Safety Evaluation of Deucravacitinib in Biologic-Naïve Patients with Active Psoriatic Arthritis: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to compare the **efficacy** of deucravacitinib to placebo in the treatment of participants with active **Psoriatic Arthritis** (PsA). This is clinically relevant as it aims to establish the therapeutic potential of deucravacitinib, a novel treatment option, for patients who are naïve to biologic disease-modifying anti-rheumatic drugs, potentially offering a new avenue for managing this chronic inflammatory condition.

Secondary objectives include:

• Comparing the efficacy of deucravacitinib to placebo at Week 16 as assessed by DAS28-CRP.
• Comparing the efficacy as assessed by HAQ-DI score at Week 16.
• Comparing the efficacy as assessed by PASI 75 response at Week 16.
• Comparing the efficacy as assessed by SF-36 PCS score at Week 16.
• Comparing the efficacy in enthesitis resolution at Week 16.
• Comparing the efficacy in MDA response at Week 16.
• Comparing the efficacy in FACIT-Fatigue score at Week 16.
• Comparing the efficacy in dactylitis resolution at Week 16.
• Comparing the efficacy as assessed by structural damage at Week 16.

The clinical trial involves a total of **324 participants** diagnosed with **active psoriatic arthritis**. 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 criteria, including a diagnosis of psoriatic arthritis for at least three months, meeting the Classification Criteria for Psoriatic Arthritis (CASPAR), and having active plaque psoriatic skin lesions or a documented history of plaque psoriasis. Additionally, participants exhibit active arthritis with at least three swollen and tender joints, a high sensitivity C-reactive protein level of 3 mg/L or higher, and at least one PsA-related joint erosion confirmed by X-ray. The trial population includes individuals from a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed. The selection process ensures a representative sample of individuals with the condition, allowing for a comprehensive evaluation of the treatment's efficacy.

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 **psoriatic arthritis** who are naïve to biologic disease-modifying anti-rheumatic drugs. The trial aims to compare the efficacy of deucravacitinib to placebo in treating participants with active psoriatic arthritis. The study is expected to run from July 2021 to September 2027, with a maximum treatment period of 156 weeks for each participant. Participants will be randomly assigned to receive either deucravacitinib or a placebo, both administered as film-coated tablets for oral use.

The trial includes several key study visits. The initial inclusion visit, or screening, will confirm eligibility based on criteria such as a diagnosis of psoriatic arthritis for at least three months, active arthritis, and specific laboratory markers. Participants must meet the Classification Criteria for Psoriatic Arthritis (CASPAR) and have active plaque psoriatic skin lesions or a documented history of plaque psoriasis. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse effects. The primary endpoint is the proportion of participants achieving an American College of Rheumatology improvement of 20% (ACR 20) response at Week 16. Secondary endpoints include changes in various clinical scores and the resolution of specific symptoms by Week 16.

The end-of-study visit will assess the overall outcomes and safety of the treatment. Participants' involvement is expected to last up to 156 weeks, depending on their response to the treatment and adherence to the study protocol. Conditions that may lead to early termination from the study include significant adverse reactions, non-compliance with study procedures, or withdrawal of consent by the participant. The trial is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound, as the experimental medication. 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 pharmaceutical form is a film-coated tablet, and the medication is administered orally. The maximum daily dose is 6 mg, with a total maximum dose of 6552 mg over a treatment period of 156 days. The trial is designed to evaluate the efficacy and safety of deucravacitinib in participants with active **psoriatic arthritis** who are naïve to biologic disease-modifying anti-rheumatic drugs.

The study also includes a **placebo** group to match the deucravacitinib tablet. The placebo is designed to be indistinguishable from the active treatment in appearance and is administered in the same manner, orally, to maintain the double-blind nature of the trial. The placebo serves as a comparator to assess the efficacy of deucravacitinib by providing a baseline for evaluating the treatment's effects. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The efficacy of deucravacitinib in the treatment of active **Psoriatic Arthritis** (PsA) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants achieving an American College of Rheumatology improvement of 20% (ACR 20) response at Week 16. Secondary endpoints include changes from baseline in the Disease Activity Score 28-C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at Week 16. Additionally, the study will evaluate the proportion of participants achieving a Psoriasis Area and Severity Index 75 (PASI 75) response, enthesitis resolution, and minimal disease activity (MDA) at Week 16. Other secondary measures include changes in the Short Form-36 Physical Component Summary (SF-36 PCS) score, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score, and PsA-modified Sharp/van der Heijde (SvdH) score at Week 16, as well as dactylitis resolution among participants with baseline dactylitis.