Efficacy and Safety of Subcutaneous Guselkumab in Active Psoriatic Arthritis: A Phase 3b Randomized, Double-blind, Placebo-controlled Study

The primary objective of this study is to evaluate the **efficacy** of guselkumab treatment in participants with active **psoriatic arthritis** (PsA) by assessing the reduction in signs and symptoms of PsA. This is clinically relevant as it aims to determine the therapeutic potential of guselkumab in alleviating the clinical manifestations of PsA, which can significantly impact patients' quality of life. The study also seeks to assess the safety profile of guselkumab, ensuring that the treatment is not only effective but also safe for long-term use in this patient population.

The clinical trial involves a total of **548 participants** diagnosed with **psoriatic arthritis (PsA)**. The study population includes both male and female subjects, aged 18 years and older, who are experiencing active PsA despite previous treatments with non-biologic DMARDs, apremilast, and/or NSAIDs. Participants were selected based on specific criteria, including having a diagnosis of PsA for at least six months and meeting the CASPAR criteria at screening. The trial population is characterized by individuals with active plaque psoriasis and at least one psoriatic plaque of ≥ 2 cm in diameter or nail changes consistent with psoriasis. Participants may be using non-biologic DMARDs, NSAIDs, or oral corticosteroids, provided the doses are stable for a specified period before the study intervention. The trial also includes individuals with at least three swollen and tender joints and a CRP level of ≥ 0.3 mg/dL at screening. The study considers lifestyle factors such as the stability of medication doses and the presence of specific PsA subsets, including distal interphalangeal joint involvement and polyarticular arthritis. The trial does not exclude vulnerable populations, ensuring a comprehensive assessment of the treatment's efficacy across diverse demographic groups.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of **guselkumab** in participants with active **psoriatic arthritis** (PsA). The trial aims to assess the reduction in signs and symptoms of PsA and inhibit radiographic progression. The study involves the administration of guselkumab via **subcutaneous injection** and includes a placebo group for comparison. The trial is expected to run from September 2021 to March 2028, with a total duration of approximately 6.5 years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, previous treatment history, and disease activity. Following successful screening, participants will be randomized to receive either guselkumab or placebo. The primary endpoint is the proportion of participants achieving an American College of Rheumatology (ACR) 20 response at Week 24. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted.

The expected length of participant involvement is up to 156 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The study is structured to ensure rigorous data collection and analysis, maintaining the integrity of the trial's objectives and outcomes.

The clinical trial involves the administration of **Guselkumab**, a solution for injection in a pre-filled syringe, with a concentration of 100 mg/mL. This experimental medication is designed for **subcutaneous use** and is provided by Janssen-Cilag International N.V. The active substance, Guselkumab, is a protein of other origin. The medication is administered via injection or infusion, utilizing the UltraSafe Plus™ Passive Needle Guard, which facilitates manual injection and ensures passive activation of the needle guard post-delivery. The dosing schedule and frequency of administration are determined by the study protocol, with a maximum treatment period of 156 weeks. Participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen.

The study also includes a **placebo** treatment, which is a solution for injection in a pre-filled syringe, matching the Guselkumab formulation in appearance and administration method. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased assessment of Guselkumab's efficacy and safety. The placebo is administered following the same route and frequency as the experimental medication, with participant compliance similarly monitored to maintain the integrity of the study results.

The efficacy of guselkumab in the treatment of active **Psoriatic Arthritis** (PsA) will be assessed in a Phase 3b, multicenter, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants achieving an American College of Rheumatology (ACR) 20 response at Week 24. This endpoint measures a 20% improvement in tender and swollen joint counts, as well as a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein levels.

Participants will receive subcutaneous injections of guselkumab, and the efficacy assessments will be conducted at specified intervals throughout the study. The trial will utilize validated scales and laboratory tests to collect and analyze data on the reduction of PsA signs and symptoms. The study is designed to ensure rigorous evaluation of the treatment's impact on disease progression and symptom management, with the ultimate goal of determining the therapeutic benefit of guselkumab in this patient population.