Efficacy and Safety of Subcutaneous Guselkumab in Bio-naive Patients with Active Psoriatic Arthritis Axial Disease: A Phase 4 Randomized, Double-blind, Placebo-controlled Study

The primary objective of this study is to evaluate the **efficacy** of guselkumab in reducing axial symptoms in participants with active **Psoriatic Arthritis** (PsA) axial disease. This is clinically relevant as it aims to provide evidence on the effectiveness of guselkumab, a monoclonal antibody, in managing axial symptoms, which are a significant component of PsA and can severely impact patient quality of life. The study is designed as a Phase 4, multicenter, randomized, double-blind, placebo-controlled trial, ensuring robust data on the therapeutic potential of guselkumab when administered subcutaneously to bio-naive subjects.

The clinical trial involves a total of **172 participants** diagnosed with **Psoriatic Arthritis** (PsA), specifically focusing on those with active PsA axial disease. The study population includes both male and female subjects, aged 18 years and older, who meet the ClASsification criteria for Psoriatic ARthritis (CASPAR) and have been diagnosed with PsA for at least six months prior to the study. Participants were selected based on their active PsA status, characterized by at least three swollen and tender joints, a C-reactive protein level of ≥0.3 mg/dL, and a BASDAI score of at least 4. Additionally, participants must have magnetic resonance imaging-confirmed PsA axial disease and a spinal pain score of at least 4. The trial also considers lifestyle factors such as previous non-biologic DMARD, apremilast, and/or NSAID therapy, as participants must have active PsA despite these treatments. The study includes individuals with active plaque psoriasis, either with psoriatic plaques of ≥2 cm in diameter, nail changes consistent with psoriasis, or a documented history of plaque psoriasis. The trial population is inclusive of vulnerable populations, ensuring a comprehensive evaluation of the efficacy of guselkumab treatment in reducing axial symptoms in this specific patient group.

The clinical trial is a **Phase 4**, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **guselkumab** administered subcutaneously in bio-naive subjects with active **psoriatic arthritis** axial disease. The trial aims to assess the reduction in axial symptoms over a period of 48 weeks. Participants will be randomly assigned to receive either guselkumab or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

The trial will commence with an inclusion (screening) visit, where potential participants will be evaluated against the inclusion criteria, which include being at least 18 years of age, having a diagnosis of psoriatic arthritis for at least six months, and meeting the CASPAR criteria. Participants must also have active psoriatic arthritis, as defined by specific clinical and laboratory parameters, and confirmed axial disease via magnetic resonance imaging. Following successful screening, eligible participants will be enrolled and randomized into the study.

Study visits will occur at regular intervals throughout the trial duration, with key assessments conducted at baseline and at Week 24, which is the primary endpoint for evaluating changes in the BASDAI score. Follow-up visits will monitor the safety and efficacy of the treatment, with adjustments made as necessary based on participant response and any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall outcomes of the intervention.

Participant involvement is expected to last for the entire 48-week period unless early termination is warranted. Conditions that may lead to early termination include significant adverse reactions, withdrawal of consent, or non-compliance with study protocols. The trial is structured to ensure rigorous monitoring and data collection, contributing to the understanding of guselkumab's role in managing psoriatic arthritis axial disease.

The clinical trial involves the administration of **Guselkumab**, a monoclonal antibody, as the experimental treatment. Guselkumab is provided as a solution for injection in a pre-filled syringe, with a concentration of 100 mg/mL. The pharmaceutical form is designated as **INJECTION/INFUSION**. The route of administration is **subcutaneous use**, and the treatment is delivered using a 1 mL UltraSafe Plus™ Passive Needle Guard, which facilitates manual injection and enables passive activation of a needle guard post-delivery. The maximum treatment period for Guselkumab is 48 weeks. The active substance, Guselkumab, is a protein of other origin, and the product is manufactured by Janssen-Cilag International N.V.

The study also includes a placebo comparator, identified as Guselkumab 1 mL PFS Placebo. The placebo is administered in the same manner as the active treatment, using a pre-filled syringe for subcutaneous injection. The placebo is designed to match the experimental treatment in appearance and administration to maintain the double-blind nature of the study. The placebo does not contain the active substance Guselkumab, ensuring that any observed effects can be attributed to the active treatment. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The efficacy of guselkumab in the treatment of active **Psoriatic Arthritis** (PsA) with axial disease will be assessed in a Phase 4, multicenter, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24. This index is a validated scale used to measure the severity of symptoms in patients with axial spondyloarthritis, including PsA.

Participants will be assessed for efficacy at various timepoints throughout the study, with the primary assessment occurring at Week 24. The BASDAI score, which ranges from 0 to 10, will be collected and analyzed to determine the reduction in axial symptoms. The trial aims to provide a comprehensive evaluation of guselkumab's impact on symptom improvement in bio-naive subjects with active PsA axial disease. The study will utilize a pre-filled syringe for subcutaneous administration of the drug, ensuring consistent dosing and delivery.