A Phase 3 Randomized Double-Blind Trial of Risankizumab Versus Placebo in Patients with Active Psoriatic Arthritis and Prior Biologic Therapy Inadequacy

The primary objective of this Phase 3, randomized, double-blind study is to compare the **efficacy** of risankizumab 150 mg versus placebo in the treatment of signs and symptoms of **Psoriatic Arthritis** (PsA) in the study population. This is clinically relevant as it aims to establish the therapeutic benefit of risankizumab in managing PsA, particularly for patients with a history of inadequate response or intolerance to biologic therapies.

Secondary objectives include:

• Period 1 Double-Blind: To compare the **safety** and **tolerability** of risankizumab 150 mg versus placebo in the study population.
• Period 2 Open-Label: To evaluate the long-term safety, tolerability, and **efficacy** of risankizumab 150 mg in subjects who have completed Period 1.

The clinical trial involves a total of **200 participants** diagnosed with **Psoriatic Arthritis**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on a clinical diagnosis of Psoriatic Arthritis with symptom onset at least six months prior to the screening visit, and they must fulfill the Classification Criteria for Psoriatic Arthritis (CASPAR) at the screening visit. Additionally, subjects are required to have active disease at baseline and a diagnosis of active plaque psoriasis with at least one psoriatic plaque of ≥ 2 centimeters in diameter or nail changes consistent with psoriasis at the screening visit. The trial population includes individuals who have demonstrated an inadequate response or intolerance to biologic therapies or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The study does not specify particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of all participants.

The clinical trial is a **Phase 3**, randomized, double-blind, controlled study designed to evaluate the efficacy of **risankizumab** compared to placebo in subjects with active **psoriatic arthritis**. The trial aims to assess the treatment's impact on the signs and symptoms of the disease, particularly in individuals with a history of inadequate response or intolerance to biologic therapies. The study is expected to span from July 2019 to April 2026, with a maximum treatment period of 336 days for each participant.

Participants will be randomly assigned to receive either risankizumab or a placebo, administered as a solution for injection in a pre-filled syringe via the subcutaneous route. The primary endpoint is the proportion of subjects achieving an American College of Rheumatology (ACR)20 response at Week 24. Secondary endpoints include changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriasis Area Severity Index (PASI) 90 response, and other measures of disease activity and quality of life at various time points.

The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as a clinical diagnosis of psoriatic arthritis and active disease at baseline, followed by regular follow-up visits to monitor treatment efficacy and safety. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events. Participants may be withdrawn from the study early if they experience significant adverse effects or if they do not adhere to the study protocol.

Inclusion criteria require participants to have a clinical diagnosis of psoriatic arthritis with symptom onset at least six months prior to the screening visit, active disease at baseline, and a history of inadequate response or intolerance to previous therapies. The trial's design ensures rigorous assessment of the investigational product's efficacy and safety, contributing valuable data to the understanding of treatment options for psoriatic arthritis.

The clinical trial involves the administration of **Risankizumab**, a solution for injection in a pre-filled syringe, with a concentration of 90 mg/mL. The active substance, risankizumab, is a protein of other origin. The pharmaceutical form is a solution for injection, and the route of administration is subcutaneous. The maximum daily dose is 150 mg, with a total maximum dose of 4350 mg over a treatment period of 336 days. The product is manufactured by ABBVIE DEUTSCHLAND GMBH & CO. KG and ABBVIE, INC. The trial aims to evaluate the efficacy of risankizumab in treating signs and symptoms of active psoriatic arthritis.

A placebo, designed to mimic the risankizumab solution for injection, is also used in this study. The placebo is administered subcutaneously in the same manner as the active treatment. The placebo is intended to serve as a control to assess the efficacy of risankizumab by providing a baseline for comparison. The placebo does not contain the active substance risankizumab and is used to maintain the double-blind nature of the study.

The efficacy of the investigational product, **risankizumab**, will be assessed in a Phase 3, randomized, double-blind clinical trial comparing it to a placebo in subjects with active psoriatic arthritis. The primary endpoint for evaluating efficacy is the proportion of subjects achieving an American College of Rheumatology (ACR)20 response at Week 24. Secondary endpoints include changes from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24, the proportion of subjects achieving a Psoriasis Area Severity Index (PASI) 90 response at Week 24 for those with a body surface area (BSA) ≥ 3% at baseline, and the proportion of subjects achieving ACR20 at Week 16. Additional secondary endpoints involve the proportion of subjects achieving Minimal Disease Activity (MDA) at Week 24, changes from baseline in the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Week 24, and changes from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT Fatigue) Questionnaire at Week 24. Further assessments include the proportion of subjects achieving ACR50 and ACR70 responses at Week 24, and the resolution of enthesitis and dactylitis at Week 24 in subjects with these conditions at baseline.