A Phase 3 Randomized Double-Blind Study of Risankizumab Versus Placebo in Patients with Active Psoriatic Arthritis and Inadequate Response to DMARD Therapy

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 provide evidence on the effectiveness of risankizumab in managing PsA, a chronic inflammatory condition that can significantly impact patients' quality of life.

Secondary objectives include:

• Period 1 Double-Blind: To compare the efficacy of risankizumab 150 mg versus placebo for the inhibition of progression of structural damage as assessed by radiographs in the study population.
• 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 with PsA who have completed Period 1.

The clinical trial for the treatment of **Psoriatic Arthritis** involves a total of 462 participants. 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 clinical diagnosis of Psoriatic Arthritis with symptom onset at least six months prior to the screening visit, and fulfillment of the Classification Criteria for Psoriatic Arthritis (CASPAR). Additionally, subjects must 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. The trial does not include a vulnerable population. Participants were required to have demonstrated an inadequate response to previous or current treatment with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) at a maximally tolerated dose. Lifestyle considerations such as diet, physical activity, or habits were not specified by the sponsor.

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** who have shown an inadequate response or intolerance to at least one disease-modifying anti-rheumatic drug (DMARD) therapy. The trial is expected to run from July 30, 2019, to July 29, 2026, with a maximum treatment period of 336 days for each participant. The study involves the administration of risankizumab as a solution for injection in a pre-filled syringe via subcutaneous use, with a maximum daily dose of 150 mg and a total dose not exceeding 4350 mg.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of psoriatic arthritis, active disease at baseline, and a history of inadequate response to csDMARDs. Following the screening, participants will be randomized to receive either risankizumab or placebo. The primary endpoint is the proportion of subjects achieving an ACR 20 response at Week 24. Secondary endpoints include changes in the Health Assessment Questionnaire – Disability Index, PASI 90 response, and other measures of disease activity and quality of life at various time points, including Weeks 16 and 24.

Study visits will include regular follow-up assessments to monitor efficacy and safety, with the end-of-study visit marking the conclusion of the participant's involvement. The expected length of participant involvement is approximately 24 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **risankizumab**, an experimental medication, which is provided as a **solution for injection in a pre-filled syringe**. The pharmaceutical form is designed for **subcutaneous use**. The dosage of risankizumab is set at 150 mg, with a maximum total dose amounting to 4350 mg over the course of the treatment period, which spans 336 days. The administration schedule is structured to ensure optimal efficacy and safety, with compliance monitored throughout the trial duration. Risankizumab is a protein-based therapeutic agent, specifically categorized under "Protein - Other," and is developed by ABBVIE DEUTSCHLAND GMBH & CO. KG and ABBVIE, INC.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is designed to mimic the risankizumab solution for injection in pre-filled syringes, ensuring blinding in the double-blind study design. The placebo does not contain any active substance and is administered following the same route and schedule as the experimental medication to maintain consistency in the trial protocol.

The efficacy of the investigational product, **risankizumab**, will be assessed in a Phase 3, randomized, double-blind clinical trial involving subjects with active Psoriatic Arthritis (PsA) who have shown inadequate response or intolerance to at least one Disease Modifying Anti-Rheumatic Drug (DMARD) therapy. The primary endpoint for evaluating efficacy is the proportion of subjects achieving an 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 PASI 90 response at Week 24 in 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 modified Nail Psoriasis Severity Index (mNAPSI) and Physician Global Assessment of Fingernail Psoriasis (PGA-F) at Week 24 in subjects with nail psoriasis at baseline, and the resolution of enthesitis and dactylitis at Week 24 in subjects with these conditions at baseline. Further assessments include changes from baseline in the modified Total Sharp Score (PsA mTSS), 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire at Week 24, as well as the proportion of subjects achieving ACR50 and ACR70 responses at Week 24.