Phase 3 Randomized Double-Blind Study of Subcutaneous Sonelokimab in Biologic DMARD-Naive Adults with Active Psoriatic Arthritis

The primary objective of this study is to evaluate the **efficacy** of sonelokimab 60 mg administered every four weeks, with and without an induction regimen, at Week 16 compared to placebo, using ACR50 response criteria in participants with active **psoriatic arthritis**. This is clinically relevant as achieving an ACR50 response indicates a significant reduction in disease activity, which is crucial for improving patient outcomes in psoriatic arthritis.

Secondary objectives include:

• Evaluating the efficacy of sonelokimab 60 mg every four weeks, with and without an induction regimen, at Week 16 compared to placebo in participants with active psoriatic arthritis.
• Assessing the safety and tolerability of sonelokimab 60 mg every four weeks, with and without an induction regimen, over time in the treatment of participants with active psoriatic arthritis.

The clinical trial involves a total of **370 participants** diagnosed with **psoriatic arthritis**. The study population includes both male and female subjects, aged 18 years and older, who have been confirmed to meet the 2006 Classification for Psoriatic Arthritis (CASPAR) criteria. Participants exhibit moderate to severe active disease and have a history of inadequate response to at least one nonbiological conventional DMARD or NSAID, or have documented intolerance or contraindications to these treatments. The trial population was selected based on their ability to adhere to the protocol and their understanding of the informed consent process. Participants are required to have active plaque psoriasis or a personal history of plaque psoriasis, and they must test negative for rheumatoid factor and anti-cyclic citrullinated peptide. Lifestyle considerations such as diet and physical activity are not specified, but participants must be reliable in adhering to the study's medication intake and visit schedule. The trial includes both vulnerable populations and individuals who are not pregnant or breastfeeding, with women of childbearing potential agreeing to use highly effective contraception methods during the study and for a specified period after the last dose of the study treatment.

The clinical trial is a **Phase 3**, parallel-group, randomized, double-blind, 3-arm, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of subcutaneous **sonelokimab** in participants with active **psoriatic arthritis** who are naive to biologic DMARDs. The trial aims to assess the efficacy of sonelokimab 60 mg administered every four weeks, with and without an induction regimen, compared to a placebo, using ACR50 response criteria at Week 16. The primary endpoint is the proportion of participants achieving ACR50 at Week 16, while secondary endpoints include ACR20, Minimal Disease Activity, changes in Health Assessment Questionnaire—Disability Index, and other clinical measures.

The trial is expected to commence recruitment on May 2, 2025, and conclude by December 19, 2026. Participants will be involved in the study for a maximum treatment period of 56 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and disease activity; baseline assessments; regular follow-up visits to monitor efficacy and safety; and an end-of-study visit to evaluate overall outcomes. Participants may be withdrawn from the study early due to adverse events, non-compliance with the protocol, or withdrawal of consent.

Inclusion criteria require participants to be at least 18 years old, have a confirmed diagnosis of psoriatic arthritis per the CASPAR criteria, and exhibit moderate to severe active disease. Exclusion criteria are not specified in the provided data. The study will utilize a placebo, a sterile solution in a single-use prefilled syringe intended for subcutaneous administration, alongside the investigational product, sonelokimab, which is a nanobody that inhibits IL-17A and IL-17F. The trial is not classified as low intervention and is conducted under the sponsorship of Moonlake Immunotherapeutics AG.

The clinical trial involves the administration of **Sonelokimab**, an investigational medication, which is a **nanobody** that inhibits **IL-17A** and **IL-17F**. Sonelokimab is provided in the form of an **injection** and is administered via **subcutaneous injection**. The dosage regimen for Sonelokimab is 60 mg every four weeks (Q4W), with a maximum daily dose of 60 mg and a total maximum dose of 900 mg over a treatment period of 56 days. The pharmaceutical form is a sterile solution intended for subcutaneous administration, and the product is manufactured by Moonlake Immunotherapeutics AG. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

The study also includes a **placebo** group, which serves as a comparator to evaluate the efficacy and safety of Sonelokimab. The placebo is a sterile solution provided in a single-use prefilled syringe, also intended for subcutaneous administration. The placebo is administered following the same schedule as Sonelokimab, ensuring a double-blind study design. The use of a placebo allows for the assessment of the true therapeutic effect of Sonelokimab by comparing outcomes between the active treatment and placebo groups.

The efficacy of **sonelokimab** in the treatment of active psoriatic arthritis will be assessed using the American College of Rheumatology 50 (ACR50) response criteria. The primary endpoint is the proportion of participants achieving ACR50, which indicates a ≥50% improvement in symptoms, at Week 16. Secondary endpoints include the proportion of participants achieving ACR20 (≥20% improvement) and Minimal Disease Activity (MDA) at Week 16. Additional secondary endpoints involve changes from baseline in the Health Assessment Questionnaire—Disability Index (HAQ-DI), the Psoriasis Area and Severity Index (PASI90) response, and the SF-36 Physical Component Summary (PCS) at Week 16. Structural joint and bone damage will be evaluated using the van der Heijde modified Total Sharp Score.

Efficacy assessments will be conducted at specified timepoints, with the primary analysis occurring at Week 16. The ACR response criteria, HAQ-DI, PASI90, and SF-36 PCS are validated scales used to measure symptom improvement and quality of life in patients with psoriatic arthritis. The van der Heijde modified Total Sharp Score will be used to assess changes in joint and bone structural damage. These assessments will be performed through clinical evaluations, patient-reported outcomes, and imaging studies as appropriate. Data collection and analysis will adhere to the trial protocol to ensure the reliability and validity of the efficacy outcomes.