Efficacy and Safety Evaluation of Efgartigimod Alfa Subcutaneous Injection in Adult Patients with Primary Sjögren’s Disease: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of efgartigimod PH20 subcutaneous (SC) compared with placebo PH20 SC on systemic disease activity in patients with **Primary Sjögren’s Disease**. This is measured by the clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (clinESSDAI). Assessing the efficacy of efgartigimod PH20 SC is clinically relevant as it may offer a novel therapeutic option for managing systemic disease activity in this patient population, potentially improving clinical outcomes and quality of life.

Secondary objectives include evaluating the efficacy of efgartigimod PH20 SC compared with placebo PH20 SC on: - Systemic disease activity using both clinESSDAI and ESSDAI. - A composite measure known as STAR (Sjogren's Tool for Assessing Response). - Symptom severity using the DiSSA, a patient-reported outcome (PRO) measure.

The clinical trial involves a total of **372 participants** diagnosed with **Primary Sjögren’s Disease**. The study population includes both male and female subjects, aged 18 years and older, who meet specific criteria such as the ACR/EULAR classification criteria 2016 for primary Sjögren’s Disease, a clinESSDAI score of 6 or higher, and are Anti-Ro/SS-A positive. Participants must also have an unstimulated residual salivary flow of at least 0.01 mL/min. The trial does not include a vulnerable population. Selection of participants was based on these criteria to ensure a representative sample of individuals affected by the disease. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The trial aims to evaluate the efficacy of efgartigimod PH20 SC compared with placebo PH20 SC on systemic disease activity.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of **efgartigimod** administered subcutaneously in adult patients with **Primary Sjögren’s Disease**. The trial includes an open-label extension phase and is expected to conclude by July 31, 2028. The study will commence recruitment on April 21, 2025, and will involve a series of structured visits over the course of the trial.

Participants will be randomly assigned to receive either efgartigimod or a placebo, both administered via subcutaneous injection using a pre-filled syringe. The primary objective is to assess the change from baseline in the clinESSDAI score at week 48. Secondary endpoints include changes in ESSDAI scores, the proportion of participants achieving low disease activity, and other clinically relevant measures at specified intervals.

The trial will begin with a screening visit to confirm eligibility based on criteria such as age, disease classification, and specific laboratory markers. Following randomization, participants will attend regular follow-up visits to monitor treatment effects and safety. These visits will include assessments of systemic disease activity, joint pain, and other symptoms associated with Primary Sjögren’s Disease. The end-of-study visit will occur at the conclusion of the treatment period, which is set at a maximum of 96 weeks.

Participant involvement is expected to last for the duration of the trial, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study protocols. The trial is designed to ensure rigorous monitoring and data collection to support the evaluation of efgartigimod's therapeutic potential in this patient population.

The clinical trial involves the administration of **Efgartigimod**, a solution for injection in a pre-filled syringe. The active substance in this experimental medication is **efgartigimod alfa**, a protein of human monoclonal origin, specifically an anti-FcRn receptor fragment. The pharmaceutical form is a solution intended for subcutaneous injection. The maximum daily dose is 1000 mg, with a total maximum dose of 95000 mg over a treatment period of 96 weeks. The administration is conducted via subcutaneous injection, and the medication is provided by ARGENX BV. Participant compliance is monitored through scheduled dosing and adherence checks.

The trial also includes a **placebo** treatment, which is designed to match the investigational medicinal product (IMP) in appearance and administration method. The placebo is administered subcutaneously, similar to the experimental treatment, to maintain the double-blind nature of the study. The placebo serves as a comparator to evaluate the efficacy and safety of Efgartigimod in patients with primary Sjögren’s Disease. Compliance with the placebo administration is similarly monitored to ensure the integrity of the trial results.

The efficacy of the investigational product, **Efgartigimod**, will be assessed in a Phase 3 randomized, double-blinded, placebo-controlled multicenter trial with an open-label extension. The primary endpoint for evaluating efficacy is the change from baseline in the clinESSDAI score at week 48. Secondary endpoints include the change from baseline in the ESSDAI score at week 48, the proportion of participants with low disease activity (clinESSDAI < 5) at week 48, and the proportion of responders on the STAR (defined as ≥ 5 points) at week 48. Additional secondary endpoints involve changes from baseline in the DiSSA joint pain item, DiSSA total score, and DiSSA sicca domain at week 48, as well as the proportion of participants with minimal clinically important improvement (MCII) in ESSDAI (defined as an improvement of ≥ 3 points) at week 48, and the change from baseline in clinESSDAI score at week 24.

The clinESSDAI and ESSDAI scores are utilized to measure systemic disease activity in patients with Primary Sjögren’s Disease. These scores will be collected and analyzed at specified timepoints, including week 24 and week 48, to determine the efficacy of the treatment. The trial aims to compare the efficacy of subcutaneous administration of Efgartigimod PH20 with placebo PH20, using these validated scales to ensure accurate and reliable assessment of disease activity and patient response.