Open-Label Extension Study Evaluating Long-Term Safety of Efgartigimod Alfa in Adults with Primary Sjögren's Syndrome

The primary objective of this study is to evaluate the long-term **safety** of efgartigimod in patients with **Primary Sjögren's Syndrome** (pSS). This is clinically relevant as it aims to ensure that the therapeutic use of efgartigimod does not pose significant risks to patients over extended periods, which is crucial for chronic conditions like pSS.

Secondary objectives include:

• Evaluating the effect and assessing long-term data on the durability of CRESS (Composite of Relevant Endpoints for Sjögren's Syndrome) response.
• Evaluating the effect of efgartigimod on clinical efficacy parameters.
• Evaluating the effect of efgartigimod on STAR (Sjögren's Tool for Assessing Response).
• Assessing the pharmacodynamic (PD) effect of efgartigimod.
• Assessing the exposure to efgartigimod.
• Assessing the immunogenicity of efgartigimod.

The clinical trial focuses on evaluating the long-term safety of efgartigimod in patients with **Primary Sjögren's Syndrome**. The study population includes both male and female participants, with an age range starting from the legal age of consent for clinical trials. The trial involves a vulnerable population, although specific details regarding the total number of participants have not been provided by the sponsor. Participants were selected based on their completion of prior qualifying efgartigimod studies for Primary Sjögren's Syndrome and their agreement to continue treatment in the extension study. The trial requires participants to comply with protocol requirements, including the use of contraceptive measures as per local regulations. Lifestyle considerations such as diet, physical activity, or habits have not been specified in the available data.

The clinical trial is designed to evaluate the long-term safety of **efgartigimod alfa** in adult patients with **Primary Sjögren's Syndrome** (pSS) who have completed qualifying studies. This is an open-label extension study, meaning that both the researchers and participants are aware of the treatment being administered. The trial is categorized as a Phase 4 study, focusing on the safety profile of the investigational medicinal product (IMP) over an extended period. The trial is expected to last until January 21, 2025, with recruitment having commenced on August 15, 2023.

Participants will receive the IMP, **ARGX-113**, as a **solution for infusion** via intravenous administration. The maximum daily dose is set at 1200 mg, with a total maximum dose of 57600 mg over the 48-week treatment period. The study involves several key visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as legal age of consent, ability to provide informed consent, and completion of prior qualifying studies. Participants must also agree to use contraceptive measures and have a negative pregnancy test if applicable.

Throughout the trial, participants will attend follow-up visits to monitor the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and changes in laboratory test results, vital signs, and ECG results. Secondary endpoints include assessments of clinical response and disease activity using measures such as the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). The study will also evaluate changes in serum levels of total IgG and autoantibodies, as well as the presence of anti-drug antibodies (ADA) against efgartigimod.

The expected length of participant involvement is approximately 48 weeks, with conditions for early termination including the occurrence of significant adverse events or non-compliance with study protocols. The end-of-study visit will conclude the participant's involvement, ensuring all safety assessments are completed and any necessary follow-up care is arranged. This trial aims to provide comprehensive data on the safety and tolerability of efgartigimod in the target patient population.

The clinical trial involves the administration of **efgartigimod alfa**, an experimental medication, to evaluate its long-term safety in adult patients with primary Sjögren’s Syndrome (pSS). The investigational product, known as ARGX-113, is provided in the form of a **solution for infusion**. The pharmaceutical formulation is specifically designed for intravenous (IV) infusion. The maximum daily dose of efgartigimod alfa is 1200 mg, with a total maximum dose of 57600 mg over the course of the study. The treatment period extends up to 48 weeks, during which the medication is administered according to the specified dosing schedule. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The focus remains solely on the administration of efgartigimod alfa to assess its safety profile in the specified patient population. The investigational product is not a pediatric formulation and is not classified as an orphan drug. The active substance, efgartigimod alfa, is a protein-based therapeutic agent, specifically a human monoclonal antibody fragment targeting the FcRn receptor. This study does not involve any additional medicinal products or devices.

Efficacy in the clinical trial of **efgartigimod alfa** for primary Sjögren’s Syndrome (pSS) will be assessed using a range of primary and secondary endpoints. The primary endpoints focus on the incidence and severity of adverse events (AEs) and adverse events of special interest (AESIs), the incidence of serious adverse events (SAEs), and changes in laboratory test results, vital signs, and ECG results. Secondary endpoints include the proportion of CRESS responders on at least 3 of 5 items at weeks 24 and 48, and the proportion of participants with minimal clinically important improvement from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and the clinical ESSDAI (clinESSDAI), with improvements defined as a decrease of at least 3 points at weeks 24 and 48.

Additional secondary endpoints involve the proportion of participants achieving low disease activity, defined as an ESSDAI or clinESSDAI score of less than 5 at weeks 24 and 48, and the proportion of participants with minimal clinically important improvement in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), defined as a decrease of at least 1 point or 15% at weeks 24 and 48. Changes from baseline in ESSDAI, clinESSDAI, and ESSPRI scores at weeks 24 and 48 will also be evaluated. The proportion of STAR responders, defined as a score of at least 5, will be assessed at weeks 24 and 48 compared to baseline.

Biomarker assessments include values, changes from baseline, and percent reduction from baseline in total IgG levels and autoantibodies (Anti-Ro/SS A and Anti-La/SS B) in serum over the 48-week treatment period. Efgartigimod serum concentrations and the incidence and prevalence of anti-drug antibodies (ADA) against efgartigimod will be monitored throughout the 48-week treatment period. These efficacy parameters will be measured and collected at specified timepoints, including weeks 24 and 48, using validated scales and laboratory tests to ensure accurate and reliable data collection and analysis.