Evaluation of Long-term Safety of Intravenous and Subcutaneous Efgartigimod Alfa in Pediatric Patients with Generalized Myasthenia Gravis

The primary objective of this study is to evaluate the **safety** and **tolerability** of efgartigimod administered intravenously (IV) and efgartigimod PH20 administered subcutaneously (SC) in children with Generalized Myasthenia Gravis. This is clinically relevant as it aims to ensure that the treatment is safe for pediatric patients, which is crucial for the management of this chronic autoimmune neuromuscular disorder.

Secondary objectives include:

• To evaluate the **immunogenicity** of efgartigimod IV and efgartigimod PH20 SC. Assessing immunogenicity is important to understand the potential for immune response against the therapeutic agent, which could impact its efficacy and safety.

The clinical trial involves a total of **13 participants** diagnosed with **Generalized Myasthenia Gravis**. The study population includes both male and female subjects, with an age range that falls within the category code "2," indicating a specific age group as defined by the trial's criteria. Participants were selected based on their completion of previous studies, ARGX-113-2006 or ARGX-113-2207, and their agreement to participate in the current study, ARGX-113-2008. The trial includes a vulnerable population, suggesting that special considerations are in place to ensure their safety and compliance with the study protocol. Participants are required to understand the study requirements and provide informed consent, with contraceptive use being consistent with local regulations for those of childbearing potential. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **safety** and tolerability of **efgartigimod** administered both intravenously and subcutaneously in children diagnosed with **generalized myasthenia gravis**. This is a long-term, single-arm, open-label, multicenter study. The trial is expected to span from August 2022 to September 2028, with a maximum treatment period of 24 months for each participant. The study involves the administration of Vyvgart, available as a 1,000 mg solution for injection and a 20 mg/mL concentrate for solution for infusion, both containing the active substance **efgartigimod alfa**.

Participants eligible for this trial must have completed previous studies ARGX-113-2006 or ARGX-113-2207 and must provide informed consent. The primary endpoints focus on the incidence and severity of adverse events, serious adverse events, and adverse events of special interest, along with changes in laboratory test results, vital signs, height, weight, and electrocardiogram results. Secondary endpoints include the incidence and prevalence of antidrug antibodies against efgartigimod and antibodies against recombinant human hyaluronidase PH20.

The trial involves several study visits, beginning with a screening visit to confirm eligibility. Participants will undergo regular follow-up visits to monitor safety and efficacy, with assessments including laboratory tests and physical examinations. The end-of-study visit will conclude the participant's involvement, ensuring all safety parameters are reviewed. The expected length of participant involvement is up to 24 months, with conditions for early termination including withdrawal of consent, non-compliance with the study protocol, or adverse events that necessitate discontinuation.

The clinical trial involves the administration of **efgartigimod alfa**, a biological medicinal product, in two distinct pharmaceutical forms. The first form is **Vyvgart 1,000 mg solution for injection**, which is administered via **subcutaneous injection**. This formulation is provided as a solution for injection, with a maximum daily dose of 1,000 mg and a total maximum dose of 104,000 mg over a treatment period of up to 24 weeks. The active substance, efgartigimod alfa, is a protein of non-chemical origin, specifically a human monoclonal antibody fragment targeting the FcRn receptor. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.

The second form of efgartigimod alfa used in the trial is **Vyvgart 20 mg/mL concentrate for solution for infusion**, administered through **intravenous infusion**. This formulation is a sterile concentrate that requires dilution before administration. The maximum daily dose for this form is 1,200 mg, with a total maximum dose of 124,800 mg over the same 24-week treatment period. As with the subcutaneous form, the intravenous administration is closely monitored to ensure proper dosing and participant compliance. Both forms of efgartigimod alfa are produced by ARGENX BV and are designated as orphan drugs, highlighting their use in treating rare conditions such as **generalized myasthenia gravis**.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the safety profile of **efgartigimod** when administered intravenously and subcutaneously. These include the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Additionally, changes in laboratory test results, vital signs, height and weight, and electrocardiogram (ECG) results will be monitored to evaluate the safety and tolerability of the treatment.

Secondary endpoints will assess the immunogenicity of the treatment by measuring the incidence and prevalence of antidrug antibodies (ADAs) against **efgartigimod** and antibodies against recombinant human hyaluronidase PH20 (rHuPH20). These parameters will be collected and analyzed throughout the trial to provide comprehensive data on the treatment's safety and potential immunogenic response in participants.