Phase 3B Randomized Study on Efgartigimod Alfa IV Dosing Regimens in Generalized Myasthenia Gravis Patients

The primary objective of this study is to assess the **clinical efficacy** of efgartigimod IV 10 mg/kg administered in a q2w continuous regimen compared to a cyclic regimen in patients with Generalized Myasthenia Gravis (gMG). This evaluation is clinically relevant as it aims to determine the optimal dosing strategy to maximize and maintain clinical benefit in managing gMG, a chronic autoimmune neuromuscular disorder characterized by weakness and fatigue of voluntary muscles.

Secondary objectives include:

• Evaluating the **safety** and tolerability of both treatment regimens throughout the study, which is crucial for ensuring patient safety and identifying any adverse effects associated with the treatment.
• Assessing the clinical efficacy of efgartigimod IV in both treatment regimens over time, providing insights into the long-term benefits and effectiveness of the treatment.
• Comparing the number of participants who achieve maximal clinical effect during different treatment regimens, which will help in understanding the comparative effectiveness of the dosing strategies.

The clinical trial involves a total of **26 participants** diagnosed with **Generalized Myasthenia Gravis (gMG)**. The study population includes both male and female subjects, aged 18 years and older, who are in general good health aside from their condition. Participants were selected based on their ability to provide informed consent and meet specific clinical criteria, including a confirmed diagnosis of gMG and a Myasthenia Gravis – Activities of Daily Living (MG-ADL) total score of 5 or higher, with more than 50% of the score attributed to nonocular symptoms. The trial does not include a vulnerable population. Participants are permitted to continue their existing gMG treatments, such as nonsteroidal immunosuppressive drugs, steroids, and acetylcholinesterase inhibitors, provided these treatments have been stable for at least one month prior to the study. Lifestyle considerations, such as the use of contraceptive measures, are required in accordance with local regulations, particularly for women of childbearing potential, who must also have negative pregnancy tests before receiving the study drug.

The clinical trial is a **Phase 3B**, randomized, open-label, parallel-group study designed to evaluate different dosing regimens of intravenous **efgartigimod alfa** in patients with **Generalized Myasthenia Gravis (gMG)**. The primary objective is to assess the clinical efficacy of efgartigimod IV 10 mg/kg administered in a q2w continuous regimen compared to a cyclic regimen. The trial is expected to conclude by May 31, 2026, with recruitment having commenced on October 25, 2021. Participants will be involved in the study for a maximum treatment period of 126 days.

The trial includes several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the screening visit, eligibility is confirmed based on criteria such as age, diagnosis of gMG, and seropositivity for anti-acetylcholine receptor antibodies. Follow-up visits occur at specified intervals to monitor the **Myasthenia Gravis – Activities of Daily Living (MG-ADL)** total score and assess any adverse events. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted.

Participants may be withdrawn from the study if they experience severe adverse events, fail to comply with the protocol, or choose to withdraw consent. The primary endpoint is the mean change in the MG-ADL total score from baseline during weeks 1 through 21. Secondary endpoints include the incidence and severity of adverse events, changes in laboratory test results, and the percentage of participants achieving minimal symptom expression. The study aims to provide valuable insights into optimizing treatment regimens for gMG, with a focus on maximizing and maintaining clinical benefits.

The clinical trial involves the administration of **Vyvgart**, a **20 mg/mL concentrate for solution for infusion**. The active substance in this experimental medication is **efgartigimod alfa**, a protein-based therapeutic agent. Vyvgart is formulated as a **sterile concentrate** and is intended for **intravenous use**. The dosing regimen for this trial includes a maximum daily dose of **1200 mg** and a total maximum dose of **80400 mg** over a treatment period of up to **126 days**. The administration schedule is designed to evaluate different dosing regimens, specifically comparing a continuous regimen of **10 mg/kg every two weeks (q2w)** with a cyclic regimen, to optimize and maintain clinical benefits in patients with **generalized myasthenia gravis**.

In addition to the experimental treatment, the study may include the use of standard-of-care therapies as deemed necessary by the clinical investigators. These non-experimental treatments are not specified in the trial data but are typically used to manage symptoms or provide supportive care to participants. The trial does not include a placebo or comparator treatment group, focusing solely on the efficacy of the experimental medication. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol and to accurately assess the treatment's efficacy and safety.

The clinical trial aims to assess the efficacy of intravenous **efgartigimod alfa** in patients with Generalized Myasthenia Gravis (gMG). The primary endpoint for evaluating efficacy is the mean change in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score from baseline during the visits from week 1 through week 21, analyzed by regimen arm. Secondary endpoints include the incidence and severity of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and changes in laboratory test results, vital sign measurements, and electrocardiogram results. Additionally, the change from baseline in the MG-ADL total score over time will be assessed, along with the normalized area under the effect curve (AUEC) of MG-ADL total score improvement from baseline during specified intervals. The characterization of MG-ADL total score change from baseline will be evaluated using mean and standard deviation across several intervals, and the number and percentage of participants achieving specific improvements in MG-ADL total score will be recorded. The percentage of time participants experience a reduction in MG-ADL total score of at least 2 points from baseline during weeks 4 through 21 will also be measured. Furthermore, the number and percentage of participants achieving minimal symptom expression (MSE), defined as an MG-ADL total score of 0 or 1, will be determined across various intervals.