Efficacy and Safety Evaluation of Efgartigimod Alfa in Adults with Ocular Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

The primary objective of this study is to determine the **efficacy** of efgartigimod PH20 SC compared to placebo PH20 SC in participants with **ocular myasthenia gravis** (oMG) in part A. This is clinically relevant as it aims to establish the therapeutic potential of efgartigimod PH20 SC in managing symptoms of oMG, a condition characterized by muscle weakness affecting the eyes, which can significantly impact patients' quality of life.

Secondary objectives include:

• To determine the efficacy of efgartigimod PH20 SC compared to placebo and the long-term efficacy of efgartigimod PH20 SC in participants with oMG.
• To assess the safety and tolerability of efgartigimod PH20 SC compared to placebo and the long-term safety and tolerability of efgartigimod PH20 SC in participants with oMG.
• To evaluate the impact of efgartigimod PH20 SC on Quality of Life in participants with oMG.
• To assess the pharmacodynamics effect of efgartigimod PH20 SC in participants with oMG.
• To assess the immunogenicity of efgartigimod PH20 SC in participants with oMG.

The clinical trial involves a total of **98 participants** diagnosed with **Ocular Myasthenia Gravis**. The study population includes both male and female subjects, aged 18 years and older, who meet the local legal age of consent for clinical studies. Participants were selected based on a confirmed diagnosis of myasthenia gravis, supported by seropositivity for AChR-Ab or abnormal neuromuscular transmission, and a history of positive edrophonium chloride testing or demonstrated improvement on MG therapy. All participants are classified as MGFA Class I, indicating any ocular muscle weakness, and have a screening and baseline MGII (PRO) ocular score of at least 6, with at least 2 ocular items scoring at least 2. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, Phase 3 study to evaluate the efficacy and safety of **efgartigimod** PH20 SC in adult participants diagnosed with **ocular myasthenia gravis**. The trial will involve a parallel-group design, with participants receiving either the investigational product or a placebo. The study is expected to commence recruitment on February 15, 2025, and conclude by April 30, 2028, with a maximum treatment period of 119 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and specific **myasthenia gravis** classification. The primary endpoint is the change in the MGII (PRO) ocular score from baseline to day 29. Secondary endpoints include various ocular and total score changes, incidence and severity of adverse events, and changes in laboratory parameters. Follow-up visits will be scheduled to monitor these endpoints and ensure participant safety. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

Participant involvement is expected to last for the duration of the treatment period, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or non-compliance with study protocols. The investigational product, **efgartigimod**, is administered via subcutaneous injection using a pre-filled syringe, with a maximum daily dose of 1000 mg and a total dose not exceeding 110,000 mg over the treatment period. The study aims to provide comprehensive data on the efficacy and safety of **efgartigimod** in treating **ocular myasthenia gravis**.

The clinical trial involves the administration of **Efgartigimod**, an experimental medication, to evaluate its efficacy and safety in adult participants with **ocular myasthenia gravis**. Efgartigimod is provided as a **solution for injection in a pre-filled syringe**. The active substance in this medication is **efgartigimod alfa**, a protein of the category "Protein - Other". The pharmaceutical form is specifically designed for **subcutaneous injection**. The maximum daily dose of Efgartigimod is 1000 mg, with a total maximum dose of 110,000 mg over the treatment period. The treatment duration is set for a maximum of 119 days. The administration schedule and participant compliance are monitored throughout the trial to ensure adherence to the dosing regimen.

The study also includes a **placebo** group, where participants receive a placebo treatment, referred to as Placebo PH20 SC. The placebo is used as a comparator to assess the efficacy of Efgartigimod. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the true effect of the experimental medication.

The efficacy of **efgartigimod** PH20 SC in the treatment of ocular myasthenia gravis will be assessed through a randomized, double-blinded, placebo-controlled, Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the change in the MGII (PRO) ocular score from baseline to day 29 in part A of the study. Secondary endpoints include changes in the MGII (PRO+PE) ocular score, MG-ADL ocular domain score, MGII total score, and MGII (PE) ocular score from baseline to day 29 in part A. Additionally, the study will assess the MG-ADL total score, MGII ocular scores (PRO, PRO+PE, and PE), generalized score, and total score, as well as the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) in both part A and part A+B.

Further secondary endpoints involve clinically relevant changes in laboratory parameters, vital signs, and ECGs, as well as the MG-QoL15r total score and NEI VFQ-25 score, with actual values and changes from baseline being measured. The study will also monitor actual values and percent changes from baseline in total IgG levels and AChR-Ab levels in AChR-Ab seropositive participants over time. The incidence and prevalence of Anti-Drug Antibodies and Neutralizing Antibodies against efgartigimod and rHuPH20 will also be evaluated. These efficacy parameters will be collected and analyzed at specified timepoints, including baseline and day 29, using validated scales and laboratory tests to ensure accurate and reliable data collection.