Phase 2a Study to Evaluate the Safety and Efficacy of Empasiprubart as Add-on Therapy to Efgartigimod in Participants With AChR-Ab Seropositive Generalized Myasthenia Gravis

The primary objective is to determine the safety and tolerability of empasiprubart as an add-on therapy to efgartigimod in participants with AChR-Ab seropositive generalized myasthenia gravis who exhibit a partial clinical response to efgartigimod. Secondary objectives include:

• Evaluation of the efficacy of multiple regimens, including monotherapy or add-on therapy to backbone therapy, in various subtypes of myasthenia gravis.
• Comparison of the efficacy of empasiprubart as an add-on therapy to efgartigimod versus efgartigimod alone.

This clinical trial involves 18 participants diagnosed with generalized Myasthenia Gravis. The study population consists of both male and female patients who are AChR-Ab seropositive. Eligible individuals must meet specific Myasthenia Gravis Foundation of America classification criteria, specifically classes II, III, IVa, or IVb. Participants must be at least 18 years of age and maintain a stable dosage of any current immunosuppressive drugs, corticosteroids, or acetylcholinesterase inhibitors prior to screening. Additionally, subjects must have documented immunization against Neisseria meningitidis and Streptococcus pneumoniae within the previous five years or be willing to undergo vaccination before the initial administration of the study drug.

This Phase 2a, proof-of-concept platform study is designed to evaluate the safety, tolerability, and efficacy of various regimens in participants with generalized myasthenia gravis. The specific investigation evaluates empasiprubart administered via IV infusion as an add-on therapy to efgartigimod alfa for individuals who are AChR-Ab seropositive and have demonstrated a partial clinical response to efgartigimod. The research methodology involves a master protocol approach to assess multiple regimens. The study sequence begins with a screening visit to confirm eligibility based on MGFA classification and immunization status against encapsulated bacterial pathogens. Following screening, participants undergo treatment and subsequent follow-up assessments to monitor adverse events, vital signs, ECG, and laboratory parameters. Secondary objectives include measuring changes in disease severity using the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score and the Quantitative Myasthenia Gravis (QMG) total score. The trial is estimated to occur between March 2026 and March 2028.

Empasiprubart is an investigational medicinal product administered as a concentrate for solution for infusion via intravenous infusion. This substance is evaluated for use as add-on therapy in participants with AChR-Ab seropositive generalized myasthenia gravis.

Efgartigimod alfa is an orphan drug provided as a solution for infusion for intravenous infusion. The administered dose is 1200 mg, serving as the backbone therapy in the study regimen.

Efficacy assessment in this study of myasthenia gravis involves several clinical measures. The primary evaluation of disease severity is based on changes in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score and the Myasthenia Gravis Impairment Index (MGII) total score from baseline. Additional assessments include the Quantitative Myasthenia Gravis (QMG) total score to evaluate clinical changes.

The study monitors the proportion of participants achieving minimal symptom expression (MSE) at various time points. Secondary measures also include the frequency of a 50% improvement in the MG-ADL total score and the attainment of a patient acceptable symptom state (PASS). For specific study parts, MG-ADL and QMG total scores, including actual values and changes from baseline, are measured at week 4 and week 18 to allow for comparative analysis across different treatment cycles.