Phase 2a Randomized Double‑Blind Placebo‑Controlled Study of Empasiprubart IV Monotherapy in AChR‑Ab Seropositive Generalized Myasthenia Gravis

The primary objective is to determine the safety and tolerability of multiple treatment regimens—either as monotherapy or as add‑on to backbone therapy—in participants with acetylcholine‑receptor antibody seropositive generalized Myasthenia Gravis, establishing an acceptable risk profile for further therapeutic development. Secondary objectives include evaluation of the efficacy of the various regimens across Myasthenia Gravis subtypes and assessment of the efficacy of empasiprubart IV compared with placebo, providing data on clinical benefit relative to standard care.

The trial enrolled 11 participants diagnosed with Myasthenia Gravis, all of whom were ≥ 18 years old; the age range encompassed adult patients as defined by the study’s inclusion criteria. Both female and male individuals were represented, and the population included participants classified as vulnerable. Eligibility required a confirmed diagnosis of generalized disease with seropositivity for anti‑acetylcholine receptor antibodies, corresponding to Myasthenia Gravis Foundation of America (MGFA) classes II–IVb, and a stable regimen of existing MG therapies (including non‑steroidal immunosuppressive drugs, corticosteroids, or acetylcholinesterase inhibitors) prior to screening. Participants also needed documented immunization against encapsulated bacterial pathogens within the preceding five years or completion of such immunization at least 14 days before study drug administration. No additional lifestyle or habit‑related criteria were specified.

The study is an exploratory Phase 2a, randomized, double‑blind, placebo‑controlled trial evaluating the safety, tolerability and efficacy of intravenous empasiprubart monotherapy in participants with AChR‑Ab seropositive generalized Myasthenia Gravis. Eligible adults (≥18 years) with confirmed diagnosis and stable background therapy undergo a screening visit to verify inclusion criteria, including documented immunization against encapsulated bacteria. Following randomization, participants receive study drug or matching placebo by IV infusion and attend scheduled follow‑up visits at weeks 4, 8 and 12 for safety assessments, vital signs, ECG, laboratory tests and efficacy evaluations (MG‑ADL, QMG). The end‑of‑study visit at week 12 concludes the 12‑week treatment period; total participant involvement, including screening, is approximately 14 weeks. Early termination may be initiated for emergent serious adverse events, clinically significant laboratory abnormalities, or failure to adhere to protocol requirements. The overall recruitment period is planned from August 2026 to January 2028.

The investigational product Vyvgart 1 000 mg solution for injection in a pre‑filled syringe contains the active substance efgartigimod alfa. It is supplied as a sterile solution for injection and is administered by subcutaneous injection at a dose of 1000 mg per administration. The dosing frequency follows the protocol‑specified schedule, and each administration is documented in the participant’s dosing log to ensure compliance.

The test agent ARGX‑117, identified as empasiprubart, is provided as a concentrate for solution for infusion. It is delivered by intravenous infusion with a weight‑based dosing specification expressed in milligrams per kilogram. Infusions are performed according to the study‑defined schedule, and infusion parameters, including start and end times, are recorded in the infusion record to monitor adherence.

The placebo comparator is formulated to match the appearance of the empasiprubart IV preparation. It is administered by intravenous infusion on the same schedule as the active investigational product, with identical procedural documentation to maintain blinding and to track participant compliance.

Efficacy will be evaluated using changes from baseline in disease‑specific severity scores, including the Myasthenia Gravis Activities of Daily Living (MG‑ADL) total score, the Myasthenia Gravis Impairment Index (MGII) total score, and the Quantitative Myasthenia Gravis (QMG) total score. Additional efficacy measures comprise the proportion of participants achieving minimal symptom expression (MSE), a ≥3‑point reduction in MG‑ADL, a ≥5‑point reduction in QMG, a positive Patient Acceptable Symptom State (PASS), and a ≥50 % improvement in the MG‑ADL total score.

These parameters will be collected using the respective validated scales at baseline and at scheduled visits through week 12, with interim values recorded up to the end of the double‑blind treatment period. Changes from baseline will be calculated for each time point, and categorical outcomes (e.g., proportion attaining MSE or predefined score reductions) will be summarized. Statistical analyses will compare the active treatment group with placebo for each efficacy endpoint, employing appropriate methods for continuous and binary outcomes.