Safety, Efficacy, And Pharmacokinetics of Argx-117 in Adults With Multifocal Motor Neuropathy: A Global, Multicenter, Placebo Controlled Phase 2 Study (Arda)

Objective To report the study design of a Phase 2, multicenter, randomized, placebo controlled, parallel-group study (ARDA, NCT05225675) will assess the safety, efficacy, PK, and PD of ARGX-117 in adults with MMN. Background Multifocal motor neuropathy (MMN) is a chronic, immune-mediated neuropathy characterized by progressive asymmetric weakness predominantly affecting the distal upper limbs. MMN is often associated with anti-GM1 IgM antibodies targeting the axolemma at the node of Ranvier, leading to activation of the classical complement pathway which drives subsequent damage to the axon. IVIg is the only proven effective therapy. ARGX-117 is a novel monoclonal antibody that inhibits complement factor 2 (C2). Using an in vitro model for MMN, ARGX-117 was shown to block IgM-mediated classical pathway complement activation on both motor neurons and Schwann cells. ARGX-117 is being studied in adults with MMN in a Phase 2, multicenter, randomized, placebo controlled, parallel-group study. Design/Methods Forty-eight participants will be recruited and assigned to one of two dosing cohorts (24 participants each) and randomized 2:1 within each cohort to receive either ARGX-117 or placebo. Key inclusion criteria include: diagnosis of probable or definite MMN per 2010 EFNS/PNS guidelines, stable IVIg regimen, and IVIg treatment dependency. The primary objective is safety based on adverse event monitoring and other safety assessments. Secondary objectives include assessment of efficacy measured as strength and functional disability, pharmacokinetics, pharmacodynamics (C2 and CH50), and immunogenicity of ARGX-117. After completing the 16-week treatment period, participants may enroll in an open-label extension study, or enter the safety follow-up period. Results This ongoing phase 2 study will assess the safety and efficacy of ARGX-117 in participants with MMN. Conclusions The results of this study will inform and direct future studies of ARGX-117 in this patient population.