This phase 1b, multicenter, double-blinded, placebo-controlled study (NCT06436742) evaluated safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of ARGX-119 in adults with DOK7 congenital myasthenic syndromes (DOK7-CMS).

CMS are a rare, heterogeneous group of inherited disorders caused by mutations impairing neuromuscular transmission, with no approved treatments. Mutations in the DOK7 gene represent one of the common causes of CMS. ARGX-119, a humanized, agonistic, monoclonal antibody, specifically targets and activates muscle-specific kinase, which may stabilize and improve neuromuscular junction function in DOK7-CMS, to potentially reduce muscle weakness/fatigability and improve quality of life (QoL).

Participants underwent intrapatient dose escalation and were randomized 4:1 to intravenous ARGX-119 or placebo for 6 doses over the 12-week treatment period followed by a ~7-month follow-up period. Primary endpoint was safety assessment. Efficacy endpoints included key components of the Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Activities of Daily Living (MG-ADL) score, and PROMIS Global Health score, measures of physical function and mobility (eg, Six-Minute Walk Test [6MWT] total distance walked and cadence assessed using digital sensors), and QoL.

Sixteen participants were randomized to ARGX-119 (n=13) or placebo (n=3). ARGX-119 was well tolerated, with no serious adverse events (AEs), grade ≥3 AEs, or discontinuations due to AEs. Clinically meaningful increase (≥50 m) in median 6MWT distance was reported in participants receiving ARGX-119, with consistent improvements in median cadence measured using digital sensors. Improvements occurred in QMG key components (“both legs outstretched,” “both arms outstretched,” and “head lifted”) in the ARGX-119 arm. Consistent improvements also occurred in MG-ADL over time compared with study baseline in the ARGX-119 arm. Ambulatory (no wheelchair use at baseline) participants receiving ARGX-119 demonstrated coherence in response across most endpoints measuring leg function; this coherence in response did not occur in participants in the placebo arm.

Results demonstrate proof-of-biology for ARGX-119 in participants with DOK7-CMS.