Overview
This study aims to find the correct dose of ARGX-119 for children with SMA. The study will also look at how safe the study drug is, how well it works, how it moves through the body, and how the immune system responds to it. The study consists of a double-blinded treatment period (DBTP) where participants will either receive ARGX-119 IV or placebo IV, in addition to disease-modifying therapy (DMT) for 24 weeks. Participants who complete the DBTP will enter the open-label active-treatment extension period (ATEP) during which all participants will receive ARGX-119 IV up to 100 weeks (approximately 2 years).
Description
This phase 2 study aims to establish proof of concept with the age-appropriate dose of ARGX-119 in ambulant pediatric patients with spinal muscular atrophy (SMA). Despite available treatments, there remains an unmet medical need for patients with SMA. Neuromuscular junction (NMJ) dysfunction contributes to the pathophysiology of SMA, including muscle weakness and fatigability. Activation of muscle-specific kinase (MuSK) by ARGX-119 may stabilize and improve NMJ function in patients with SMA, reducing muscle weakness and fatigability, and improving quality of life.
Eligibility
Inclusion Criteria:
- Is aged ≥5 to \<18 years when completing the informed consent process, defined as providing informed assent according to local regulations and having a parent or guardian sign the ICF, and can comply with protocol
- requirements.
- Has documented historical genetic diagnosis of 5q-SMA.
- Currently receiving a stable SMA treatment regimen (nusinersen or risdiplam) and/or have a history of onasemnogene abeparvovec treatment
- Must be able to walk at least 50 meters without walking aids in the 6MWT at screening
Exclusion Criteria:
- Known medical condition that would interfere with an accurate assessment of SMA, confound the results of the study, or put the participant at undue risk, as assessed by the investigator
- Recent major surgery, except spinal fusion, within 3 months of screening or intends to have major surgery during the study
- Current or previous administration of antimyostatin therapies in the past 6 months
- Severe scoliosis (defined as curvature \>40°) and/or contractures at screening. o History of spinal fusion within 6 months before screening or planned during the study
- Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for daytime treatment while awake. Ventilation used overnight or during daytime naps is acceptable.