Design of a Phase 2, Double-Blind, Placebo-Controlled Study of Adimanebart (ARGX-119) IV in Pediatric Participants With SMA: SPARKLE

Topic:

Clinical Trials

Poster Number: 93 S

Author(s):

Guinevere Valencia, argenx, John Brandsema, MD, Children's Hospital of Philadelphia, Karolien Van Huynegem, PhD, argenx, Ghent, Belgium, Laurent Servais, MD PhD, University of Oxford, John Day, MD, PhD, Stanford, Tonke van Bragt, MSc, argenx, Ghent, Belgium, Roeland Vanhauwaert, PhD, argenx, Ghent, Belgium, Rivka Noelanders, PhD, argenx, Ghent, Belgium, Elisabeth Coart, PhD, argenx, Ghent, Belgium, Flavia Menezes, MD, argenx, Ghent, Belgium, Jacqueline Montes, PT, EdD, Columbia University Irving Medical Center, New York, NY, US

Despite available treatments, a significant unmet need remains in spinal muscular atrophy (SMA). Neuromuscular junction (NMJ) dysfunction may contribute to SMA pathophysiology, therefore, stabilizing the NMJ offers an approach that complements disease-modifying therapies (DMTs). Adimanebart (ARGX-119) is a humanized, agonistic, monoclonal antibody that specifically targets and activates muscle-specific kinase (MuSK) at the NMJ, promoting MuSK dimerization, phosphorylation, and activation, to stabilize the NMJ. In vitro and in vivo nonclinical pharmacology studies demonstrated the MOA of adimanebart at the NMJ. By improving NMJ function, adimanebart might significantly benefit individuals with SMA.
SPARKLE (NCT07287982) is a phase 2, double-blind, randomized, placebo-controlled study in pediatric participants with SMA. The study aims to establish proof of concept of age-appropriate doses and evaluate safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of intravenous (IV) adimanebart. Eligible participants will be 5–17 years old, with confirmed genetic diagnosis of 5q-SMA, and concomitant DMT. At screening, participants must walk ≥50 m unaided in the Six-Minute Walk Test (6MWT) and have a Revised Hammersmith Scale (RHS) score >15 and <50. Approximately 60 participants will be randomized 1:1:1 to receive age-appropriate low- or high-dose adimanebart IV or placebo IV (double-blind treatment period [DBTP; 24 weeks], dosing: Days 1, 15, and 29, then every 4 weeks [Q4W]). Treatment will be in addition to DMT. Participants completing the 24-week double-blind treatment period (DBTP) may enter the open-label, 2-year active treatment extension period of high-dose adimanebart IV Q4W. A safety follow-up of 20 weeks will follow the final dose. Primary endpoint: change in RHS total score from baseline to DBTP Week 24. Secondary endpoints: 6MWT distance; fatigability, assessed via performance metrics during the 6MWT and perceived fatigability using the SMA EFFORT measure; PK; and immunogenicity. A digital wrist device will monitor real-world physical activity. Interim analysis will occur when all participants complete DBTP Week 12. Acknowledgments: This study is sponsored by argenx. Medical writing support was provided by Envision Ignite, an Envision Medical Communications agency, a part of Envision Pharma Group, funded by argenx.