LB: Efficacy and safety of ignaseclant in adults with Charcot-Marie-Tooth Disease: Top Line Results of a Phase 2a study.

Topic:

Clinical Trials

Poster Number: 471 LBT

Author(s):

W. David Arnold, MD, University of Missouri - Columbia, David Herrmann, MBBCh, University of Rochester. Medical Centre Neurology, Kristl G. Claeys, Department of Neurology, University Hospitals Leuven, Belgium, Henning Andersen, MD, PhD, Dept of Neurology. Aarhus University Hospital, Gregory Carter, St Lukes Rehabilitation Medical Center, Spokane WA, Yessar Hussein, Austin Neuromuscular Center, Thomas S. Grønnebæk, PhD, NMD Pharma A/S, Thomas Breuer, MSc, NMD Pharma A/S, Teresa Gidaro, MD, PhD, NMD Pharma A/S, Thomas Holm Pedersen, PhD, NMD Pharma A/S, Ana de Vera, MD, NMD Pharma A/S

Background
Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy characterized by progressive skeletal muscle weakness and functional impairment, with no approved pharmacologic therapies. Ignaseclant (formerly NMD670) is a first-in-class, inhibitor of the skeletal muscle chloride channel ClC-1, developed to enhance muscle activation in response to nerve signaling through the neuromuscular junction (NMJ).
Methods
SYNAPSE-CMT (NCT06482437) was a randomized, double-blind, placebo-controlled Phase 2a trial evaluating ignaseclant administered twice daily in adults with genetically confirmed type 1 or type 2 CMT. 80 participants received ignaseclant or placebo for 21 days, with follow up at Day 28. The primary endpoint was change from baseline in the 6-minute walk test (6MWT). Secondary endpoints included the Charcot-Marie-Tooth Functional Outcome Measure (CMT-FOM), its individual functional components, and the Charcot-Marie-Tooth Health Index (CMT-HI).
Results
No treatment effect was observed in the 6MWT. Numerical improvement versus placebo was observed in the CMT-FOM total score at 21 days and was sustained at Day 28, (p=0.06 vs placebo). Hand grip strength increased after 7 days and reached statistical significance at Day 21 (p=0.02 vs placebo) and at Day 28 (p<0.01 vs placebo). Improvement was also observed in the 9-hole peg test. Numerical improvement was observed in the patient-reported CMT-HI mean total score with a higher proportion of responders (>3.2 points) at day 21 with ignaseclant (53.2%) versus placebo (36.8%). All adverse events were mild or moderate and did not lead to treatment discontinuation. No serious adverse events were reported with ignaseclant.
Conclusions
SYNAPSE-CMT topline results show that ClC-1 inhibition with ignaseclant over 21 days is associated with improvements in muscle strength and motor function in adults with CMT, persisting 7 days after treatment discontinuation, suggesting structural recovery at the NMJ. These findings were supported by patients’ perception. Full results will be presented at an upcoming scientific meeting.