Design and Status Update on the SYNAPSE-SMA Phase 2, Trial of NMD670 in Ambulatory Adults with Spinal Muscular Atrophy Type 3


Clinical Trials

Poster Number: S114


Vera Kiyasova, MD, PhD, NMD Pharma A/S, Thomas Thomas Skjærlund Grønnebæk, MSc, PhD, NMD Pharma A/S, Caitlin Cornwall, NMD Pharma A/S, Jitendra Gupte, NMD Pharma A/S, Claire Sampson, PhD, NMD Pharma A/S, Teresa Gidaro, MD, PhD, NMD Pharma A/S, Thomas Holm Pedersen, PhD, NMD Pharma A/S, Jorge Quiroz, MD, MBA, NMD Pharma A/S

Despite recent breakthroughs in the treatment of spinal muscular atrophy (SMA), preclinical and clinical studies indicate that in addition to motor neuron degeneration, the transmission of signals from nerve to muscle is dysfunctional in SMA and that this transmission deficit may persist despite treatment with currently available therapies. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for the treatment of SMA. NMD670 is a novel first-in-class neuromuscular transmission enhancer working through selective inhibition of the skeletal muscle chloride channel 1 (ClC-1) that is being developed by NMD Pharma for the treatment of neuromuscular disorders characterized by neuromuscular transmission dysfunction.
The SYNAPSE-SMA study is a proof-of-concept, phase 2, randomized, double-blind, placebo-controlled, 2-way crossover study to evaluate the efficacy, safety, and tolerability of NMD670 in ambulatory adults with type 3 SMA. An estimated 54 ambulatory adults with type 3 SMA will be randomized at approximately 25 sites in North America and Europe. Eligible participants will be randomized to receive NMD670 or placebo twice daily for 21 days and will cross over to the opposite treatment after a 7-day washout period. The primary endpoint is the change from baseline versus placebo in total distance walked during the 6-minute walk test. Secondary endpoints include safety and tolerability, and the change from baseline versus placebo in muscle strength (handheld dynamometry), motor function (Revised Hammersmith Scale), fatigue (endurance shuttle nine-hole peg test and fatigue index calculated from 6-minute walk test) and neuromuscular transmission (single fiber electromyography). Exploratory outcomes include pharmacokinetics and change from baseline versus placebo in patient reported fatigue (Fatigue Severity Scale) and quality of life (Individual Neuromuscular Quality of Life Scale).
The first subject was enrolled in September 2023 and NMD Pharma will provide a status update on enrolment during the Muscular Dystrophy Association Clinical and Scientific Conference in Orlando, March 2024