Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene, leading to loss of functional dystrophin protein. Exon skipping therapies aim to restore the dystrophin reading frame by modifying pre-mRNA splicing, enabling production of internally truncated but functional dystrophin. Approximately 4% of individuals with DMD are amenable to exon 50 skipping. NS 050/NCNP 03 is an antisense oligonucleotide designed for patients with mutations suitable for exon 50 skipping. This abstract summarizes the design of a first-in-human Phase 1/2 study evaluating NS 050/NCNP 03 in ambulatory boys with DMD.
Methods: This multicenter Phase 1/2 study (NCT06053814) will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of NS 050/NCNP 03. Eligible participants are males aged ≥4 to <15 years with a confirmed DMD gene mutation amenable to exon 50 skipping. Part 1 is a randomized, double blind, placebo-controlled dose escalation phase in which nine participants will receive once weekly intravenous NS 050/NCNP 03 or placebo for two weeks at each dose level. Primary endpoints include safety, tolerability, and pharmacokinetics. Part 2 will enroll an additional 11 participants (total N = 20), all receiving the maximum tolerated dose identified in Part 1 once weekly for 24 weeks. The primary endpoint for Part 2 is dystrophin protein expression in skeletal muscle after 24 weeks. Secondary endpoints include safety, tolerability, dystrophin mRNA induction, and changes in strength and functional mobility compared with a group-matched natural history cohort. Conclusion: This Phase 1/2 trial is the first clinical evaluation of NS 050/NCNP 03 and is designed to characterize safety, pharmacokinetics, pharmacodynamics, and early efficacy signals to support further development.