A Phase 1/2 study of NS-050/NCNP-03, an investigational exon 50 skipping therapy, in boys with Duchenne muscular dystrophy (Meteor50): Trial design


Clinical Trials

Poster Number: M160


Vamshi K. Rao, MD, Division of Neurology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA, Erika Finanger, MD, Oregon Health & Science University, Michelle L. Previtera, PhD, NS Pharma, Inc., Paramus, NJ, USA, Robert A. Crozier, PhD, NS Pharma, Inc., Paramus, NJ, USA, Leslie Magnus, MD, NS Pharma, Inc., Paramus, NJ, USA, Eric Hoffman, PhD, AGADA Biosciences, Inc., Hirofumi Komaki, MD, PhD, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan, Yoshitsugu Aoki, MD, PhD, National Center of Neurology and Psychiatry (NCNP), Paula Clemens, MD, University of Pittsburgh

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by dystrophin gene mutations, resulting in loss of functional dystrophin protein. Exon-skipping strategies may reduce symptoms and improve quality of life by altering dystrophin pre-messenger RNA (mRNA) splicing to produce dystrophin. Approximately 4% of patients with DMD may benefit from exon 50 skipping therapy. NS-050/NCNP-03 is an antisense oligonucleotide designed to treat patients who are amenable to exon 50 skipping. Here, we describe the study design of a recently initiated Phase 1/2 study evaluating NS-050/NCNP-03 in eligible participants with DMD.

Methods: This Phase 1/2, first-in-human, multicenter, 2-part study (NCT06053814) will evaluate the safety, efficacy, tolerability, pharmacodynamics, pharmacokinetics, and efficacy of NS-050/NCNP-03 in ambulant boys with DMD. Eligible participants are males aged ≥4 to <15 years with a confirmed DMD gene mutation amenable to exon 50 skipping. Participants must be able to walk independently and complete the time-to-stand assessment in <7 seconds without assistance. Key exclusion criteria include symptomatic cardiomyopathy, recent treatment with investigational drugs or gene therapies, and recent surgery. In Part 1, a randomized, double-blinded study where 9 participants will be randomized to receive escalating intravenous doses of NS-050/NCNP-03 or placebo once-weekly for 2 weeks/dose level, the primary objectives are evaluating safety, tolerability, and pharmacokinetics. In Part 2, 11 additional participants (N = 20, including participants from Part 1) will receive the maximum-tolerated dose (from Part 1) once-weekly for 24 weeks. The primary objective for Part 2 is to evaluate dystrophin protein levels in skeletal muscle; secondary objectives include assessing safety, tolerability, dystrophin mRNA induction, and strength/mobility vs a group-matched natural history control group. Conclusion: This Phase 1/2 study is a first-in-human trial to evaluate safety, tolerability, pharmacodynamics, pharmacokinetics, and efficacy of an exon 50 skipping therapy in ambulatory boys with DMD.