Safety and Dose Finding Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)

The main objective of this study is to evaluate the safety of a high (80mg/kg) and low (40mg/kg) dose of NS-065/NCNP-01 delivered as an intravenous infusion in patients with Duchenne Muscular Dystrophy (DMD) amendable to exon 53 skipping. Additional objectives include tolerability, muscle function and strength, pharmacokinetics and pharmacodynamics.

This is a Phase II, multiple center, 2-period, randomized, placebo-controlled, dose finding study of NS-065/NCNP-01 administered by infusion once weekly for 24 weeks to ambulant boys ages 4-\<10 years with DMD. Two dose level cohorts will be enrolled. Period 1 of this study will be conducted in a double-blind fashion. Randomized patients will receive weekly IV infusions of NS-065/NCNP-01 or placebo for the first 4 weeks of their participation (Period 1) and NS-065/NCNP-01 by IV infusion for weeks 5-24 (20 weeks of active treatment - Period 2). Analysis of safety data from Period 1 of the 40mg/kg dose cohort will be completed prior to enrolling patients in the 80mg/kg dose cohort.

Patients completing the 24-week study will be eligible for an open-label extension study.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT), time to stand (TTSTAND), time to run/walk 10 meters (TTRW), time to climb 4 stairs (TTCLIMB) and quantitative muscle testing (QMT). All patients will undergo a muscle biopsy of the bicep at baseline and a second muscle biopsy at Week 24.

Safety will be assessed through the collection of adverse events (AEs), blood and urine laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations throughout the study.

Serial blood samples will be taken at four of the study visits to assess the pharmacokinetics of the study drug.

Eligibility Criteria:
Inclusion Criteria:

* Male ≥ 4 years and \<10 years of age
* Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin mRNA reading frame;
* Able to walk independently without assistive devices;
* Ability to complete the time to stand, time to run/walk and time to climb assessments;
* Stable dose of glucocorticoid for at least 3 months

Exclusion Criteria:

* Acute illness within 4 weeks prior to the first dose of study medication;
* Evidence of symptomatic cardiomyopathy. \[Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary\];
* Severe allergy or hypersensitivity to medications;
* Severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
* Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
* Patient is taking any other investigational drug currently or within 3 months prior to the start of study treatment; or
* Patient has had surgery within the 3 months prior to the first anticipated administration of study medication or surgery is planned for anytime during the duration of the study;
* Patient has previously participated in this study or any other study during which NS-065/NCNP-01 was administered.