Duchenne Muscular Dystrophy
Conditions
Brief summary
This is a Phase 1/2 study of Multiple-Ascending Dose (MAD) levels for 12 weeks of treatment followed by 24 weeks of open-label treatment with a selected dose of NS-050/NCNP-03 administered once weekly to ambulant boys with DMD, who have a DMD exon deletion amenable to exon 50 skipping.
Interventions
DRUGNS-050/NCNP-03
NS-050/NCNP-03 solution for IV infusion.
DRUGPlacebo
NS-050/NCNP-03 placebo-matching solution for IV infusion.
Sponsors
NS Pharma, Inc.
Nippon Shinyaku Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
4 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Male ≥ 4 years and \<16 years of age; * Confirmed DMD exon deletion in the dystrophin gene that is amenable to skipping of exon 50 to restore the dystrophin mRNA reading frame; * Able to walk independently without assistive devices; * Able to complete the TTSTAND without assistance in \<20 seconds; * Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain on a stable dose for the duration of the study. Other inclusion criteria may apply.
Exclusion criteria
* Evidence of symptomatic cardiomyopathy; * Current or previous treatment with anabolic steroids (e.g., oxendolone, oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug; * Currently taking another investigational drug or has taken another investigational drug within 3 months prior to the first dose of study drug; * Surgery within the 3 months prior to the first dose of study drug or planned during the study duration; * Having taken any gene therapy. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Baseline up to Week 24 | TEAEs will be summarized both at the patient level for number of TEAEs, highest severity, relationship, action, and outcome, and at the TEAE level (summarizing events) by system organ class (SOC) and preferred term (PT) as well as severity, relationship, action, and outcome. The most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) will be used for coding TEAEs. |
| Part 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of NS-050/NCNP-03 | Day 1 (1st dose) for each dose level | Blood samples will be collected at the designated time frame. Pharmacokinetic (PK) parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods. |
| Part 1: Amount of Drug Excreted in Urine of NS-050/NCNP-03 | Day 1 (1st dose) for each dose level | Urine samples will be collected at the designated time frame. PK parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods. |
| Part 2: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot) | Baseline, Week25 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry | Baseline, Week25 | — |
| Part 2: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining | Baseline, Week25 | — |
| Part 2: Change from baseline in percentage of exon 50-skipped mRNA of skeletal muscle dystrophin | Baseline, Week25 | — |
| Part 2: North Star Ambulatory Assessment (NSAA) score | Baseline, Week13, Week25 | The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function. |
| Part 2: Time to Stand (TTSTAND) | Baseline, Week13, Week25 | — |
| Part 2: Time to Run/Walk 10 Meters (TTRW) | Baseline, Week13, Week25 | — |
| Part 2: Time to Climb 4 Stairs (TTCLIMB) | Baseline, Week13, Week25 | — |
| Part 2: Total distance of 6 Minute Walk Test (6MWT) | Baseline, Week13, Week25 | — |
| Part 2: Muscle strength measured by Quantitative Muscle Testing (QMT) | Baseline, Week13, Week25 | — |
| Part 2: Grip/Pinch Strength | Baseline, Week13, Week25 | — |
| Part 2: Performance of Upper Limb (PUL) 2.0. score | Baseline, Week13, Week25 | The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0 2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42). |
Countries
Canada, Japan, South Korea, Turkey (Türkiye), United States
Outcome results
None listed