NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)
- Conditions
- Duchenne Muscular Dystrophy
- Interventions
- Drug: NS-089/NCNP-02
- Registration Number
- NCT05996003
- Lead Sponsor
- NS Pharma, Inc.
- Brief Summary
This is a Phase 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by weekly IV infusion to ambulant boys aged ≥4 to \<15 years with DMD due to mutations amenable to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered once weekly.
The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part 2.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 20
- Male ≥ 4 years and <15 years of age
- Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 44 to restore the dystrophin mRNA reading frame
- Able to walk independently without assistive devices
- Ability 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.
- Has a body weight of <20 kg at the time of informed consent (applies to participants screening for Part 1 only)
- Evidence of symptomatic cardiomyopathy
- Current or previous treatment with anabolic steroids (e.g., oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug
- Current or previous treatment with any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer
- Surgery within the 3 months prior to the first dose of study drug or planned during the study duration
- Previously treated in an interventional study of NS-089/NCNP-02
- Having taken any gene therapy or other exon-skipping oligonucleotide
- Other exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NS-089/NCNP-02 NS-089/NCNP-02 Experimental: NS-089/NCNP-02 NS-089/NCNP-02 solution for infusion (Cohort 1) NS-089/NCNP-02 solution for infusion (Cohort 2)
- Primary Outcome Measures
Name Time Method Urine pharmacokinetic parameters Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02 Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot). Baseline, Week25 Adverse Event and Adverse Drug Reaction through study completion, up to follow-up phone call for Part 2 Plasma pharmacokinetic (PK) parameters Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The volume in the terminal state (Vz) of NS-089/NCNP-02
- Secondary Outcome Measures
Name Time Method Muscle strength measured by Quantitative Muscle Testing (QMT) Baseline, Week13, Week25 Change from baseline in skeletal muscle dystrophin protein by mass spectrometry. Baseline, Week25 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.
Time to Stand (TTSTAND) Baseline, Week13, Week25 Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining. Baseline, Week25 Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin Baseline, Week25 Time to Run/Walk 10 Meters (TTRW) Baseline, Week13, Week25 Total distance of 6 Minute Walk Test (6MWT) Baseline, Week13, Week25 Time to Climb 4 Stairs (TTCLIMB) Baseline, Week13, Week25 Grip and pinch strength Baseline, Week13, Week25 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).
Trial Locations
- Locations (9)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Rare Disease Research
🇺🇸Atlanta, Georgia, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center (KUMC)
🇺🇸Kansas City, Kansas, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Shriners Hospital for Children
🇺🇸Portland, Oregon, United States
University of Pittsburgh School of Medicine
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern/Children's Health
🇺🇸Dallas, Texas, United States
Virginia Commonwealth University Health System
🇺🇸Richmond, Virginia, United States