Clinical trial NCT05996003: NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)
Official title: A Phase 2 Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NS-089/NCNP-02 in Boys With Duchenne Muscular Dystrophy (DMD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: NS Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nippon Shinyaku Co., Ltd.
First posted: 2023-08-16
Enrollment: 20
Sex: MALE
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Having received exon skipping oligonucleotide within 1 year prior to the first dose of IP or is expected to receive exon skipping oligonucleotide prior to completion of study.
* Other exclusion criteria may apply.

Primary outcomes:
measure: Adverse Event and Adverse Drug Reaction
timeFrame: through study completion, up to follow-up phone call for Part 2
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration (Tmax) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: [Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: 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
measure: Urine pharmacokinetic parameters
timeFrame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02
measure: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).
timeFrame: Baseline, Week25
Secondary outcomes:
measure: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.
timeFrame: Baseline, Week25
measure: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.
timeFrame: Baseline, Week25
measure: Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin
timeFrame: Baseline, Week25
measure: North Star Ambulatory Assessment (NSAA) score
timeFrame: Baseline, Week13, Week25
measure: Time to Run/Walk 10 Meters (TTRW)
timeFrame: Baseline, Week13, Week25
measure: Time to Stand (TTSTAND)
timeFrame: Baseline, Week13, Week25
measure: Total distance of 6 Minute Walk Test (6MWT)
timeFrame: Baseline, Week13, Week25
measure: Time to Climb 4 Stairs (TTCLIMB)
timeFrame: Baseline, Week13, Week25
measure: Muscle strength measured by Quantitative Muscle Testing (QMT)
timeFrame: Baseline, Week13, Week25
measure: Grip and pinch strength
timeFrame: Baseline, Week13, Week25
measure: Performance of Upper Limb (PUL) 2.0. score
timeFrame: Baseline, Week13, Week25
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern/Children's Health
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
Study officials:
References: