NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05996003
• Other study ID #: NS-089/NCNP-02-201
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2024
• Est. completion date: November 28, 2025

Study information

• Verified date: March 2024
• Source: NS Pharma, Inc.
• Contact: Trial info
• Phone: 1-866-677-6276
• Email: trialinfo[@]nspharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 28, 2025
• Est. primary completion date: November 28, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 14 Years

Eligibility

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 <7 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 or other exon-skipping oligonucleotide

• Other exclusion criteria may apply.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• NS-089/NCNP-02
Cohort 1: Part 1 Dose Level 1-3: a 4-week Treatment Phase at each treatment dose level Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1 Cohort 2: Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1

Locations

Country	Name	City	State
United States	Rare Disease Research	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	UT Southwestern/Children's Health	Dallas	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Shriners Hospital for Children	Portland	Oregon
United States	Virginia Commonwealth University Health System	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
NS Pharma, Inc.	Nippon Shinyaku Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Event and Adverse Drug Reaction		through study completion, up to follow-up phone call for Part 2
Primary	Plasma pharmacokinetic (PK) parameters		Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02
Primary	Plasma pharmacokinetic (PK) parameters		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
Primary	Plasma pharmacokinetic (PK) parameters		Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02
Primary	Plasma pharmacokinetic (PK) parameters		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
Primary	Plasma pharmacokinetic (PK) parameters		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 (AUC0-8) of NS-089/NCNP-02
Primary	Plasma pharmacokinetic (PK) parameters		[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
Primary	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
Primary	Urine pharmacokinetic parameters		Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02
Primary	Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).		Baseline, Week25
Secondary	Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.		Baseline, Week25
Secondary	Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.		Baseline, Week25
Secondary	Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin		Baseline, Week25
Secondary	North Star Ambulatory Assessment (NSAA) score	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.	Baseline, Week13, Week25
Secondary	Time to Run/Walk 10 Meters (TTRW)		Baseline, Week13, Week25
Secondary	Time to Stand (TTSTAND)		Baseline, Week13, Week25
Secondary	Total distance of 6 Minute Walk Test (6MWT)		Baseline, Week13, Week25
Secondary	Time to Climb 4 Stairs (TTCLIMB)		Baseline, Week13, Week25
Secondary	Muscle strength measured by Quantitative Muscle Testing (QMT)		Baseline, Week13, Week25
Secondary	Grip and pinch strength		Baseline, Week13, Week25
Secondary	Performance of Upper Limb (PUL) 2.0. score	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).	Baseline, Week13, Week25