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

NCT05996003 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NS-089/NCNP-02-201
• Study Type: interventional
• Target: 20
• Locations: 7 countries
• Sites: 29

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.

Conditions

Duchenne Muscular Dystrophy; Exon 44; DMD

Keywords

Exon 44 Skipping; DMD; Brogidirsen

Outcome Measures

Primary Outcomes (10)

• 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] Maximum plasma concentration (Cmax) of NS-089/NCNP-02

• 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

• 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

• 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

• 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-∞) of NS-089/NCNP-02

• Plasma pharmacokinetic (PK) parameters

  Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02

• 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

• 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

Secondary Outcomes (11)

• Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.

  Baseline, 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

• North Star Ambulatory Assessment (NSAA) score

  Baseline, Week13, Week25

• Time to Run/Walk 10 Meters (TTRW)

  Baseline, Week13, Week25

Study Arms (1)

NS-089/NCNP-02

EXPERIMENTAL

Experimental: NS-089/NCNP-02 NS-089/NCNP-02 solution for infusion (Cohort 1) NS-089/NCNP-02 solution for infusion (Cohort 2)

Drug: NS-089/NCNP-02

Interventions

NS-089/NCNP-02 DRUG

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

Also known as: Brogidirsen

NS-089/NCNP-02

Eligibility Criteria

• Age: 4 Years - 14 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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 received exon skipping oligonucleotide within 1 year prior to the first dose of IP

Sponsors & Collaborators

• NS Pharma, Inc.: lead
• Nippon Shinyaku Co., Ltd.: collaborator

Study Sites (29)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, 66160, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Pediatric Neuromuscular Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15224, United States

Location

UT Southwestern/Children's Health

Dallas, Texas, 75207, United States

Location

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Fukui Prefectural Hospital

Fukui-shi, Fukui, 910-8526, Japan

Location

National Hospital Organization Nagara Medical Center

Nagara, Gifu-shi, Gifu, 502-8558, Japan

Location

NHO Osaka Toneyama Medical Center

Toyonaka, Osaka, 560-8552, Japan

Location

Shiga General Hospital

Moriyama-shi, Shiga, 524-8524, Japan

Location

National Center of Neurology and Psychiatry

Kodaira, Tokyo, 187-8551, Japan

Location

Starship Children's Hospital

Auckland, 1023, New Zealand

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Ankara Bilkent City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Istanbul University- Istanbul Faculty of Medicine

Istanbul, 34093, Turkey (Türkiye)

Location

Yeditepe University Kosuyolu Hospital

Istanbul, 34718, Turkey (Türkiye)

Location

S.B.U. Dr. Behcet uz Pediatric Diseases and Surgery Training and Research Hospital

Izmir, 11794, Turkey (Türkiye)

Location

Related Links

• Please follow this link for additional information on how to participate

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2023
• First Posted: August 16, 2023
• Study Start: February 22, 2024
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: September 15, 2026

Record last verified: 2026-09

Locations

US (11); KR (3); TU (4); AU (2); JP (5); NZ (1); CA (3)