Exploratory Study of NS-089/NCNP-02 in DMD

NCT04129294 | Completed Phase 1

• 2 other identifiers: NCNP/DMT02UMIN000038505
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-089/NCNP-02 in subjects diagnosed with Duchenne muscular dystrophy (DMD), and to determine the dosage for subsequent studies.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Adverse event and adverse drug reaction [Safety and Tolerability]

  adverse event and adverse drug reaction

  At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)

Secondary Outcomes (10)

• Expression of dystrophin protein

  At the end of the treatment period (24 weeks) of Part 2

• NSAA

  At the end of the treatment period (24 weeks) of Part 2

• TTSTAND

  At the end of the treatment period (24 weeks) of Part 2

• TTRW

  At the end of the treatment period (24 weeks) of Part 2

• 6MWT and 2MWT

  At the end of the treatment period (24 weeks) of Part 2

Study Arms (1)

NS-089/NCNP-02

EXPERIMENTAL

NS-089/NCNP-02

Drug: NS-089/NCNP-02

Interventions

NS-089/NCNP-02 DRUG

NS-089/NCNP-02 for Infusion is packaged as 50 mg/mL with 3 mL per vial. Study dosages will be infused over a 1 hour period at the following dose levels. "\[Part 1\] NS-089/NCNP-02 is administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2. Dose level 1: 1.62 mg/kg once weekly for 2 weeks; Dose level 2: 10 mg/kg once weekly for 2 weeks; Dose level 3: 40 mg/kg once weekly for 2 weeks; Dose level 4: 80 mg/kg once weekly for 2 weeks \[Part 2\] Based on the results from Part 1, two dosages are selected as study dosages in Part 2. Each selected dose are administered once a week for 24 weeks."

NS-089/NCNP-02

Eligibility Criteria

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

You may qualify if:

• Has an out of frame deletion(s) that could be corrected by skipping exon 44 as confirmed by any of methodology at the time of visit 1. If not confirmed by any of methodology that evaluates the relative copy number of all exons (i.e. MLPA etc), must be confirmed through these techniques by the time of visit 3.
• DNA sequencing of exon 44 confirms that no DNA polymorphisms occur that could compromise duplex formation between NS-089/NCNP-02 and pre-mRNA.
• Male and \>= 8 years and \< 17 years of age at the time of obtaining informed consent and/or assent. Subjects aged \>= 4 years and \< 8 years can be enrolled according to the circumstances.
• Able to give informed consent in writing signed by parent(s) or legal guardian who is able to understand all of the study procedure requirements. If applicable, able to give informed assent in writing signed by the subject.
• Life expectancy of at least 1 year
• Able to ambulate. Non-ambulant subject can be enrolled according to the circumstances.
• Have intact muscles, which have adequate quality for biopsy. (No lacks or severe atrophy of biceps brachii or tibialis anterior muscle)
• QTc \<450 msec (based on 12-lead ECGs), or \<480 msec for subject with Bundle Branch Block.
• Glucocorticoid-naive patients, or patients who have used systemic glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.

You may not qualify if:

• Has participated in other pharmacological clinical trial that might recover dystrophin protein by the readthrough or the exon-skipping therapy, and/or upregulate the dystrophin-associated proteins such as utrophin.
• A forced vital capacity (FVC) \< 50% of predicted.
• Continuous use of artificial respirator (except for use of NPPV while sleeping)
• A left ventricular ejection fraction (EF) \< 40% or fractional shortening (FS) \< 25% based on echocardiogram (ECHO).
• Surgery within the last 3 months prior to the first anticipated administration of study medication or planned for anytime between visit 1 of Part 1 and the last visit of Part 2.
• Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at screening.
• Current diagnosis of any immune deficiency or autoimmune disease.
• Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or renal disease.
• Use of any other investigational agents and/or experimental agents within 3 months prior to the first anticipated administration of study medication.
• History of any severe drug allergy.

Sponsors & Collaborators

• National Center of Neurology and Psychiatry, Japan: lead
• Nippon Shinyaku Co., Ltd.: collaborator

Study Sites (1)

National Center of Neurology and Psychiatry

Kodaira, Tokyo, 1878551, Japan

Location

Related Publications (2)

• Komaki H, Takeshita E, Kunitake K, Ishizuka T, Shimizu-Motohashi Y, Ishiyama A, Sasaki M, Yonee C, Maruyama S, Hida E, Aoki Y. Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy. Cell Rep Med. 2025 Jan 21;6(1):101901. doi: 10.1016/j.xcrm.2024.101901. Epub 2025 Jan 9.

  PMID: 39793573 DERIVED

• Ishizuka T, Komaki H, Asahina Y, Nakamura H, Motohashi N, Takeshita E, Shimizu-Motohashi Y, Ishiyama A, Yonee C, Maruyama S, Hida E, Aoki Y. Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/II clinical trial. Neuropsychopharmacol Rep. 2023 Jun;43(2):277-286. doi: 10.1002/npr2.12335. Epub 2023 Apr 3.

  PMID: 37326950 DERIVED

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 Officials

• Hirofumi Komaki, MD, PhD

  National Center of Neurology and Psychiatry, Japan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: December 2, 2019
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)