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

• ClinicalTrials.gov Identifier: NCT04129294
• Recruitment Status: Completed
• First Posted: October 16, 2019
• Last Update Posted: September 29, 2022
• Sponsor: National Center of Neurology and Psychiatry, Japan
• Collaborator: Nippon Shinyaku Co., Ltd.
• Information provided by (Responsible Party): Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: NS-089/NCNP-02	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
• Actual Study Start Date: December 2, 2019
• Actual Primary Completion Date: May 31, 2022
• Actual Study Completion Date: May 31, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: NS-089/NCNP-02; NS-089/NCNP-02

Drug: NS-089/NCNP-02; 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."

Outcome Measures

Primary Outcome Measures :

1. Adverse event and adverse drug reaction [Safety and Tolerability] [ Time Frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period) ]
   adverse event and adverse drug reaction

Secondary Outcome Measures :

1. Expression of dystrophin protein [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Expression of dystrophin protein
2. NSAA [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   North Star Ambulatory Assessment
3. TTSTAND [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Time to Stand Test
4. TTRW [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Time to Run/Walk 10 Meters test
5. 6MWT and 2MWT [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Six-Minute Walk Test (6MWT) and Two-Minute Walk Test (2MWT)
6. TUG [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Timed Up & Go (TUG) test
7. PUL [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Performance of Upper Limb test
8. Detection of exon 44-skipped mRNA of dystrophin in muscle tissue [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
   Detection of exon 44-skipped mRNA of dystrophin in muscle tissue
9. NS-089/NCNP-02 concentration of the blood plasma [ Time Frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period) ]
   NS-089/NCNP-02 concentration of the blood plasma
10. Serum Creatine kinase concentration [ Time Frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period) ]
    Serum Creatine kinase concentration

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

Japan

National Center of Neurology and Psychiatry

Kodaira, Tokyo, Japan, 1878551

Sponsors and Collaborators

National Center of Neurology and Psychiatry, Japan

Nippon Shinyaku Co., Ltd.

Investigators

• Principal Investigator: Hirofumi Komaki, MD, PhD; National Center of Neurology and Psychiatry, Japan

More Information

• Responsible Party: Hirofumi Komaki, Director, National Center of Neurology and Psychiatry, Japan
• ClinicalTrials.gov Identifier: NCT04129294
• Other Study ID Numbers: NCNP/DMT02; UMIN000038505 ( Other Identifier: UMIN-CTR )
• First Posted: October 16, 2019
• Last Update Posted: September 29, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan:

Duchenne Muscular Dystrophy

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked