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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 October 2022
• Main ID: NCT04129294
• Date of registration: 15/10/2019
• Prospective Registration: Yes
• Primary sponsor: National Center of Neurology and Psychiatry, Japan
• Public title: Exploratory Study of NS-089/NCNP-02 in DMD
• Scientific title: Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
• Date of first enrolment: December 2, 2019
• Target sample size: 6
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT04129294
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Japan

Contacts

• Name: Hirofumi Komaki, MD, PhD
• Affiliation: National Center of Neurology and Psychiatry, Japan

Key inclusion & exclusion 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.



Age minimum: 4 Years
Age maximum: 17 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: NS-089/NCNP-02

Primary Outcome(s)

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)]

Secondary Outcome(s)

Serum Creatine kinase concentration [Time Frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)]

TUG [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

6MWT and 2MWT [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

NSAA [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 [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

TTSTAND [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

Expression of dystrophin protein [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

PUL [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

TTRW [Time Frame: At the end of the treatment period (24 weeks) of Part 2]

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)]

Secondary ID(s)

UMIN000038505

NCNP/DMT02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Nippon Shinyaku Co., Ltd.