Clinical trial NCT04129294: Exploratory Study of NS-089/NCNP-02 in DMD
Official title: Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy
Lead sponsor: National Center of Neurology and Psychiatry, Japan
Sponsor class: OTHER
Collaborators: name: Nippon Shinyaku Co., Ltd.
First posted: 2019-10-16
Enrollment: 6
Sex: MALE
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Adverse event and adverse drug reaction [Safety and Tolerability]
timeFrame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Secondary outcomes:
measure: Expression of dystrophin protein
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: NSAA
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: TTSTAND
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: TTRW
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: 6MWT and 2MWT
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: TUG
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: PUL
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: Detection of exon 44-skipped mRNA of dystrophin in muscle tissue
timeFrame: At the end of the treatment period (24 weeks) of Part 2
measure: NS-089/NCNP-02 concentration of the blood plasma
timeFrame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
measure: Serum Creatine kinase concentration
timeFrame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Other outcomes:
Locations:
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
Study officials:
affiliation: National Center of Neurology and Psychiatry, Japan
name: Hirofumi Komaki, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: