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

Primary Purpose

Duchenne Muscular Dystrophy

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

NS-089/NCNP-02

About this trial

This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne Muscular Dystrophy

Eligibility Criteria

4 Years - 17 Years (Child)MaleDoes not accept healthy volunteers

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.

Sites / Locations

National Center of Neurology and Psychiatry

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NS-089/NCNP-02

Arm Description

NS-089/NCNP-02

Outcomes

Primary Outcome Measures

Adverse event and adverse drug reaction [Safety and Tolerability]

adverse event and adverse drug reaction

Secondary Outcome Measures

Expression of dystrophin protein

NSAA

North Star Ambulatory Assessment

TTSTAND

Time to Stand Test

TTRW

Time to Run/Walk 10 Meters test

6MWT and 2MWT

Six-Minute Walk Test (6MWT) and Two-Minute Walk Test (2MWT)

TUG

Timed Up & Go (TUG) test

PUL

Performance of Upper Limb test

Detection of exon 44-skipped mRNA of dystrophin in muscle tissue

NS-089/NCNP-02 concentration of the blood plasma

Serum Creatine kinase concentration

Full Information

NCT ID

NCT04129294

First Posted

October 15, 2019

Last Updated

September 28, 2022

Sponsor

National Center of Neurology and Psychiatry, Japan

Collaborators

Nippon Shinyaku Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04129294

Brief Title

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

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

December 2, 2019 (Actual)

Primary Completion Date

May 31, 2022 (Actual)

Study Completion Date

May 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Center of Neurology and Psychiatry, Japan

Collaborators

Nippon Shinyaku Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NS-089/NCNP-02

Arm Type

Experimental

Arm Description

NS-089/NCNP-02

Intervention Type

Drug

Intervention Name(s)

NS-089/NCNP-02

Intervention Description

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."

Primary Outcome Measure Information:

Title

Adverse event and adverse drug reaction [Safety and Tolerability]

Description

adverse event and adverse drug reaction

Time Frame

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

Secondary Outcome Measure Information:

Title

Expression of dystrophin protein

Description

Expression of dystrophin protein

Time Frame