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

Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: NS-089/NCNP-02

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Kodaira, Tokyo, Japan, 1878551
      • National Center of Neurology and Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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."

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Center of Neurology and Psychiatry, Japan
• Collaborators: Nippon Shinyaku Co., Ltd.
• Investigators: Principal Investigator: Hirofumi Komaki, MD, PhD, National Center of Neurology and Psychiatry, Japan

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2019
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: NCNP/DMT02; UMIN000038505 (Other Identifier: UMIN-CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No