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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04129294
Recruitment Status : Enrolling by invitation
First Posted : October 16, 2019
Last Update Posted : December 4, 2019
Sponsor:
Collaborator:
Nippon Shinyaku Co., Ltd.
Information provided by (Responsible Party):
Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
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
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : December 31, 2021


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."





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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04129294


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

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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    Key Record Dates
Last Update Posted: December 4, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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