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

• ClinicalTrials.gov Identifier: NCT04129294
• Recruitment Status: Enrolling by invitation
• First Posted: October 16, 2019
• Last Update Posted: August 4, 2020
• Sponsor: National Center of Neurology and Psychiatry, Japan
• Collaborator: Nippon Shinyaku Co., Ltd.
• Information provided by (Responsible Party): Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan

Tracking Information

• First Submitted Date: October 15, 2019
• First Posted Date: October 16, 2019
• Last Update Posted Date: August 4, 2020
• Actual Study Start Date: December 2, 2019
• Estimated Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 6, 2019)

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

Original Primary Outcome Measures (submitted: October 15, 2019)

Safety and tolerability [ Time Frame: 36 weeks of Part 2 (24 weeks treatment period and 12 weeks follow up period) ]

adverse event and adverse drug reaction

Current Secondary Outcome Measures (submitted: November 6, 2019)

• Expression of dystrophin protein [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  Expression of dystrophin protein
• NSAA [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  North Star Ambulatory Assessment
• TTSTAND [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  Time to Stand Test
• TTRW [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  Time to Run/Walk 10 Meters test
• 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)
• TUG [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  Timed Up & Go (TUG) test
• PUL [ Time Frame: At the end of the treatment period (24 weeks) of Part 2 ]
  Performance of Upper Limb test
• 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
• 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
• 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

Original Secondary Outcome Measures (submitted: October 15, 2019)

• Expression of dystrophin protein [ Time Frame: Week 25-26 weeks of Part 2 ]
• North Star Ambulatory Assessment (NSAA) [ Time Frame: 25-26 weeks of Part 2 ]
• Time to Stand Test (TTSTAND) [ Time Frame: 25-26 weeks of Part 2 ]
• Time to Run/Walk 10 Meters test (TTRW) [ Time Frame: 25-26 weeks of Part 2 ]
• Six-Minute Walk Test (6MWT) and Two-Minute Walk Test (2MWT) [ Time Frame: 25-26 weeks of Part 2 ]
• Timed Up & Go (TUG) test [ Time Frame: 25-26 weeks of Part 2 ]
• Performance of Upper Limb (PUL) test [ Time Frame: 25-26 weeks of Part 2 ]
• Detection of exon 44-skipped mRNA of dystrophin in muscle tissue [ Time Frame: 25-26 weeks of Part 2 ]
• NS-089/NCNP-02 concentration of the blood plasma [ Time Frame: 36 weeks of Part 2 ]
• Serum Creatine kinase concentration [ Time Frame: 36 weeks of Part 2 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Exploratory Study of NS-089/NCNP-02 in DMD
• Official Title: Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

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."

Study Arms

Experimental: NS-089/NCNP-02

NS-089/NCNP-02

Intervention: Drug: NS-089/NCNP-02

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: October 15, 2019): 6
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 4 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04129294
• Other Study ID Numbers: NCNP/DMT02; UMIN000038505 ( Other Identifier: UMIN-CTR )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan
• Study 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

• PRS Account: National Center of Neurology and Psychiatry, Japan
• Verification Date: August 2020