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Phase II Study of NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy (NORTH POLE 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. Identifier: NCT01918384
Recruitment Status : Unknown
Verified September 2015 by Yasuhiro Takeshima, Kobe University.
Recruitment status was:  Active, not recruiting
First Posted : August 7, 2013
Last Update Posted : September 3, 2015
Japan Medical Association
Information provided by (Responsible Party):
Yasuhiro Takeshima, Kobe University

Brief Summary:
Duchenne Muscular Dystrophy (DMD) is inherited neuromuscular disorders due to mutation in the gene that encodes critical muscle protein called dystrophin. Currently, there is no effective treatment option for the disease. A pharmacological approach by promoting mRNA translation regardless of the presence of premature stop codons by nonsense mutation, called the readthrough strategy, has been developing recently for DMD with nonsense mutation. NPC-14 is a candidate compound for the readthrough strategy, since effective readthrough activities were demonstrated in nonclinical studies. This study is a phase II study designed to assess safety, tolerability, and efficacy of NPC-14 in ambulant DMD patients with nonsense mutation that were confirmed by whole genome analysis. These goals will be accomplished by monitoring adverse events by physical examination, cardiac, pulmonary, auditory, balance, and laboratory tests as safety endpoints, and dystrophin expression in muscle biopsy as primary efficacy endpoint, muscle function (NSAA, timed test, muscle strength (QMT, MMT) , dairy activities by lifecorder), and biomarkers as secondary efficacy endpoints. The study is a randomized, double blind, placebo-controlled study in 21 DMD patients. After screening, eligible patients are allocated dynamically to weekly NPC-14 or a placebo (saline) in a 2:1 ratio and will receive study drugs for 36 weeks.

Condition or disease Intervention/treatment Phase
Muscular Dystrophy, Duchenne Drug: NPC-14 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of Nonsense Readthrough Compound NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy Patients (NORTH POLE DMD Study)
Study Start Date : August 2013
Estimated Primary Completion Date : October 2015
Estimated Study Completion Date : October 2015

Arm Intervention/treatment
Experimental: NPC-14
Intravenous drip, QW, 36 weeks, Dose will be adjusted and maintained by therapeutic drug monitoring of peak serum levels of NPC-14
Drug: NPC-14

NPC-14 will be administrated as following steps. The dose of NPC-14 will be calculated and adjusted by a non-blinded medical doctor and/or a non-blinded pharmacist.

  • An initial dose of NPC-14 will be half of that calculated by distribution volume:Vd based on patient age for safety reason.
  • After the initial administration, the dose of NPC-14 will be adjusted and maintained by actual Vd, therapeutic drug monitoring of peak serum levels of NPC-14
Other Name: Arbekacin

Placebo Comparator: Placebo
Dose will be adjusted by volume of distribution (Vd) of patients in accordance with the NPC-14 dose regimen
Drug: Placebo
Dose will be adjusted by volume of distribution (Vd) of patients in accordance with the NPC-14 dose regimen

Primary Outcome Measures :
  1. Safety and tolerability (Adverse events) [ Time Frame: Up to 38 weeks (36 weeks treatment period and 2 weeks follow up period) ]
  2. Change of dystrophin expression rate in muscle tissues from the baseline assessment [ Time Frame: At 37 weeks (1 week after from 36 weeks treatment period) ]

Secondary Outcome Measures :
  1. North Star Ambulatory Assessment [ Time Frame: At 36 weeks ]
  2. Timed test (6MWT, time to walk/run 10 meters, time to climb/descent four steps, time to rise from the floor) [ Time Frame: At 36 weeks ]
  3. Muscle strength (MMT, QMT) [ Time Frame: At 36 weeks ]
  4. Dairy activities [ Time Frame: At 36 weeks ]
  5. Biomarkers (CK, ALD) [ Time Frame: At 36 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of DMD resulting from a nonsense mutation by whole genome sequencing of the dystrophin gene
  2. To have intact right or left biceps muscles, or an alternative muscle group that is able to be underwent for appropriate evaluation of efficacy
  3. To meet the following criteria at screening (baseline visit), within 30 days prior to the first dose of study drug

    • Ambulant and able to walk at least 75 meters during the 6MWT
    • Able to comply with and complete all protocol requirements, and judged by the investigator to be appropriate to participate in the study from the screening results
  4. Aged at least 4 years at the time of giving informed consent
  5. Male
  6. Able to be hospitalized for the study requirement
  7. Signed Informed consent by parents/legal guardian and/or signed assent by the subject (age of assent to be determined by IRB)

Exclusion Criteria:

  1. Prior exposure to investigational medicines that have a potential of restoring dystrophin or other functional protein (readthrough, exon skipping, utrophin upregulation therapy etc.)
  2. Known mutation at nucleotide 1555 in 12S rRNA gene of mitochondrial DNA, and/or personally or families have been treated or have a history of eight cranial nerve disorder (hearing loss、vertigo、tinnitus etc.)as a result of aminoglycoside use
  3. Inability to hear within the range of 0 to 25 dB by pure tone audiometry, abnormalities on auditory brainstem response audiometry, and/or loss of frequency by distortion product oto acoustic emissions at screening
  4. Poor oral intake or enable to oral intake, and/or bad general status
  5. Known allergies to NPC-14, other aminoglycosides, and/or bacitracin
  6. Presence of anti-dystrophin antibody at the baseline assessments
  7. Cys-C ≥1.2 mg/L and/or creatinine concentration >1.5 times the upper limit of age corrected normal range
  8. Left ventricular ejection fraction (EF) <40% or left ventricular fractional shortening (FS) <25%, and/or ≥480 msec QTc (corrected QT interval by Fridericia's method)
  9. Need of mechanical ventilation
  10. Forced vital capacity (FVC) <50% predicted
  11. Clinically significant concomitant diseases (hematology, psychoneurotic, hepatic, pulmonary, endocrine, immune, renal, and gastroenterological diseases), and/or cancer
  12. Impairment of intellectual functions, and/or expressive language ability which might interfere with study assessments
  13. Treatment with other systemic aminoglycoside within 6 months prior to the first administration of study drug
  14. Initiation of systemic glucocorticosteroids treatment, and/or start exercise cure, physical therapy, or occupational therapy which might interfere with study assessments. Changing of dose and schedule of systemic glucocorticosteroids within 6 months prior to the first administration of study drug
  15. History of any surgical procedure within months prior to the first administration of study drug or have a plan during study
  16. History of sever allergy from food and medicine like an anaphylaxis shock or generalized rash
  17. Participation in any other clinical trial and intake of any investigational drug within 6month of study entry

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 identifier (NCT number): NCT01918384

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Kobe university hospital, department of pediatrics
Kobe, Hyogo prefecture, Japan, 650-0017
Hyogo College of Medicine
Nishinomiya, Hyogo prefecture, Japan, 663-8501
National center of neurology and psychiatry
Kodaira, Tokyo, Japan, 187-8551
Tokyo Women's Medical University
Shinjuku-ku, Tokyo, Japan, 162-8666
Sponsors and Collaborators
Kobe University
Japan Medical Association
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Principal Investigator: Yasuhiro Takeshima, MD, PhD Hyogo College of Medicine
Study Director: Hirofumi Komaki, MD, PhD National center of neurology and psychiatry, department of child neurology, Muscular disease center
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Responsible Party: Yasuhiro Takeshima, MD, PhD, Kobe University Identifier: NCT01918384    
Other Study ID Numbers: NPC-14-1
JMA-IIA00134 ( Other Identifier: Center for clinical trials, Japan Medical Association )
First Posted: August 7, 2013    Key Record Dates
Last Update Posted: September 3, 2015
Last Verified: September 2015
Keywords provided by Yasuhiro Takeshima, Kobe University:
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
Anti-Infective Agents