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)
- Conditions
- Duchenne muscular dystrophy
- Registration Number
- JPRN-jRCT1091220134
- Lead Sponsor
- Yasuhiro Takeshima, MD, PhDHyogo College of Medicine Hospital, department of pediatrics
- Brief Summary
Good safety and tolerability of NPC-14 were shown in ambulant DMD patients by adjustment of dosage to 40 micro g/mL of Cmax. Change of dystrophin expression rate, which is primary outcome of NPC-14 effect, is difficult to be judged because of lower expression than sensitivity of the measurement. Assessment of dystrophin expression by more sensitive assay system is necessary.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 21
(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)
(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-dystophin 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 gminoglycoside 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method (Safety)Adverse events<br>(Efficacy)Dystrophin expression
- Secondary Outcome Measures
Name Time Method -NSAA<br>-Timed test <br>-MMT<br>-QMT<br>-Dairy activities by lifecorder<br>-Biomarkers