Clinical trial: Phase II Study of NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy (NCT01918384)

Eligibility criteria:
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
Male
No healthy subjects accepted to join the trial.
Subject must be at least 4 Years old.


Patient description (medical language): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient description (patient's own words): I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Does the patient match the trial criteria? Entailment