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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 September 2015
• Main ID: NCT01918384
• Date of registration: 01/08/2013
• Prospective Registration: Yes
• Primary sponsor: Kobe University
• Public title: Phase II Study of NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy NORTH POLE DMD
• Scientific 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)
• Date of first enrolment: August 2013
• Target sample size: 21
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT01918384
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Japan

Contacts

• Name: Yasuhiro Takeshima, MD, PhD
• Affiliation: Hyogo College of Medicine

• Name: Hirofumi Komaki, MD, PhD
• Affiliation: National center of neurology and psychiatry, department of child neurology, Muscular disease center

Key inclusion & exclusion 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



Age minimum: 4 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Muscular Dystrophy, Duchenne

Intervention(s)

Drug: NPC-14

Drug: Placebo

Primary Outcome(s)

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)]

Safety and tolerability (Adverse events) [Time Frame: Up to 38 weeks (36 weeks treatment period and 2 weeks follow up period)]

Secondary Outcome(s)

Biomarkers (CK, ALD) [Time Frame: At 36 weeks]

Dairy activities [Time Frame: At 36 weeks]

Muscle strength (MMT, QMT) [Time Frame: At 36 weeks]

North Star Ambulatory Assessment [Time Frame: At 36 weeks]

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]

Secondary ID(s)

NPC-14-1

JMA-IIA00134

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Nobelpharma

Japan Medical Association