A Phase I/II Study of BMN053 in Subjects With Duchenne Muscular Dystrophy (DMD)

The purpose of the study is to see whether BMN053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein.

A Phase I/II, open-label, dose escalating with 48-week treatment study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of BMN 053 (previously known as PRO053) in subjects with Duchenne muscular dystrophy

Eligibility Criteria:
Inclusion Criteria:

1. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with BMN053 confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or HRMCA (High-Resolution Melting Curve Analysis).
2. Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 300 metres in the 6 minute walking distance (6MWD) test. In addition, results of the 6MWD test must be within ±30 metres of each other at 2 of 3 pre-treatment visits (screen 1, 2 and baseline) prior to first BMN053 administration.
3. Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. Only under exceptional circumstances will an alternative muscle (preferably brachii) be considered for biopsy and only following discussion between the Principal Investigator and the BioMarin Medical Monitor.
4. Life expectancy of at least 3 years after inclusion in the study.
5. Glucocorticosteroid use which is stable for at least 3 months prior to first BMN053 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first BMN053 administration.
6. Willing and able to adhere to the study visit schedule and other protocol requirements.
7. Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations).
8. In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
9. Anticipated adequate vein access for intravenous (IV) infusion.

Exclusion Criteria:

1. Current or history of liver disease or impairment.
2. Current or history of renal disease or impairment.
3. At least two aPTT above upper limit of normal (ULN) within the last month prior to first dose of BMN053.
4. Screening platelet count below the lower limit of normal (LLN).
5. Acute illness within 4 weeks prior to first dose of BMN053 which may interfere with the study assessments.
6. Severe mental retardation and/or behavioural problems which, in the opinion of the Investigator, prohibit participation in this study.
7. Severe cardiomyopathy which, in the opinion of the Investigator prohibits participation in this study. If a subject has a left ventricular ejection fraction \<45% at screening, the Investigator should discuss inclusion of the subject with the Medical Monitor.
8. Expected need for daytime mechanical ventilation within the next year.
9. Use of anticoagulants, antithrombotics or antiplatelet agents.
10. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.
11. Use of nutritional or herbal supplements which, in the opinion of the Investigator, may influence muscle performance within 1 month prior to first dose of BMN053.
12. Use of any other investigational product or participation in another trial with an investigational product, within 6 months prior to the start of the screening for the study.