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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01957059
• Date of registration: 02/07/2013
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: A Phase I/II Study of BMN053 in Subjects With Duchenne Muscular Dystrophy (DMD)
• Scientific title: A Phase I/II, Open-label, Dose Escalating With 48 Week Treatment Study to Assess the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of BMN053 (Previously Known as PRO053) in Subjects With Duchenne Muscular Dystrophy.
• Date of first enrolment: June 2013
• Target sample size: 9
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01957059
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, France, Italy, Netherlands, United Kingdom

Contacts

• Name: V. Straub, Prof.
• Affiliation: Institute of Genetic Medicine, Newcastle University, UK

Key inclusion & exclusion 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.



Age minimum: 5 Years
Age maximum: 18 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: Regimen Selection Phase Group 1 (COMPLETED)

Drug: Dosing Extension

Drug: Treatment Phase Group 4

Drug: Regimen Selection Phase Group 3

Drug: Regimen Selection Phase Group 2

Primary Outcome(s)

Change from baseline in 6 minute walk test [Time Frame: after 48 weeks of treatment phase]

Secondary Outcome(s)

Pharmacokinetic parameters at different dose levels [Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase]

Cardiac function [Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase]

Safety Laboratory [Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase]

Functional outcomes questionnaire [Time Frame: after 48 weeks treatment phase]

Muscle strength [Time Frame: after 48 weeks treatment phase]

Adverse Events [Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase]

Muscle function [Time Frame: after 48 weeks treatment phase]

Presence of (BMD-like) dystrophin expression in muscle biopsy [Time Frame: after 48 weeks treatment phase]

Production of exon skip 53 mRNA in muscle biopsy [Time Frame: after 48 weeks treatment phase]

Pulmonary function [Time Frame: after 48 weeks treatment phase]

Secondary ID(s)

PRO053-CLIN-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors