A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration

A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration

The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.

Inclusion Criteria:

• Boys aged between 5 and 16 years inclusive.
• Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051.
• Not ventilator dependent.
• Life expectancy of at least six months.
• No previous treatment with investigational medicinal treatment within six months prior to the study.
• Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening.
• Known presence of dystrophin in 5% of fibers in a pre-study diagnostic muscle biopsy.
• Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
• FEV1 and/or FVC <60% of predicted.
• Current or history of liver or renal disease.
• Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
• Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
• Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
• Need for mechanical ventilation.
• Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
• Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
• Use of anticoagulants, antithrombotics or antiplatelet agents.
• Subject has donated blood less than 90 days before the start of the study.
• Current or history of drug and/or alcohol abuse.
• Participation in another trial with an investigational product.