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
- Registration Number
- NCT01910649
- Lead Sponsor
- BioMarin Pharmaceutical
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 12
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Drisapersen Drisapersen Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration
- Primary Outcome Measures
Name Time Method Acute phase: Safety data 18 weeks Summarized per dose group
Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance 18 weeks Plasma concentration versus time profiles of PRO051 (GSK2402968)
Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs) 72 weeks Change from baseline and summarized values
Continued Treatment Phase :Safety as assessed by laboratory parameters 72 weeks Change from baseline and summarized values
- Secondary Outcome Measures
Name Time Method Continued Treatment Phase: Muscle function 300 weeks Timed tests and 6-minutes walk
Continued Treatment Phase: Muscle strength 300 weeks Handheld myometry and spirometry
Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA) 18 weeks Acute phase: Muscle function 18 weeks Timed tests and 6-minutes walk
Continued Treatment Phase Dystrophin expression in muscle biopsy 72 weeks Continued Treatment Phase: Exon skip efficiency 72 weeks Acute phase: Presence of dystrophin expression 18 weeks Acute phase: Muscle strength 18 weeks Quantitative Muscle Testing \[QMT\]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing \[MMT\]