Muscular Dystrophies
Conditions
Keywords
drisapersen
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.
Interventions
DRUGDrisapersen
Subcutaneous and Intravenous
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
5 Years to 16 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Continued Treatment Phase: Exon skip efficiency | 72 weeks | — |
| Continued Treatment Phase Dystrophin expression in muscle biopsy | 72 weeks | — |
| Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA) | 18 weeks | — |
| Continued Treatment Phase: Muscle strength | 300 weeks | Handheld myometry and spirometry |
| Continued Treatment Phase: Muscle function | 300 weeks | Timed tests and 6-minutes walk |
| Acute phase: Presence of dystrophin expression | 18 weeks | — |
| Acute phase: Muscle function | 18 weeks | Timed tests and 6-minutes walk |
| Acute phase: Muscle strength | 18 weeks | Quantitative Muscle Testing \[QMT\]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing \[MMT\] |
Outcome results
None listed