Journal article
Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy
Annals of clinical and translational neurology, Vol.5(8), pp.913-926
08/2018
DOI: 10.1002/acn3.579
PMCID: PMC6093847
PMID: 30128316
Abstract
This double-blind, randomized, placebo-controlled Phase 2 study (NCT01462292) assessed the 24-week efficacy, safety, tolerability, and pharmacokinetics of two different subcutaneous drisapersen doses, and the 24-week off-dose persistent effect, in ambulant Duchenne muscular dystrophy (DMD) patients.
Male DMD patients (≥5 years; time to rise from floor ≤15 s) were randomized to drisapersen 3 mg/kg/week, 6 mg/kg/week or placebo. The primary efficacy endpoint was change from baseline in 6-minute walking distance (6MWD) at week 24. Secondary endpoints included changes in timed function tests, muscle strength, and pulmonary function tests.
Fifty-one patients were randomized to placebo (
= 16), drisapersen 3 mg/kg/week (
= 17) or 6 mg/kg/week (
= 18). All but 2 patients had baseline rise from floor time <7 s. This study was exploratory and not prospectively powered; however, a difference in mean 6MWD versus placebo in favor of drisapersen 6 mg/kg/week was observed at week 24 (27.1 m;
= 0.069) and maintained 24 weeks off-treatment (27.9 m;
= 0.177). The 3 mg/kg/week group showed no statistically significant difference in mean 6MWD versus placebo. For some secondary endpoints, a more positive response in favor of drisapersen 6 mg/kg/week compared to placebo was shown. Drisapersen had a long half-life with steady state reached after approximately 36 weeks. Most common adverse events in both drisapersen groups were related to injection site reactions and subclinical proteinuria.
Drisapersen 6 mg/kg/week for 24 weeks resulted in a treatment benefit in 6MWD, largely maintained 24 weeks off-treatment. This study provided insights for further studies to optimize dosage regimen.
Details
- Title: Subtitle
- Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy
- Creators
- Craig M McDonald - University of California, Davis Sacramento CaliforniaBrenda Wong - Cincinnati Children's Hospital Cincinnati OhioKevin M Flanigan - Nationwide Children's Hospital Columbus OhioRosamund Wilson - Spica Consultants Ltd Marlborough United KingdomSjef de Kimpe - BioMarin Nederland B.V. Leiden The NetherlandsAfrodite Lourbakos - BioMarin Nederland B.V. Leiden The NetherlandsZhengning Lin - BioMarin Nederland B.V. Leiden The NetherlandsGiles Campion - BioMarin Nederland B.V. Leiden The NetherlandsDEMAND V study group
- Contributors
- Katherine D Mathews (Contributor) - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.5(8), pp.913-926
- DOI
- 10.1002/acn3.579
- PMID
- 30128316
- PMCID
- PMC6093847
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Publisher
- United States
- Grant note
- UL1 TR001070 / NCATS NIH HHS
- Language
- English
- Date published
- 08/2018
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070533202771
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