Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy
OBJECTIVE: 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.
METHODS: 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.
RESULTS: Fifty-one patients were randomized to placebo (N = 16), drisapersen 3 mg/kg/week (N = 17) or 6 mg/kg/week (N = 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; P = 0.069) and maintained 24 weeks off-treatment (27.9 m; P = 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.
INTERPRETATION: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Annals of clinical and translational neurology - 5(2018), 8 vom: 16. Aug., Seite 913-926 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McDonald, Craig M [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 18.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1002/acn3.579 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM287669130 |
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| 245 | 1 | 0 | |a Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a OBJECTIVE: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: Fifty-one patients were randomized to placebo (N = 16), drisapersen 3 mg/kg/week (N = 17) or 6 mg/kg/week (N = 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; P = 0.069) and maintained 24 weeks off-treatment (27.9 m; P = 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 | ||
| 520 | |a INTERPRETATION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Wong, Brenda |e verfasserin |4 aut | |
| 700 | 1 | |a Flanigan, Kevin M |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Rosamund |e verfasserin |4 aut | |
| 700 | 1 | |a de Kimpe, Sjef |e verfasserin |4 aut | |
| 700 | 1 | |a Lourbakos, Afrodite |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhengning |e verfasserin |4 aut | |
| 700 | 1 | |a Campion, Giles |e verfasserin |4 aut | |
| 700 | 0 | |a DEMAND V study group |e verfasserin |4 aut | |
| 700 | 1 | |a Iannaccone, Susan T |e investigator |4 oth | |
| 700 | 1 | |a Karachunski, Peter I |e investigator |4 oth | |
| 700 | 1 | |a Mathews, Katherine D |e investigator |4 oth | |
| 700 | 1 | |a Henricson, Erik K |e investigator |4 oth | |
| 700 | 1 | |a Joyce, Nanette C |e investigator |4 oth | |
| 700 | 1 | |a Pestronk, Alan |e investigator |4 oth | |
| 700 | 1 | |a Renfoe, James B |e investigator |4 oth | |
| 700 | 1 | |a Russman, Barry S |e investigator |4 oth | |
| 700 | 1 | |a Smith, Edward C |e investigator |4 oth | |
| 700 | 1 | |a So, Yuen T |e investigator |4 oth | |
| 700 | 1 | |a Wang, Ching H |e investigator |4 oth | |
| 700 | 1 | |a Day, John W |e investigator |4 oth | |
| 700 | 1 | |a Sproule, Douglas M |e investigator |4 oth | |
| 700 | 1 | |a Wagner, Kathryn R |e investigator |4 oth | |
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