Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy

Craig M McDonald, Brenda Wong, Kevin M. Flanigan, Rosamund Wilson, Sjef de Kimpe, Afrodite Lourbakos, Zhengning Lin, Erik K Henricson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAnnals of Clinical and Translational Neurology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Duchenne Muscular Dystrophy
Placebos
Walking
PRO051
Respiratory Function Tests
Muscle Strength
Proteinuria
Half-Life
Therapeutics
Pharmacokinetics
Safety
Injections

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. / McDonald, Craig M; Wong, Brenda; Flanigan, Kevin M.; Wilson, Rosamund; de Kimpe, Sjef; Lourbakos, Afrodite; Lin, Zhengning; Henricson, Erik K.

In: Annals of Clinical and Translational Neurology, 01.01.2018.

Research output: Contribution to journalArticle

McDonald, Craig M ; Wong, Brenda ; Flanigan, Kevin M. ; Wilson, Rosamund ; de Kimpe, Sjef ; Lourbakos, Afrodite ; Lin, Zhengning ; Henricson, Erik K. / Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. In: Annals of Clinical and Translational Neurology. 2018.
@article{0f3f9ace9ca8477ebab86e2cd68c913b,
title = "Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy",
abstract = "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.",
author = "McDonald, {Craig M} and Brenda Wong and Flanigan, {Kevin M.} and Rosamund Wilson and {de Kimpe}, Sjef and Afrodite Lourbakos and Zhengning Lin and Henricson, {Erik K}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/acn3.579",
language = "English (US)",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy

AU - McDonald, Craig M

AU - Wong, Brenda

AU - Flanigan, Kevin M.

AU - Wilson, Rosamund

AU - de Kimpe, Sjef

AU - Lourbakos, Afrodite

AU - Lin, Zhengning

AU - Henricson, Erik K

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85050601959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050601959&partnerID=8YFLogxK

U2 - 10.1002/acn3.579

DO - 10.1002/acn3.579

M3 - Article

AN - SCOPUS:85050601959

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

ER -