Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy

Kathryn R. Wagner; Hoda Z. Abdel-Hamid; Jean K. Mah; Craig Campbell; Michela Guglieri; Francesco Muntoni; Yasuhiro Takeshima; Craig M. McDonald; Anna Kostera-Pruszczyk; Peter Karachunski; Russell J. Butterfield; Eugenio Mercuri; Chiara Fiorillo; Enrico S. Bertini; Cuixia Tian; Jeffery Statland; Alesia B. Sadosky; Vivek S. Purohit; Sarah P. Sherlock; Jeffrey P. Palmer; Michael Binks; Lawrence Charnas; Shannon Marraffino; Brenda L. Wong

doi:10.1016/j.nmd.2020.05.002

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy

Kathryn R. Wagner, Hoda Z. Abdel-Hamid, Jean K. Mah, Craig Campbell, Michela Guglieri, Francesco Muntoni, Yasuhiro Takeshima, Craig M. McDonald, Anna Kostera-Pruszczyk, Peter Karachunski, Russell J. Butterfield, Eugenio Mercuri, Chiara Fiorillo, Enrico S. Bertini, Cuixia Tian, Jeffery Statland, Alesia B. Sadosky, Vivek S. Purohit, Sarah P. Sherlock, Jeffrey P. PalmerMichael Binks, Lawrence Charnas, Shannon Marraffino, Brenda L. Wong

Neurology

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Abstract

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (–7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov

Original language	English (US)
Pages (from-to)	492-502
Number of pages	11
Journal	Neuromuscular Disorders
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.nmd.2020.05.002
State	Published - Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

4-stair climb
Duchenne muscular dystrophy
domagrozumab
myostatin inhibitor

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Wagner, K. R., Abdel-Hamid, H. Z., Mah, J. K., Campbell, C., Guglieri, M., Muntoni, F., Takeshima, Y., McDonald, C. M., Kostera-Pruszczyk, A., Karachunski, P., Butterfield, R. J., Mercuri, E., Fiorillo, C., Bertini, E. S., Tian, C., Statland, J., Sadosky, A. B., Purohit, V. S., Sherlock, S. P., ... Wong, B. L. (2020). Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscular Disorders, 30(6), 492-502. https://doi.org/10.1016/j.nmd.2020.05.002

Wagner, KR, Abdel-Hamid, HZ, Mah, JK, Campbell, C, Guglieri, M, Muntoni, F, Takeshima, Y, McDonald, CM, Kostera-Pruszczyk, A, Karachunski, P, Butterfield, RJ, Mercuri, E, Fiorillo, C, Bertini, ES, Tian, C, Statland, J, Sadosky, AB, Purohit, VS, Sherlock, SP, Palmer, JP, Binks, M, Charnas, L, Marraffino, S & Wong, BL 2020, 'Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy', Neuromuscular Disorders, vol. 30, no. 6, pp. 492-502. https://doi.org/10.1016/j.nmd.2020.05.002

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abstract = "We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (–7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov",

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AU - Wagner, Kathryn R.

AU - Abdel-Hamid, Hoda Z.

AU - Mah, Jean K.

AU - Campbell, Craig

AU - Guglieri, Michela

AU - Muntoni, Francesco

AU - Takeshima, Yasuhiro

AU - McDonald, Craig M.

AU - Kostera-Pruszczyk, Anna

AU - Karachunski, Peter

AU - Butterfield, Russell J.

AU - Mercuri, Eugenio

AU - Fiorillo, Chiara

AU - Bertini, Enrico S.

AU - Tian, Cuixia

AU - Statland, Jeffery

AU - Sadosky, Alesia B.

AU - Purohit, Vivek S.

AU - Sherlock, Sarah P.

AU - Palmer, Jeffrey P.

AU - Binks, Michael

AU - Charnas, Lawrence

AU - Marraffino, Shannon

AU - Wong, Brenda L.

PY - 2020/6

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N2 - We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (–7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov

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Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy

Abstract

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