A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy
© 2021 Wiley Periodicals LLC..
INTRODUCTION/AIMS: In this study we report the results of a phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab, a myostatin inhibitor, in patients with fukutin-related protein (FKRP)-associated limb-girdle muscular dystrophy.
METHODS: Nineteen patients were enrolled and assigned to one of three dosing arms (5, 20, or 40 mg/kg every 4 weeks). After 32 weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40 mg/kg) for an additional 32 weeks. An extension study was also conducted. The primary endpoints were safety and tolerability. Secondary endpoints included muscle strength, timed function testing, pulmonary function, lean body mass, pharmacokinetics, and pharmacodynamics. As an exploratory outcome, muscle fat fractions were derived from whole-body magnetic resonance images.
RESULTS: Serum concentrations of domagrozumab increased in a dose-dependent manner and modest levels of myostatin inhibition were observed in both serum and muscle tissue. The most frequently occurring adverse events were injuries secondary to falls. There were no significant between-group differences in the strength, functional, or imaging outcomes studied.
DISCUSSION: We conclude that, although domagrozumab was safe in patients in limb-girdle muscular dystrophy type 2I/R9, there was no clear evidence supporting its efficacy in improving muscle strength or function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
Muscle & nerve - 64(2021), 2 vom: 07. Aug., Seite 172-179 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Leung, Doris G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.09.2021 Date Revised 06.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/mus.27259 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325131333 |
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| 100 | 1 | |a Leung, Doris G |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 06.09.2021 | ||
| 500 | |a Date Revised 06.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Wiley Periodicals LLC. | ||
| 520 | |a INTRODUCTION/AIMS: In this study we report the results of a phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab, a myostatin inhibitor, in patients with fukutin-related protein (FKRP)-associated limb-girdle muscular dystrophy | ||
| 520 | |a METHODS: Nineteen patients were enrolled and assigned to one of three dosing arms (5, 20, or 40 mg/kg every 4 weeks). After 32 weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40 mg/kg) for an additional 32 weeks. An extension study was also conducted. The primary endpoints were safety and tolerability. Secondary endpoints included muscle strength, timed function testing, pulmonary function, lean body mass, pharmacokinetics, and pharmacodynamics. As an exploratory outcome, muscle fat fractions were derived from whole-body magnetic resonance images | ||
| 520 | |a RESULTS: Serum concentrations of domagrozumab increased in a dose-dependent manner and modest levels of myostatin inhibition were observed in both serum and muscle tissue. The most frequently occurring adverse events were injuries secondary to falls. There were no significant between-group differences in the strength, functional, or imaging outcomes studied | ||
| 520 | |a DISCUSSION: We conclude that, although domagrozumab was safe in patients in limb-girdle muscular dystrophy type 2I/R9, there was no clear evidence supporting its efficacy in improving muscle strength or function | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a FKRP | |
| 650 | 4 | |a clinical trial | |
| 650 | 4 | |a domagrozumab | |
| 650 | 4 | |a limb-girdle muscular dystrophy | |
| 650 | 4 | |a myostatin inhibition | |
| 650 | 4 | |a whole-body MRI | |
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| 650 | 7 | |a domagrozumab |2 NLM | |
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| 700 | 1 | |a Ahlawat, Shivani |e verfasserin |4 aut | |
| 700 | 1 | |a Jacobs, Michael A |e verfasserin |4 aut | |
| 700 | 1 | |a Parekh, Vishwa S |e verfasserin |4 aut | |
| 700 | 1 | |a Braverman, Vladimir |e verfasserin |4 aut | |
| 700 | 1 | |a Summerton, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Mansour, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Stinson, Nikia |e verfasserin |4 aut | |
| 700 | 1 | |a Bibat, Genila |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Carl |e verfasserin |4 aut | |
| 700 | 1 | |a Marraffino, Shannon |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Kathryn R |e verfasserin |4 aut | |
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