@article{https://doi.org/10.1002/mus.27259,
author = {Leung, Doris G. and Bocchieri, Alex E. and Ahlawat, Shivani and Jacobs, Michael A. and Parekh, Vishwa S. and Braverman, Vladimir and Summerton, Katherine and Mansour, Jennifer and Stinson, Nikia and Bibat, Genila and Morris, Carl and Marraffino, Shannon and Wagner, Kathryn R.},
title = {A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy},
journal = {Muscle \& Nerve},
volume = {64},
number = {2},
pages = {172-179},
keywords = {clinical trial, domagrozumab, FKRP, limb-girdle muscular dystrophy, myostatin inhibition, whole-body MRI},
doi = {https://doi.org/10.1002/mus.27259},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.27259},
eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/mus.27259},
abstract = {Abstract 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.},
year = {2021}
}