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A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy.

Author information

Affiliations

  • 1. Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, Maryland, USA.
      Authors
    • Leung DG 1
    • Summerton K 1
    • Stinson N 1
    • Bibat G 1
    • Wagner KR 1
    (5 authors)
  • 2. Department of Computer Science, Johns Hopkins University, Baltimore, Maryland, USA.
      Authors
    • Bocchieri AE 2
    • Parekh VS 2
    • Braverman V 2
    (3 authors)
  • 3. Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
      Authors
    • Ahlawat S 3
    • Jacobs MA 3
    (2 authors)
  • 4. Tulane University School of Medicine, New Orleans, Louisiana, USA.
      Authors
    • Mansour J 4
    (1 author)
  • 5. Solid Biosciences, Cambridge, Massachusetts, USA.
      Authors
    • Morris C 5
    (1 author)
    • Show all (6)

ORCIDs linked to this article

Muscle & Nerve, 24 May 2021, 64(2):172-179
https://doi.org/10.1002/mus.27259 PMID: 33961310 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1002/mus.27259

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Funding 

Funders who supported this work.

Limb Girdle Muscular Dystrophy 2i Research Fund

    NINDS NIH HHS (1)

    Pfizer