Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy
Open accessAbstract
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 identifiers: NCT02310763 and NCT02907619.
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Other inhibitors of the myostatin/activin pathway have shown increases in lean mass across different populations, including Duchenne muscular dystrophy.
“Other inhibitors of the myostatin/activin pathway (e.g. trevogrumab, domagrozumab, landogrozumab) have shown increases in lean mass across different populations, including Duchenne muscular dystrophy, but strength and function results are inconsistent [68].”
From Muscle loss and GLP-1R agonists use (2025) · cites this paper as [68]
For other myostatin/activin pathway inhibitors, strength and function results are inconsistent.
“Other inhibitors of the myostatin/activin pathway (e.g. trevogrumab, domagrozumab, landogrozumab) have shown increases in lean mass across different populations, including Duchenne muscular dystrophy, but strength and function results are inconsistent [68].”
From Muscle loss and GLP-1R agonists use (2025) · cites this paper as [68]
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“Other inhibitors of the myostatin/activin pathway (e.g. trevogrumab, domagrozumab, landogrozumab) have shown increases in lean mass across different populations, includ - ing Duchenne muscular dystrophy, but strength and function results are inconsistent [68].”
- Authors
- 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., Palmer, J. P., Binks, M., Charnas, L., Marraffino, S., & Wong, B. L.
- Affiliations
- Kennedy Krieger Institute (US)
- University of Pittsburgh (US)
- University of Calgary (CA)
- Western University (CA)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Hyogo Medical University (JP)
- Lawson Health Research Institute (CA)
- University of Minnesota (US)
- University of Utah (US)
- Università Cattolica del Sacro Cuore (IT)
- Istituto Giannina Gaslini (IT)
- Bambino Gesù Children's Hospital (IT)
- Cincinnati Children's Hospital Medical Center (US)
- Pfizer (United States) (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Wagner, Kathryn R.
- ORCID
- Venue
- Neuromuscular Disorders
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 30
- Issue
- 6
- Pages
- 492-502
- ISSN
- 0960-8966 (ISSN-L)
- OpenAlex
- W3028584612
- Cited by
- 67
- References
- 49
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 2
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-02-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuromuscular Disorders (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (submittedVersion, cc-by-nc-nd)
- Scholarship@Western (Western University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Duchenne muscular dystrophy, anti-CD14 antibody, functional outcome, drug safety and tolerability, pharmacokinetics, muscle volume, open-label extension
- MeSH terms
- Adolescent, Child, Exercise Test, Humans, Male, Outcome Assessment, Health Care, Treatment Failure, Muscular Dystrophy, Duchenne, Myostatin, Antibodies, Monoclonal, Humanized
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