Skip to main content

Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.

Publication ,  Journal Article
Clemens, PR; Rao, VK; Connolly, AM; Harper, AD; Mah, JK; Smith, EC; McDonald, CM; Zaidman, CM; Morgenroth, LP; Osaki, H; Satou, Y; Hoffman, EP ...
Published in: JAMA neurology
August 2020

An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.This phase 2 study was a 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period of patients aged 4 to 9 years with DMD amenable to exon 53 skipping. To enroll 16 participants, with 8 participants in each of the 2 dose cohorts, 17 participants were screened. Study enrollment occurred between December 16, 2016, and August 17, 2017, at sites in the US and Canada. Data were collected from December 2016 to February 2018, and data were analyzed from April 2018 to May 2019.Participants received 40 mg/kg (low dose) or 80 mg/kg (high dose) of viltolarsen administered by weekly intravenous infusion.Primary outcomes of the trial included safety, tolerability, and de novo dystrophin protein production measured by Western blot in participants' biceps muscles. Secondary outcomes included additional assessments of dystrophin mRNA and protein production as well as clinical muscle strength and function.Of the 16 included boys with DMD, 15 (94%) were white, and the mean (SD) age was 7.4 (1.8) years. After 20 to 24 weeks of treatment, significant drug-induced dystrophin production was seen in both viltolarsen dose cohorts (40 mg/kg per week: mean [range] 5.7% [3.2-10.3] of normal; 80 mg/kg per week: mean [range] 5.9% [1.1-14.4] of normal). Viltolarsen was well tolerated; no treatment-emergent adverse events required dose reduction, interruption, or discontinuation of the study drug. No serious adverse events or deaths occurred during the study. Compared with 65 age-matched and treatment-matched natural history controls, all 16 participants treated with viltolarsen showed significant improvements in timed function tests from baseline, including time to stand from supine (viltolarsen: -0.19 s; control: 0.66 s), time to run/walk 10 m (viltolarsen: 0.23 m/s; control: -0.04 m/s), and 6-minute walk test (viltolarsen: 28.9 m; control: -65.3 m) at the week 25 visit.Systemic treatment of participants with DMD with viltolarsen induced de novo dystrophin production, and clinical improvement of timed function tests was observed.ClinicalTrials.gov Identifier: NCT02740972.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

JAMA neurology

DOI

EISSN

2168-6157

ISSN

2168-6149

Publication Date

August 2020

Volume

77

Issue

8

Start / End Page

982 / 991

Related Subject Headings

  • Outcome Assessment, Health Care
  • Oligonucleotides, Antisense
  • Oligonucleotides
  • Muscular Dystrophy, Duchenne
  • Male
  • Humans
  • Exons
  • Dystrophin
  • Double-Blind Method
  • Child, Preschool
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Clemens, P. R., Rao, V. K., Connolly, A. M., Harper, A. D., Mah, J. K., Smith, E. C., … CINRG DNHS Investigators, . (2020). Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial. JAMA Neurology, 77(8), 982–991. https://doi.org/10.1001/jamaneurol.2020.1264
Clemens, Paula R., Vamshi K. Rao, Anne M. Connolly, Amy D. Harper, Jean K. Mah, Edward C. Smith, Craig M. McDonald, et al. “Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.JAMA Neurology 77, no. 8 (August 2020): 982–91. https://doi.org/10.1001/jamaneurol.2020.1264.
Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, et al. Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial. JAMA neurology. 2020 Aug;77(8):982–91.
Clemens, Paula R., et al. “Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.JAMA Neurology, vol. 77, no. 8, Aug. 2020, pp. 982–91. Epmc, doi:10.1001/jamaneurol.2020.1264.
Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, McDonald CM, Zaidman CM, Morgenroth LP, Osaki H, Satou Y, Yamashita T, Hoffman EP, CINRG DNHS Investigators. Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial. JAMA neurology. 2020 Aug;77(8):982–991.

Published In

JAMA neurology

DOI

EISSN

2168-6157

ISSN

2168-6149

Publication Date

August 2020

Volume

77

Issue

8

Start / End Page

982 / 991

Related Subject Headings

  • Outcome Assessment, Health Care
  • Oligonucleotides, Antisense
  • Oligonucleotides
  • Muscular Dystrophy, Duchenne
  • Male
  • Humans
  • Exons
  • Dystrophin
  • Double-Blind Method
  • Child, Preschool