Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

J Pediatr. 2006 Apr;148(4):533-539. doi: 10.1016/j.jpeds.2005.12.014.

Abstract

Objective: The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment.

Study design: Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks.

Results: After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein.

Conclusion: rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Child
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Glycosaminoglycans / urine
  • Humans
  • Linear Models
  • Male
  • Mucopolysaccharidosis VI / drug therapy*
  • N-Acetylgalactosamine-4-Sulfatase / therapeutic use*
  • Recombinant Proteins
  • Safety
  • Walking

Substances

  • Glycosaminoglycans
  • Recombinant Proteins
  • N-Acetylgalactosamine-4-Sulfatase