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.
RCT Entities:
OBJECTIVE: The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant humanarylsulfatase 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.
Authors: Roberto Giugliani; Christina Lampe; Nathalie Guffon; David Ketteridge; Elisa Leão-Teles; James E Wraith; Simon A Jones; Cheri Piscia-Nichols; Ping Lin; Adrian Quartel; Paul Harmatz Journal: Am J Med Genet A Date: 2014-04-24 Impact factor: 2.802
Authors: Shih-Hsin Kan; Mika Aoyagi-Scharber; Steven Q Le; Jon Vincelette; Kazuhiro Ohmi; Sherry Bullens; Daniel J Wendt; Terri M Christianson; Pascale M N Tiger; Jillian R Brown; Roger Lawrence; Bryan K Yip; John Holtzinger; Anil Bagri; Danielle Crippen-Harmon; Kristen N Vondrak; Zhi Chen; Chuck M Hague; Josh C Woloszynek; Diana S Cheung; Katherine A Webster; Evan G Adintori; Melanie J Lo; Wesley Wong; Paul A Fitzpatrick; Jonathan H LeBowitz; Brett E Crawford; Stuart Bunting; Patricia I Dickson; Elizabeth F Neufeld Journal: Proc Natl Acad Sci U S A Date: 2014-09-29 Impact factor: 11.205
Authors: F Santamaria; M V Andreucci; G Parenti; M Polverino; D Viggiano; S Montella; A Cesaro; R Ciccarelli; B Capaldo; G Andria Journal: J Inherit Metab Dis Date: 2007-06-14 Impact factor: 4.982