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 |
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Authors: | Harmatz Paul,Giugliani Roberto,Schwartz Ida,Guffon Nathalie,Teles Elisa Le?o,Miranda M Clara Sá,Wraith J Edmond,Beck Michael,Arash Laila,Scarpa Maurizio,Yu Zi-Fan,Wittes Janet,Berger Kenneth I,Newman Mary S,Lowe Ann M,Kakkis Emil,Swiedler Stuart J MPS VI Phase Study Group |
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Affiliation: | Children's Hospital & Research Center at Oakland, California 94609, USA, and Children's Hospital, University of Mainz, Germany. Pharmatz@mail.cho.org |
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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. |
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Keywords: | AE, Adverse event ASB, N-acetylgalactosamine 4-sulfatase (arylsulfatase B) ERT, Enzyme replacement therapy FVC, Forced vital capacity GAG, Glycosaminoglycan IAR, Infusion-associated reaction MPS, Mucopolysaccharidosis MVV, Maximum voluntary ventilation rhASB, Recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B) ROM, Range of motion 3MSC, 3-minute stair climb 12MWT, 12-minute walk test |
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