Original articleEnzyme 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
Section snippets
Study Design
This was a randomized, double-blind, multicenter, placebo-controlled, 24-week Phase 3 study of rhASB followed by a 24-week extension period. Following screening eligibility assessments, eligible patients completed baseline assessments, and they were randomized in a 1:1 ratio to receive weekly intravenous infusions of either rhASB 1.0 mg/kg or placebo solution for 24 consecutive weeks. After 24 weeks, all patients completing treatment were enrolled in the open-label extension. The investigator
Characteristics of Patients
Characteristics of the study patients are shown in Table I. Although those in the placebo group were, on average, younger, shorter, and weighed less than those in the rhASB group, none of these differences was statistically significant. All 28 eligible patients were randomized, as were 11 patients who did not fulfill inclusion criteria. Seven of these exceeded the walk distance eligibility entry criteria at screening, 3 were <7 years of age, and 1 had experienced a failed bone marrow transplant
Discussion
Mucopolysaccharidosis VI is a rare, fatal lysosomal storage disease with no effective treatment. Administration of 1.0 mg/kg rhASB led to a statistically significant improvement in endurance, as measured by the 12MWT and 3MSC; and in a statistically significant decline in urinary GAG excretion. rhASB was well tolerated, with most AEs attributable to manifestations of the MPS VI disease. IARs related to study drug administration were readily managed and did not result in discontinuation of the
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This study was sponsored by BioMarin Pharmaceutical Inc., and it was supported, in part, with funds provided by the National Center for Research Resources, 5 M01 RR-01271 (Dr Harmatz).
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List of the investigators for the MPS VI Phase 3 Study Group is available at www.jpeds.com.
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Drs Harmatz, Wittes, Lowe, Berger, and Yu have provided consulting support to BioMarin Pharmaceutical Inc., Novato, California.
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Drs Swiedler, Kakkis, and Ms Newman are employees and stockholders of BioMarin Pharmaceutical, Inc.