title: A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).
abstract: OBJECTIVE
  To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.
  
  
  METHODS
  Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline.
  
  
  RESULTS
  Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study.
  
  
  CONCLUSIONS
  This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.
authors.affiliation: University of North Carolina, Department of Pediatrics, Chapel Hill, NC 27599, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Muenzer
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.forename: Ashok
authors.initials: A
authors.lastname: Vellodi
authors.forename: Rick
authors.initials: R
authors.lastname: Martin
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
authors.forename: Muge
authors.initials: M
authors.lastname: Gucsavas-Calikoglu
authors.forename: Suresh
authors.initials: S
authors.lastname: Vijayaraghavan
authors.forename: Susanne
authors.initials: S
authors.lastname: Wendt
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wendt
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Puga
authors.forename: Antonio
authors.initials: A
authors.lastname: Puga
authors.forename: Brian
authors.initials: B
authors.lastname: Ulbrich
authors.forename: Marwan
authors.initials: M
authors.lastname: Shinawi
authors.forename: Maureen
authors.initials: M
authors.lastname: Cleary
authors.forename: Diane
authors.initials: D
authors.lastname: Piper
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Conway
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Conway
authors.forename: Alan
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004361:Drug Tolerance; D006023:Glycoproteins / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007066:Iduronate Sulfatase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D006023:Glycoproteins; C018322:IDS protein, human; D011994:Recombinant Proteins; D007066:Iduronate Sulfatase