title: Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter syndrome).
abstract: BACKGROUND
  Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase (IDS). In affected patients, glycosaminoglycan (GAG) accumulates in the lysosomes of many organs and tissues contributing to the pathology associated with MPS II. The objective of this phase I/II clinical study was to evaluate the efficacy and safety of recombinant human iduronate-2-sulfatase (idursulfase beta, Hunterase®) in the treatment of MPS II.
  
  
  METHODS
  Thirty-one MPS II patients between 6 and 35 years of age were enrolled in a randomized, single-blinded, active comparator-controlled phase I/II trial for 24 weeks. Patients were randomized to active comparator infusions (N=11), 0.5 mg/kg idursulfase beta infusions (N=10), or 1.0 mg/kg idursulfase beta infusions (N=10). The primary efficacy variable was the level of urinary GAG excretion. The secondary variables were changes in the distance walked in 6 minutes (6-minute walk test, 6MWT), echocardiographic findings, pulmonary function tests, and joint mobility.
  
  
  RESULTS
  Patients in all three groups exhibited reduction in urine GAG and this reduced GAG level was maintained for 24 weeks. Urine GAG was also significantly reduced in the 0.5 mg/kg and 1.0 mg/kg idursulfase beta groups when compared to the active comparator group (P = 0.043, 0.002, respectively). Changes in 6MWT were significantly greater in the 0.5 mg/kg and 1.0 mg/kg idursulfase groups than in the active comparator group (p= 0.003, 0.015, respectively). Both idursulfase beta infusions were generally safe and well tolerated, and elicited no serious adverse drug reactions. The most frequent adverse events were urticaria and skin rash, which were easily controlled with administration of antihistamines.
  
  
  CONCLUSIONS
  This study indicates that idursulfase beta generates clinically significant reduction of urinary GAG, improvements in endurance as measured by 6MWT, and it has an acceptable safety profile for the treatment of MPS II.
authors.affiliation: Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Sohn
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Park
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ah-Ra
authors.initials: AR
authors.lastname: Ko
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kwon
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Han
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004452:Echocardiography; D056947:Enzyme Replacement Therapy; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007066:Iduronate Sulfatase / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D007066:Iduronate Sulfatase; C517982:idursulfase