A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).

Abstract

PURPOSE:

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.

CONCLUSION:

This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.

• Authors: Joseph Muenzer, James E Wraith, Michael Beck, Roberto Giugliani, Paul Harmatz, Christine M Eng, Ashok Vellodi, Rick Martin, Uma Ramaswami, Muge Gucsavas-Calikoglu, Suresh Vijayaraghavan, Susanne Wendt, Suzanne Wendt, Ana Cristina Puga, Antonio Puga, Brian Ulbrich, Marwan Shinawi, Maureen Cleary, Diane Piper, Anne Marie Conway, Ann Marie Conway, Alan Kimura
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 8 Issue 8 Pg. 465-73 (Aug 2006) ISSN: 1098-3600 [Print] United States
• PMID: 16912578 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycoproteins
• IDS protein, human
• Recombinant Proteins
• Iduronate Sulfatase

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Double-Blind Method
• Drug Tolerance
• Glycoproteins (adverse effects, therapeutic use)
• Humans
• Iduronate Sulfatase (adverse effects, therapeutic use)
• Male
• Mucopolysaccharidosis II (drug therapy, physiopathology)
• Recombinant Proteins (adverse effects, therapeutic use)
• Safety
• Vital Capacity (drug effects)