Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease

J Pediatr. 2010 May;156(5):832-7, 837.e1. doi: 10.1016/j.jpeds.2009.11.007. Epub 2010 Jan 25.

Abstract

Objectives: To investigate a 4-year prospective clinical trial of agalsidase alfa in children with Fabry disease, an X-linked metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A.

Study design: Seventeen (16 boys, 1 girl; age range, 7.3 to 18.4 years) of the 24 children who completed a 6-month, open-label agalsidase alfa study enrolled in a 3.5-year extension study that investigated the safety and potential efficacy of long-term treatment. All 17 patients completed the initial 6-month study, and 10 patients (9 boys) completed the extension study.

Results: Agalsidase alfa was well tolerated. In treated boys, there were sustained, statistically-significant improvements in the clinical features of Fabry disease, including reduced plasma globotriaosylceramide levels, reduced pain severity assessed by the Brief Pain Index, and improved heart rate variability. Mean urine globotriaosylceramide levels were reduced to normal range (P < .05 compared with baseline during 1.5 to 4 years). Kidney function and left ventricular mass indexed to height remained stable throughout.

Conclusions: This clinical trial demonstrates that treatment with agalsidase alfa was well tolerated and associated with improvement of Fabry disease-related features.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adolescent
  • Body Size
  • Child
  • Fabry Disease / drug therapy*
  • Fabry Disease / metabolism
  • Fabry Disease / physiopathology
  • Female
  • Humans
  • Isoenzymes / adverse effects
  • Isoenzymes / therapeutic use
  • Kidney / physiopathology
  • Male
  • Pain Measurement
  • Recombinant Proteins
  • Sweat / physiology
  • Trihexosylceramides / blood
  • Trihexosylceramides / urine
  • Ventricular Function, Left
  • alpha-Galactosidase / adverse effects
  • alpha-Galactosidase / therapeutic use*

Substances

  • Isoenzymes
  • Recombinant Proteins
  • Trihexosylceramides
  • agalsidase alfa
  • globotriaosylceramide
  • alpha-Galactosidase