Evaluation of Efficacy and Safety of Agalsidase Beta in Heterozygous Females for Fabry Disease

A Multicenter, Phase 4, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Recombinant Alpha-Galactosidase A (Agalsidase Beta, FABRAZYME) in Heterozygous Females for Fabry Disease

Fabry disease (OMIM 301500) is an X-linked inborn error of sphingolipid metabolism resulting from the deficiency of the lysosomal enzyme alpha-galactosidase A. Heterozygous females for Fabry disease may be symptomatic with cardiac, renal or cerebrovascular involvement. Clearance of Gb3 and stabilization of renal function has been demonstrated in male patients treated with agalsidase beta (FABRAZYME). In contrast, no randomized, controlled study of the efficacy of recombinant alpha-galactosidase A has been reported in heterozygotes for Fabry disease.

The primary objective is to evaluate cardiac left ventricular mass (measured with echocardiography by unique investigator) in females over 15 years of age affected with Fabry disease receiving 70 mg of agalsidase beta every other week, as compared with an untreated controlled group matched for gender and age.

The secondary objectives include evaluation of :

• left ventricular posterior wall thickness (echocardiography)
• interventricular septum thickness (echocardiography)
• tissue doppler imaging (myocardial function)
• EKG
• creatinaemia
• serum cystatin C level
• urinary protein/creatinine ratio
• microalbuminuria
• Gb3 urinary levels

Evaluation of tolerance and safety with :

• Home therapy infusions follow up
• Vitals
• Physical examination
• Adverse events
• Antibodies levels

Inclusion Criteria:

• Female patients over 15 years with clinical and biological evidence of Fabry disease (GLA gene mutation detected)

Exclusion Criteria:

• Pregnancy
• Allergy to agalsidase beta
• Congestive heart failure
• Creatinaemia > 135 µmol/l
• Medical history of stroke during the last year
• Medical history of more than 2 transient ischemic attack
• Blood pressure > 160/95
• Modification in medications treating for blood pressure during the last 3 months before enrollment
• Complete absence of clinical or biological symptoms
• Weight > 87 kg or < 35 kg