A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease

• To evaluate the efficacy of Fabrazyme [agalsidase beta (recombinant form)] in reducing interventricular septum and left ventricular posterior wall thickness assessed by echocardiogram [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
• To evaluate the efficacy of Fabrazyme [agalsidase beta (recombinant form)] in reducing left ventricular mass (LVM) assessed by echocardiogram [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]

• - To evaluate the efficacy of Fabrazyme in reducing interventricular septum and left ventricular posterior wall thickness assessed by echocardiogram
• - To evaluate the efficacy of Fabrazyme in reducing left ventricular mass (LVM) assessed by echocardiogram.

• Results of overall evaluation of changes in cardiac function assessed by tests (echocardiogram,cardiac catheterization(optional),electrocardiogram,BNP), clinical symptoms(subjective symptoms) and the NYHA cardiac functional classification [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
• To evaluate in evaluable subjects the efficacy of this drug in reducing GL-3 accumulation in myocardial tissue [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
• To evaluate the efficacy of this drug according to SF-36 Health Survey scores [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
• To evaluate the safety of this drug [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]

• - To make an overall evaluation of changes in cardiac function assessment by cardiac function tests (echocardiogram, cardiac catheterization, electrocardiogram, BNP), clinical symptoms (subjective symptoms) and the NYHA cardiac functional classification.
• - To evaluate the efficacy of this drug in lowering plasma globotriaosylceramide (hereinafter referred to as GL-3) level.
• - To evaluate in evaluable subjects the efficacy of this drug in reducing GL-3 accumulation in myocardial tissue.
• - To evaluate the efficacy of this drug according to SF-36 Health Survey scores.
• - To evaluate the safety of this drug.

This is a multi-center, open label, phase IV study conducted to evaluate the efficacy and safety of Fabrazyme [agalsidase beta (recombinant form)] administered by intravenous drip infusion in patients with cardiac Fabry disease.

Patients will participate for 4 weeks or less in the baseline period and 156 weeks for the treatment period.

Inclusion Criteria:

• Patients definitively diagnosed with cardiac Fabry disease (who fulfill all of the following criteria):

  • In the case of male patients, documented plasma or leukocyte a- GAL activity is no more than 20% of normal value (except for heterozygous female patients.)
  • Left ventricular hypertrophy is noted.
  • Accumulation of GL-3 in the myocardium or a genetic deficiency associated with a-GAL has been confirmed
  • Or in the case of heterozygous female patients, when the family (father or son) is diagnosed with Fabry disease. (Father or son is related by birth.)
  • Without symptoms or signs of Fabry, such as
  • acroparesthesia
  • angiokeratomas
  • abnormal sweating
  • pain of distal extremities
  • chronic abdominal pain/diarrhea and corneal opacities are observed, except for proteinuria sign.
• Patient with interventricular and posterior wall thickness of at least 13 mm on echocardiography within 3 months before signed date to informed consent
• Patients in whom cardiac function is rated as Class I or II according to the NYHA classification when giving informed consent.
• Patient classification: inpatients and outpatients
• Patients who have given written informed consent before the study-related baseline tests.

Exclusion Criteria:

• Patient with severe hypertension (e.g., systolic blood pressure 180 mmHg and/or diastolic blood pressure 110 mmHg in spite of adequate medication)
• Patients whose serum creatinine level is higher than the upper normal limit within 3 months (12 weeks) prior to giving informed consent.
• Patients who have undergone kidney transplantation or are currently on dialysis.
• Patients with any serious hepatic disorder. Patients who have abnormal hepatic function test values within 3 months (12 weeks) prior to giving informed consent (when either ALT or AST level exceeds the value five times as high as the upper normal limit).
• Permanent pacemaker or defibrillator implanted patients
• Pregnant or lactating women
• Patients who have taken this drug for 6 months (26 weeks) or more before giving informed consent.
• Patients who have participated in a clinical study employing any other investigational product within 3 months prior to giving informed consent.
• Enzyme replacement therapy history, except for Fabrazyme [agalsidase beta (recombinant form)].
• Patients who are unwilling to comply with the requirements of the protocol.
• Others judged by the investigator or sub-investigator to be ineligible for the study