A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms (FIELD)

• GL-3 clearance in Plasma [ Time Frame: Up to month 60 ] [ Designated as safety issue: No ]
• GL-3 clearance in Urine [ Time Frame: Up to month 60 ] [ Designated as safety issue: No ]

• GL-3 clearance in Plasma [ Time Frame: throughout study (5 years) ] [ Designated as safety issue: No ]
• GL-3 clearance in Urine [ Time Frame: throughout study (5 years) ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether 2 alternative dosing regimens of Fabrazyme (agalsidase beta) (1.0 mg/kg every 4 weeks or 0.5 mg/kg every 2 weeks) are effective in treatment-naïve pediatric patients without severe symptoms. Patients will be treated for 5 years.

• Biological: agalsidase beta
  1.0 mg/kg/4 weeks
  Other Name: Fabrazyme
• Biological: agalsidase beta
  0.5 mg/kg/2 weeks
  Other Name: Fabrazyme

• Active Comparator: Fabrazyme Dosing Regimen 1
  Intervention: Biological: agalsidase beta
• Active Comparator: Fabrazyme Dosing Regimen 2
  Intervention: Biological: agalsidase beta

Inclusion Criteria:

• The patient and/or patient's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.
• The patient must have a confirmed diagnosis of Fabry disease as documented by leukocyte α-Galactosidase A (αGAL) activity of <4 nmol/hr/mg leukocyte (preferred assay; results from a central laboratory). If the leukocyte αGAL activity assay is difficult to obtain, the patient may be enrolled based on documented plasma αGAL <1.5 nmol/hr/mL, with the agreement of the Medical Monitor (results from a central laboratory).
• The patient must have evidence of globotriaosylceramide (GL-3) accumulation as documented by plasma GL-3 (>7.0 µg/mL) or urinary GL-3 (>0.3 mg GL-3/mmol creatinine) levels (results from a central laboratory).
• The patient must be male ≥5 and ≤18 years of age.

Exclusion Criteria:

• Patient has albuminuria (first morning void urinary albumin/creatinine ratio >30 mg/g on at least 2 out of 3 consecutive samples, each at least 1 week apart).
• Patient has a Glomerular Filtration Rate (GFR) by iohexol <90 L/min/1.73m^2. In case of properly documented low protein intake, values as low as 80 mL/min/1.73 m^2 may be acceptable, after consultation with the Medical Monitor.
• Patient has documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) has been performed, bright lesions >2 mm on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the white matter or the basal ganglia.
• Patient has severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influence daily activities, irrespective of medication.
• Patient has an end-diastolic left ventricular posterior wall thickness (LVPWTd) and/or an end-diastolic interventricular septum thickness (IVSTd)≥2 standard deviations (SD) compared to normal (based on body surface area [BSA] normal ranges from Kampmann, et al 2000) as read at the study site.
• Patient has received prior treatment specific to Fabry Disease.
• Patient has participated in a study employing an investigational drug within 30 days of the start of their participation in this study.
• Patient has any medical condition or extenuating circumstance, which in the opinion of the Study Investigator, could interfere with study compliance.
• Patient has any medical condition or extenuating circumstance, for example diabetes mellitus, which in the opinion of the Study Investigator, could interfere with the interpretation of study results.
• Patient is on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs).
• Patient has any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).
• Patient or parent(s)/legal guardian(s) is unwilling to comply with the requirements of the protocol.