A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: Agalsidase beta; Agalsidase beta
Intervention description: Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks; Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: Male
Minimum age: 5 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: α-GAL, α-Galactosidase-A, r-hαGAL

Summary:

      The purpose of this study was 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) were effective in
      treatment-naïve pediatric participants without severe symptoms. Participants were to be
      treated for 5 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant and/or participant's parent(s)/legal guardian(s) must provide written
             informed assent/consent prior to any protocol-related procedures being performed.

          -  The participant must had a confirmed diagnosis of Fabry disease as documented by
             leukocyte α-Galactosidase A (αGAL) activity of <4 nmol/hr/mg leukocyte (preferred
             assay; resulted from a central laboratory). If the leukocyte αGAL activity assay was
             difficult to obtain, the participant might be enrolled based on documented plasma αGAL
             <1.5 nmol/hr/mL, with the agreement of the Medical Monitor (resulted from a central
             laboratory).

          -  The participant must had 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 participant must be male ≥5 and ≤18 years of age.

        Exclusion Criteria:

          -  Participant had 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).

          -  Participant had 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
             might be acceptable, after consultation with the Medical Monitor.

          -  Participant had documented evidence of stroke or transient ischemic attack (TIA), or
             if a brain magnetic resonance imaging (MRI) had been performed, bright lesions >2 mm
             on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the
             white matter or the basal ganglia.

          -  Participant had severe and recurrent acroparesthesia, judged by the physician as
             frequent (more than once a week) pain episodes for at least 3 months that influenced
             daily activities, irrespective of medication.

          -  Participant had 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.

          -  Participant had received prior treatment specific to Fabry Disease.

          -  Participant had participated in a study employing an investigational drug within 30
             days of the start of their participation in this study.

          -  Participant had any medical condition or extenuating circumstance, which in the
             opinion of the Study Investigator, could interfere with study compliance.

          -  Participant had 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.

          -  Participant was on treatment with angiotensin converting enzyme inhibitors/angiotensin
             receptor blockers (ACEIs/ARBs).

          -  Participant had any contra-indication mentioned in the labeling of Fabrazyme and/or
             iohexol (Omnipaque).

          -  Participant or parent(s)/legal guardian(s) was unwilling to comply with the
             requirements of the protocol.