A randomized, open-label, active comparator, 2-arm, prospective study to assess the glycosphingolipid clearance and clinical benefits of agalsidase beta (Fabrazyme®) in male patients with classic Fabry disease switching from agalsidase alfa (Replagal®)

INTERVENTION: Trade Name: Fabrazyme Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: AGALSIDASE BETA Current Sponsor code: GZ419828 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5‐ Trade Name: Replagal Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: AGALSIDASE ALFA CAS Number: 104138‐64‐9 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1‐ CONDITION: Fabry's disease ; MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 ‐ Congenital, familial and genetic disorders Therapeutic area: Diseases [C] ‐ Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] PRIMARY OUTCOME: ; Secondary Objective: To assess reduction of kidney podocyte GL3 content after switch to agalsidase beta from agalsidase alfa; ; To assess reduction of GL3 content in endothelial skin cells after switch to agalsidase beta from agalsidase alfa; ; To assess change in renal function after switch to agalsidase beta from agalsidase alfa; ; To assess disease severity and clinical changes after switch to agalsidase beta from agalsidase alfa; ; To assess improvement in symptoms of Fabry disease after switch to agalsidase beta from agalsidase alfa; Main Objective: To assess reduction of plasma lyso‐GL3 level after switch to agalsidase beta from agalsidase alfa Primary end point(s): Change in Plasma globotriaosylsphingosine (lyso‐GL3) level Timepoint(s) of evaluation of this end point: Baseline, 12 months (week 52) SECONDARY OUTCOME: ; Secondary end point(s): 1) Change in GL3 content in podocytes ; ; 2) Change in GL3 content in endothelial skin cells ; ; 3) Change in measured glomerular filtration rate (mGFR) ; ; 4) Change in estimated glomerular filtration rate (eGFR) calculated ; ; 5) Change in Mainz Severity Score Index (MSSI) total score ; ; 6) Change in Fabry Disease Patient Reported Outcomes (FD‐PRO) total symptom score; Timepoint(s) of evaluation of this end point: Timepoint for all secondary end points: Baseline, 12 months (week 52) INCLUSION CRITERIA: Male participant must be 16 to 45 years of age inclusive, at the time of signing the informed consent. Participants who are diagnosed with classic Fabry disease based on phenotype, presence or absence of characteristic Fabry disease symptoms including neuropathic pain, clustered angiokeratoma and/or cornea verticillata, leucocyte a‐GAL A enzyme activity (3% or less compared to control), and genotype (optional). Participants who are currently receiving agalsidase alfa for a minimum of 6 months at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) at baseline. Participants who are naïve to agalsidase beta. Participants with estimated glomerular filtration rate (eGFR) =60 mL/min/1.73 m^2 at screening and baseline. Proteinuria level