To Assess the Glycosphingolipid Clearance and Clinical Effects of Switching to Agalsidase Beta (Fabrazyme) Versus Continuing on Agalsidase Alfa (Replagal) in Male Patients With Classic Fabry Disease

Phase 4

Withdrawn

• Conditions: Fabry Disease
• Interventions: Drug: agalsidase beta (GZ419828); Drug: agalsidase alfa

• Registration Number: NCT04143958
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

To assess reduction of plasma lyso-GL3 level after switch to agalsidase beta from agalsidase alfa

Secondary Objectives:

* 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

Detailed Description

The study will have a screening period of up to 9 weeks. Eligible participants will be randomized to switch to agalsidase beta or to continue agalsidase alfa in a 1:1 ratio for a period of 12 months (52 weeks).

Study Timeline

• Study First Submitted: 2019-10-28
• Study First Submitted QC: 2019-10-28
• Study First Posted: 2019-10-30
• Study Start: 2020-09
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-05
• Last Update Posted: 2023-04-07
• Primary Completion: 2023-11
• Study Completion: 2023-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
agalsidase beta	agalsidase beta (GZ419828)	Commercially available agalsidase beta treatment at approved dose and regimen;administered once every 2 weeks as an IV infusion
agalsidase alfa	agalsidase alfa	Commercially available agalsidase alfa treatment at approved dose and regimen; administered once every 2 weeks as an IV infusion

Primary Outcome Measures

Name	Time	Method
Change in Plasma globotriaosylsphingosine (lyso-GL3) level	Baseline, 12 months (week 52)	Change from baseline to 12 months (week 52) for plasma lyso-GL3 level

Secondary Outcome Measures

Name	Time	Method
Change in GL3 content in podocytes	Baseline, 12 months (week 52)	Change from baseline to 12 months (week 52) for GL3 content in podocytes
Change in GL3 content in endothelial skin cells	Baseline, 12 months (week 52)	Change from baseline to 12 months (Week 52) for GL3 content in endothelial skin cells
Change in measured glomerular filtration rate (mGFR)	Baseline, 12 months (week 52)	Change from baseline to 12 months (Week 52) for measured glomerular filtration rate (mGFR) (measured by iohexol clearance)
Change in estimated glomerular filtration rate (eGFR) calculated	Baseline, 12 months (week 52)	Change from baseline to 12 months (Week 52) for estimated glomerular filtration rate (eGFR) calculated using age appropriate formula \[Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)/ Bedside-Schwartz\]
Change in Mainz Severity Score Index (MSSI) total score	Baseline, 12 months (week 52)	Change from baseline to 12 months (Week 52) for Mainz Severity Score Index (MSSI), based on MSSI total score
Change in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score	Baseline, 12 months (week 52)	Change from baseline to 12 months (Week 52) in Fabry Disease Patient Reported Outcomes (FD-PRO) score, based on FD-PRO total symptom score