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

NCT04143958 | Withdrawn Phase 4 FDA Drug

• 3 other identifiers: LPS159182019-000064-21U1111-1223-5105
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Change in Plasma globotriaosylsphingosine (lyso-GL3) level

  Change from baseline to 12 months (week 52) for plasma lyso-GL3 level

  Baseline, 12 months (week 52)

Secondary Outcomes (6)

• Change in GL3 content in podocytes

  Baseline, 12 months (week 52)

• Change in GL3 content in endothelial skin cells

  Baseline, 12 months (week 52)

• Change in measured glomerular filtration rate (mGFR)

  Baseline, 12 months (week 52)

• Change in estimated glomerular filtration rate (eGFR) calculated

  Baseline, 12 months (week 52)

• Change in Mainz Severity Score Index (MSSI) total score

  Baseline, 12 months (week 52)

Study Arms (2)

agalsidase beta

EXPERIMENTAL

Commercially available agalsidase beta treatment at approved dose and regimen;administered once every 2 weeks as an IV infusion

Drug: agalsidase beta (GZ419828)

agalsidase alfa

ACTIVE COMPARATOR

Commercially available agalsidase alfa treatment at approved dose and regimen; administered once every 2 weeks as an IV infusion

Drug: agalsidase alfa

Interventions

agalsidase beta (GZ419828) DRUG

Pharmaceutical form:Powder for concentrate for solution for infusion Route of administration: Intravenous (IV) infusion,

agalsidase beta

agalsidase alfa DRUG

Pharmaceutical form:concentrate for solution for infusion Route of administration: Intravenous (IV) infusion

agalsidase alfa

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 α-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 as measured by 2 separate, morning, clean-catch urine samples taken a few days apart demonstrating an averaged urine protein-creatinine ratio of \<0.5 (ie, \<500 mg protein per 1 g creatinine) between the 2 samples. For participants on angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), the criterion is to be met both prior and after a temporary interruption of ACEIs/ARBs for 4 weeks.
• Participants with plasma lyso-GL3 levels \>20 ng/mL on 2 consecutive samples taken at least 4 weeks apart.
• Participant's medical records (including eGFR values) available and accessible during the study period.
• Participant and/or participant's legal representative has given signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For potential participants age 16 to 18 years, a parent or legal representative is required to sign the ICF, and the potential participant is also required to sign an informed assent form.

You may not qualify if:

• Participants with severe renal impairment (end-stage renal disease, dialysis, or renal transplantation) and/or nephropathies (including diabetic).
• Participants with rapid renal decline: Loss of \>6mL/min/1.73 m\^2 at screening compared to the most recent eGFR value approximately 12 months prior to screening.
• Participants with advanced cardiac failure (Stage D).
• Participants with bleeding disorder, prior history of unexplained bleeding episodes, or receiving mandatory anticoagulants or antiplatelets for any indication not allowing interruption of therapy for renal biopsy.
• Participants with diagnosed diabetes.
• Participants with history of anaphylaxis to Enzyme Replacement Therapy (ERT).
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
• Participants treated for more than 5 years with agalsidase alfa at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) prior to randomization.
• Exposure to migalastat or any investigational study intervention, except agalsidase alfa, for Fabry disease in the last 5 years prior to study participation. Patients who previously participated in any agalsidase alfa clinical study will be eligible if they meet other criteria.
• Exposure to any investigational drugs in the last 4 weeks or 5 half-lives, whichever is longer, prior to screening visit or concomitant enrollment in any other clinical study involving an investigational study treatment.
• Individuals accommodated in an institution because of regulatory or legal order; prisoners or subjects who are legally institutionalized.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
• Participants are dependent on the Sponsor or Investigator or deemed vulnerable for any reason (in conjunction with Section 1.61 of the International Council for Harmonisation Good Clinical Practice \[ICH-GCP\] Ordinance E6).
• Participants who are employees of the clinical study center or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.
• Any specific situation during study implementation/course that may raise ethics consideration

Sponsors & Collaborators

• Sanofi: lead

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase beta; agalsidase alfa

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: October 30, 2019
• Study Start: September 1, 2020
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: April 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share