Agalsidase Beta Long-Term Treatment Outcome for Fabry Disease Patients With IVS4 Mutation in Taiwan

An Observational Study of Enzyme Replacement Therapy-Naïve and Agalsidase Beta-Treated Fabry Disease Patients With GLA IVS4 919 G>A Mutation in Taiwan

This is a national, multicenter, observational, cohort study designed to assess clinical outcomes upon agalsidase beta treatment, to characterize the clinical manifestations, and to collect the natural history on male and female Fabry disease adult patients who carry the GLA IVS4.

This study aims to retrospectively and prospectively investigate the disease natural history, clinical manifestations, and the treatment outcomes upon agalsidase beta in Fabry disease (FD) patients carrying the GLA IVS4 mutation from medical records, physician assessments, and patient-reported outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Fabry Disease

Detailed Description

Study Design Time Perspective: Retrospective and Prospective

• Study Type: Observational
• Enrollment (Actual): 78

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan, 407219
    • Investigational Site Number : 1580004
  • Tainan, Taiwan, 704
    • Investigational Site Number : 1580005
  • Taipei, Taiwan, 100
    • Investigational Site Number : 1580001
  • Taipei, Taiwan, 112
    • Investigational Site Number : 1580002
  • Taipei, Taiwan, 104
    • Investigational Site Number : 1580003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

FD patients carrying the GLA IVS4 mutation, who are eligible for 1 of the cohorts (1, 2, 3).

Description

Inclusion Criteria:

- Provide signed informed consent.

Cohort 1:

• Male or female Fabry disease patient with documented GLA IVS4 in medical record.
• Age ≥ 18 years old at the time of signing informed consent.
• The maximum proportion of female is 20% of cohort 1.
• Patient who has received agalsidase beta treatment for at least 6 months.
• The data of LVMI, LPWT, IVST and blood lyso-Gb3 concentration are all available within 6 months prior to agalsidase beta treatment initiation.

Cohort 2:

• Male or female Fabry disease patient with documented GLA IVS4 in medical record.
• Age ≥ 18 years old at the time of signing informed consent.
• The maximum proportion of female is 20% of cohort 2.
• Patient who plans to apply for the National Health Insurance Reimbursement for agalsidase beta medication.
• The data of LVMI, LPWT, IVST and blood lyso-Gb3 concentration are all available within 6 months prior to agalsidase beta treatment initiation.

Cohort 3:

• Male or female Fabry disease patients with documented GLA IVS4 mutation in medical record.
• Male patient is aged ≥ 30 years old and female patient is aged ≥ 40 years old at the time of signing informed consent.
• The maximum proportion of female is 20% of cohort 3.
• Patient who has never received agalsidase alpha or agalsidase beta treatment (ERT-naïve).
• Elevated blood lyso-Gb3.

• At least ONE of the following conditions documented in medical record:

  1. cardiac parameter abnormalities (e.g. via imaging, electrophysiology, or biomarker);
  2. at least one FD-related sign/symptom.
• The data of LVMI, LPWT, IVST and blood lyso-Gb3 concentration are all available within 6 months.
• Patients who are expected not to receive ERT or FD-specific treatment per investigator's judgement.

Exclusion Criteria:

• Any condition that, in the opinion of the Investigator, may interfere with patient's participation in the study, such as life expectancy of less than 6 months (e.g. diagnosed with malignancy, CAD)
• Fabry patients who have severe heart disease (NYHA Class IV) or severe myocardial fibrosis per investigator judgement
• Known non-Fabry disease infiltrative cardiomyopathy including amyloidosis
• Known non-GLA genetic (e.g., sarcomeric, metabolic mutations) hypertrophic cardiomyopathy.
• Patients who are receiving any Fabry disease-specific treatment (enzyme replacement therapy, chaperone therapy, substrate reduction therapy, or gene therapy) other than agalsidase beta for Fabry disease
• Pregnancy or suspected pregnancy
• Patient diagnosed with moderate to severe dementia
• Unstable patient condition as judged by investigator (e.g., hypertension, diabetes, and systematic disease)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort 1; Patients with Galactosidase Alpha gene (GLA) IVS4 who have already received agalsidase beta treatment
Cohort 2; Patients with GLA IVS4 who will initiate agalsidase beta treatment
Cohort 3; Enzyme replacement therapy (ERT)-naive Fabry disease patients with GLA IVS4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cohort 1: change of Left ventricular mass index (LVMI) as measured by echocardiography in agalsidase beta-treated patients	through study completion with a minimum of 2 years
Cohort 2: change of Left ventricular mass index (LVMI) as measured by echocardiography in agalsidase beta-treated patients	up to 1.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of Left posterior wall thickness (LPWT) as measured by echocardiography	For cohort 1, through study completion with a minimum of 2 years For cohort 2, 1.5 years For cohort 3, through study completion with a minimum of 1.5 years
Change of Interventricular septal thickness (IVST) as measured by echocardiography	For cohort 1, through study completion with a minimum of 2 years For cohort 2, 1.5 years For cohort 3, through study completion with a minimum of 1.5 years
Change of blood Globotriaosylsphingosine (lyso-Gb3) concentration	For cohort 1, through study completion with a minimum of 2 years For cohort 2, 1.5 years For cohort 3, through study completion with a minimum of 1.5 years
Change of left ventricular mass index (LVMI) as measured by echocardiography in ERT-naive patients	For cohort 3, through study completion with a minimum of 1.5 years

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences and Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2023
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): September 10, 2026

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Fabry Disease
• Other Study ID Numbers: OBS17349; U1111-1287-7177 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No