Long-term outcomes for adults with Fabry disease on migalastat

A Prospective, Observational Study of Patients With Fabry Disease (US Specific)

This project will see if migalastat (compared with enzyme replacement therapy or no treatment) helps adults with Fabry disease maintain kidney function, stay safe, and improve quality of life over several years.

Quick facts

• Study type: Observational
• Enrollment: 450 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Amicus Therapeutics (Industry-sponsored)
• Locations: 8 sites (Birmingham, Alabama and 7 other locations)
• Trial ID: NCT06906367 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter observational registry enrolling at least 450 people with Fabry disease and following them for up to five years after enrollment. Participants will be grouped by treatment: migalastat (≈250), enzyme replacement therapy (≈100), or never-treated (≈100), and data on kidney function, safety events, and health-related quality of life will be collected. Eligible migalastat participants are adults with amenable GLA variants who are starting or recently started commercial migalastat and have eGFR ≥30 mL/min/1.73 m2, with additional clinical criteria for renal decline or proteinuria applied. The study uses routine clinical visits and registry data rather than assigning treatments, allowing real-world effectiveness and safety signals to be observed.

Who should consider this trial

Good fit: Adults (≥18) with genetically confirmed Fabry disease and amenable GLA variants who are starting or have started commercial migalastat within the prior 24 months and have eGFR ≥30 mL/min/1.73 m2, as well as comparable adults on enzyme replacement or never-treated patients, are ideal candidates.

Not a fit: Patients with non-amenable GLA variants, severe renal impairment (eGFR <30 mL/min/1.73 m2), or those who previously participated in a migalastat clinical trial may not be eligible or likely to benefit from participation.

Why it matters

Potential benefit: If successful, the registry could clarify long-term effectiveness and safety of migalastat versus enzyme replacement or no treatment and help guide treatment choices for patients with amenable GLA variants.

How similar studies have performed: Previous randomized trials and real-world reports have shown clinical benefit of migalastat for patients with amenable mutations, but long-term comparative registry data remain limited.

Eligibility criteria

I. Migalastat-treated patients (Commercial only participants)

1. Patients with Fabry disease 18 years or older with amenable GLA variants who have commenced commercial migalastat treatment within 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment and are still taking migalastat at the time of enrollment, or who are starting migalastat at the time of enrollment, excluding those who participated in a prior migalastat clinical trial
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in annualized rate of decline eGFRCKD-EPI of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (\> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

II. Migalastat-treated patients who are not considered to be in renal decline (Commercial migalastat users only)

1\. Patients with Fabry disease with amenable GLA variants who have been on commercial migalastat regardless of the duration of treatment

III. Migalastat-treated patients (Prior clinical trial participants)

1. Patients with Fabry disease 18 years or older who had commenced treatment with migalastat while in a clinical trial and were exposed to treatment for at least 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment, and who are still taking migalastat at the time of enrollment, having switched to commercial product

IV. Untreated patients

1. Patients with Fabry disease 18 years or older with amenable GLA variants, who have never been on treatment for Fabry disease, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment, and who meet local treatment guidelines for Fabry disease
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in annualized rate of decline eGFRCKD-EPI of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (\> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

V. ERT-treated patients

1. Patients with Fabry disease 18 years or older who have commenced ERT within 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment and are still being treated with ERT at the time of enrollment, and who have amenable GLA variants
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in eGFRCKD-EPI annualized rate of decline of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (\> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

All patients 1. All treated and untreated patients with Fabry disease who are enrolled in the study must be able to understand and provide written informed consent or assent.

Exclusion Criteria

1\. Patients who currently are participating in a clinical trial of any investigational medicinal product or device at the time of enrollment

Where this trial is running

Birmingham, Alabama and 7 other locations

• UAB Nephrology Research Clinic at Paula Building — Birmingham, Alabama, United States (Not_yet_recruiting)
• Arkansas Children's Hospital — Little Rock, Arkansas, United States (Recruiting)
• Emory Genetics — Atlanta, Georgia, United States (Recruiting)
• Washington University School of Medicine — St Louis, Missouri, United States (Not_yet_recruiting)
• New York-Presbyterian Morgan Stanley Children's Hospital - Columbia University Medical Center — New York, New York, United States (Not_yet_recruiting)
• UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (Not_yet_recruiting)
• Renal Disease Research Institute — Dallas, Texas, United States (Recruiting)
• Lysosomal and Rare Disorders Research and Treatment Center, Inc. — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Amicus Therapeutics Patient Advocacy

Conditions Fabry Disease; migalastat; AT1001; registry; lysosomal disease