A Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease

An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects With Fabry Disease and Amenable GLA Variants and Severe Renal Impairment or End-Stage Renal Disease Treated With Hemodialysis

An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects with Fabry Disease and Amenable GLA Variants and Severe Renal Impairment (SRI) or End Stage Renal Disease (ESRD)

Study Overview

• Status: Active, not recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: migalastat HCl 150 mg

Detailed Description

This is an open-label, non-comparative study for subjects with Fabry disease who have an estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFRMDRD) value of < 30 mL/min/1.73 m2. Subjects may have had previous exposure to migalastat, either commercially or as a participant in a previous migalastat study.

Two distinct populations of subjects with Fabry disease and renal impairment will be enrolled into this study:

• Cohort 1: Subjects with SRI not receiving any type of dialysis treatment
• Cohort 2: ESRD subjects who are receiving hemodialysis treatment, either standard hemodialysis (HD) or hemodiafiltration (HDF). Only subjects who can receive HD/HDF at the study clinic or at an affiliated center where the Investigator already has oversight should be enrolled into Cohort 2.

Subjects entering into this study will undergo screening (Visit 1) to confirm enrollment eligibility including confirmatory GLA genotyping. Subjects who meet eligibility criteria will have a Baseline Visit (Visit 2) within 30 days of screening. Subjects who do not meet eligibility criteria (eg, subjects with an eGFR > 30 mL/min/1.73 m2) may be re-screened.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Washington
    • Perth, Washington, Australia, 6000
      • Royal Perth Hospital
• Japan
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Shizuoka
    • Shizuoka, Shizuoka, Japan, 420-8527
      • Shizuoka General Hospital
• Portugal
  • Coimbra, Portugal, 3041-801
    • Centro Hospitalar e Universitário de Coimbra (CHUC)
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari(o) de Bellvitge (HUB) Feixa Llarga
  • Elda, Spain, 03600
    • Hospital General Universitario de Elda
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
• United Kingdom
  • England
    • Salford, England, United Kingdom, M6 8HD
      • Salford Royal Hospital
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Disorders Research and Treatment Center, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects aged 18 years or older, diagnosed with Fabry disease.
2. Subject (or legally authorized representative as applicable) is willing and able to provide written informed consent and authorization for use and disclosure of Personal Health Information
3. Subject has a GLA variant that is amenable to migalastat recorded in their medical records
4. Subject has at least 1 documented eGFR value of < 30 mL/min/1.73 m2 within the last 3 months and has an eGFRMDRD value of < 30 mL/min/1.73 m2 at Visit 1
5. Subjects with ESRD have been on a stable 2- or 3-times a week HD (standard or HDF) regimen for at least 2 months prior to the screening visit
6. Subjects with ESRD must commit to completing at least 4 standard HD or HDF sessions during each 2-week dosing interval.
7. Subjects with ESRD must commit to completing the entire prescribed duration for each dialysis session.
8. If of reproductive potential, both male and female patients agree to use a medically accepted method of contraception

Exclusion Criteria:

1. Subject has undergone kidney transplantation
2. Subject is on peritoneal dialysis
3. Subject is treated or has been treated with another investigational drug (except migalastat) within the 30 days
4. Subject has undergone any gene therapy at any time prior to the study or anticipates undergoing gene therapy during the study.
5. Subject has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction
6. Subject has clinically significant unstable cardiac disease
7. Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements
8. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol)
9. Subject requires concurrent treatment with Glyset® (miglitol), Replagal® (agalsidase alfa), or Fabrazyme® (agalsidase beta)
10. Subject requires concurrent treatment with Zavesca® (miglustat) or has been treated with Zavesca
11. Female subject is pregnant or breast-feeding
12. Subject is unable to comply with study requirements
13. In France only, protected persons as defined by the Public Health Code

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Severe Renal Impairment; All subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat) at a dose regimen based on their eGFRMDRD result at Visit 1. Subjects will take 1 migalastat capsule orally with water either every 4 or 7 days.	Drug: migalastat HCl 150 mg; migalastat HCl 150 mg capsule; Other Names: AT1001; migalastat
Experimental: Cohort 2: End-Stage Renal Disease; All hemodialysis subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat). Subjects will take 1 migalastat capsule orally with water every other week.	Drug: migalastat HCl 150 mg; migalastat HCl 150 mg capsule; Other Names: AT1001; migalastat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Time to maximum concentration (tmax)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Apparent terminal elimination half-life (t½)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK	Baseline through Month 12
Concentration at the end of a dosing interval at steady state (Ctrough)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Average plasma migalastat concentration over the dosing interval (Cavg)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Area under the concentration-time curve at steady state during the dosing interval (AUC0-τ)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Apparent plasma clearance (CL/F)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK	Baseline through Month 12
Apparent terminal phase volume of distribution (Vz/F)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Dialysis clearance (CLD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Volume of dialysate collected during the interval (VD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Mean migalastat concentration in dialysate (CD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Amount recovered in dialysate (AeD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Fraction of the dose recovered in dialysate (FeD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Mean migalastat plasma concentration during the dialysis interval (P)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Mean inlet area under the curve (AUCinlet)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Mean outlet area under the curve (AUCoutlet)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Extraction ratio (ED)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Dialyzer blood flow (QD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Cumulative amount excreted over all collection intervals (Ae0-τ)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Fraction of the dose recovered after the last measurable time point postdose (Fe0-τ)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Renal clearance (CLr)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-∞)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease.	Baseline through Month 12
Change from baseline in estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFR MDRD)	To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease	Baseline through Month 12
Change from baseline eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI)	To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease	Baseline through Month 12
Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3)	To evaluate the pharmacodynamics (PD) of migalastat in subjects with Fabry disease and severe renal impairment	Baseline through Month 12

Collaborators and Investigators

• Sponsor: Amicus Therapeutics
• Investigators: Study Director: Clinical Research, Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Renal Disease; Severe Renal Impairment (SRI); End-Stage Renal Disease (ESRD)
• Additional Relevant MeSH Terms: Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; 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; Renal Insufficiency, Chronic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Kidney Failure, Chronic; Fabry Disease; migalastat; larazotide acetate
• Other Study ID Numbers: AT1001-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No