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

NCT04020055 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: AT1001-025
• Study Type: interventional
• Target: 14
• Locations: 6 countries
• Sites: 12

Brief Summary

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)

Conditions

Fabry Disease

Keywords

Renal Disease; Severe Renal Impairment (SRI); End-Stage Renal Disease (ESRD)

Outcome Measures

Primary Outcomes (22)

• 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

• 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

• 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

Secondary Outcomes (4)

• Adverse events (AEs)

  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)

  Baseline through Month 12

• Change from baseline eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI)

  Baseline through Month 12

• Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3)

  Baseline through Month 12

Study Arms (2)

Cohort 1: Severe Renal Impairment

EXPERIMENTAL

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.

Cohort 2: End-Stage Renal Disease

EXPERIMENTAL

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

Interventions

migalastat HCl 150 mg DRUG

migalastat HCl 150 mg capsule

Also known as: migalastat, AT1001

Cohort 2: End-Stage Renal Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 years or older, diagnosed with Fabry disease.
• 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
• Subject has a GLA variant that is amenable to migalastat recorded in their medical records
• 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
• 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
• Subjects with ESRD must commit to completing at least 4 standard HD or HDF sessions during each 2-week dosing interval.
• Subjects with ESRD must commit to completing the entire prescribed duration for each dialysis session.
• If of reproductive potential, both male and female patients agree to use a medically accepted method of contraception

You may not qualify if:

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

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (12)

Emory University

Atlanta, Georgia, 30322, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center, Inc

Fairfax, Virginia, 22030, United States

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Perth Hospital

Perth, Washington, 6000, Australia

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Shizuoka General Hospital

Shizuoka, Shizuoka, 420-8527, Japan

Location

Centro Hospitalar e Universitário de Coimbra (CHUC)

Coimbra, 3041-801, Portugal

Location

Hospital Universitari(o) de Bellvitge (HUB) Feixa Llarga

Barcelona, 08907, Spain

Location

Hospital General Universitario de Elda

Elda, 03600, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Salford Royal Hospital

Salford, England, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Fabry Disease; Kidney Diseases; Renal Insufficiency; Kidney Failure, Chronic

Interventions

migalastat; larazotide acetate

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; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: July 15, 2019
• Study Start: October 31, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 14, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2); AU (2); GB (1); ES (3); US (3); PT (1)