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)

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.

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.

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.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

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.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.

To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease.

Number of subjects with abnormal electrocardiogram (ECG) findings as a measure of safety and tolerability

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

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

To evaluate the pharmacodynamics (PD) of migalastat in subjects with Fabry disease and severe renal impairment

Inclusion Criteria: 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 Exclusion Criteria: 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