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

Phase 3Active Not RecruitingNCT04020055

Amicus Therapeutics14 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Fabry Disease

Interventions

migalastat HCl 150 mgDRUG

migalastat HCl 150 mg capsule

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

Emory University

Atlanta, Georgia, United States

The Cleveland Clinic

Cleveland, Ohio, United States

Lysosomal and Rare Disorders Research and Treatment Center, Inc

Fairfax, Virginia, United States

Outcomes

Primary Outcomes

Maximum observed concentration (Cmax)

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

Time frame: 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.

Time frame: Baseline through Month 12

Apparent terminal elimination half-life (t½)

To characterize the pharmacokinetics (PK) of migalastat and validate the population PK

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

Adverse events (AEs)

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline through Month 12