- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04020055
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
Study Overview
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
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Amicus Therapeutics Patient Advocacy
- Phone Number: 609-662-2000
- Email: clinicaltrials@amicusrx.com
Study Locations
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Victoria
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Parkville, Victoria, Australia, 3050
- Recruiting
- Royal Melbourne Hospital
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Paris, France, 75020
- Recruiting
- Internal Medicine Unit Croix Saint Simon Hospital
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Osaka
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Suita, Osaka, Japan, 565-0871
- Recruiting
- Osaka University Hospital
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Coimbra, Portugal, 3041-801
- Not yet recruiting
- Centro Hospitalar e Universitário de Coimbra (CHUC)
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Barcelona, Spain, 08907
- Recruiting
- Hospital Universitari(o) de Bellvitge (HUB) Feixa Llarga
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Córdoba, Spain, 41013
- Recruiting
- Hospital Universitario Reina Sofia
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Elda, Spain, 03600
- Recruiting
- Hospital General Universitario de Elda
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Madrid, Spain, 28007
- Recruiting
- Hospital General Universitario Gregorio Maranon
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Georgia
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Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University
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Ohio
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Cleveland, Ohio, United States, 44195
- Not yet recruiting
- The Cleveland Clinic
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Texas
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Dallas, Texas, United States, 75235
- Recruiting
- Renal Disease Research Institute
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Virginia
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Fairfax, Virginia, United States, 22030
- Recruiting
- Lysosomal and Rare Disorders Research and Treatment Center, Inc
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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migalastat HCl 150 mg capsule
Other Names:
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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.
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migalastat HCl 150 mg capsule
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum observed concentration (Cmax)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Time to maximum concentration (tmax)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Apparent terminal elimination half-life (t½)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK
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Baseline through Month 12
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Concentration at the end of a dosing interval at steady state (Ctrough)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Average plasma migalastat concentration over the dosing interval (Cavg)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Area under the concentration-time curve at steady state during the dosing interval (AUC0-τ)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Apparent plasma clearance (CL/F)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK
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Baseline through Month 12
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Apparent terminal phase volume of distribution (Vz/F)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Dialysis clearance (CLD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Volume of dialysate collected during the interval (VD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Mean migalastat concentration in dialysate (CD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Amount recovered in dialysate (AeD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Fraction of the dose recovered in dialysate (FeD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Mean migalastat plasma concentration during the dialysis interval (P)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Mean inlet area under the curve (AUCinlet)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Mean outlet area under the curve (AUCoutlet)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Extraction ratio (ED)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Dialyzer blood flow (QD)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Cumulative amount excreted over all collection intervals (Ae0-τ)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Fraction of the dose recovered after the last measurable time point postdose (Fe0-τ)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Renal clearance (CLr)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-∞)
Time Frame: Baseline through Month 12
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To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
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Baseline through Month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events (AEs)
Time Frame: Baseline through Month 12
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To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease.
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Baseline through Month 12
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Number of subjects with abnormal clinical chemistry laboratory test results
Time Frame: Baseline through Month 12
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Blood samples will be collected for analysis of chemistry parameters.
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Baseline through Month 12
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Number of subjects with abnormal hematology laboratory test results
Time Frame: Baseline through Month 12
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Blood samples will be collected for analysis of hematology parameters.
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Baseline through Month 12
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Number of subjects with abnormal urinalysis laboratory test results
Time Frame: Baseline through Month 12
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Blood samples will be collected for analysis of urine parameters.
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Baseline through Month 12
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Number of subjects with abnormal electrocardiogram (ECG) findings as a measure of safety and tolerability
Time Frame: Baseline through Month 12
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A 12-lead ECG will be obtained
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Baseline through Month 12
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Change from baseline in estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFR MDRD)
Time Frame: Baseline through Month 12
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To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease
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Baseline through Month 12
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Change from baseline eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI)
Time Frame: Baseline through Month 12
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To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease
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Baseline through Month 12
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Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3)
Time Frame: Baseline through Month 12
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To evaluate the pharmacodynamics (PD) of migalastat in subjects with Fabry disease and severe renal impairment
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Baseline through Month 12
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Clinical Research, Amicus Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Urologic Diseases
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Cerebral Small Vessel Diseases
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Fabry Disease
Other Study ID Numbers
- AT1001-025
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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