Fabry Disease
Conditions
Keywords
Renal Disease, Severe Renal Impairment (SRI), End-Stage Renal Disease (ESRD)
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)
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.
Interventions
migalastat HCl 150 mg capsule
Sponsors
Amicus Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Time to maximum concentration (tmax) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Apparent terminal elimination half-life (t½) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK |
| Concentration at the end of a dosing interval at steady state (Ctrough) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Average plasma migalastat concentration over the dosing interval (Cavg) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Area under the concentration-time curve at steady state during the dosing interval (AUC0-τ) | Baseline through Month 12 | 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-∞) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Apparent plasma clearance (CL/F) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK |
| Apparent terminal phase volume of distribution (Vz/F) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Dialysis clearance (CLD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Volume of dialysate collected during the interval (VD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Mean migalastat concentration in dialysate (CD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Amount recovered in dialysate (AeD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Fraction of the dose recovered in dialysate (FeD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Mean migalastat plasma concentration during the dialysis interval (P) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Mean inlet area under the curve (AUCinlet) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Mean outlet area under the curve (AUCoutlet) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Extraction ratio (ED) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Dialyzer blood flow (QD) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Cumulative amount excreted over all collection intervals (Ae0-τ) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Fraction of the dose recovered after the last measurable time point postdose (Fe0-τ) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
| Renal clearance (CLr) | Baseline through Month 12 | To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) | Baseline through Month 12 | To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease. |
| 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 | 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) | Baseline through Month 12 | To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease |
| Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3) | Baseline through Month 12 | To evaluate the pharmacodynamics (PD) of migalastat in subjects with Fabry disease and severe renal impairment |
Countries
Australia, Japan, Portugal, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Research
Amicus Therapeutics
Outcome results
None listed