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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 (SRI) or End Stage Renal Disease (ESRD).
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2022-10-31
Primary completion: 2024-12-31
Study completion finish: 2025-12-31
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT04020055
Intervention or treatment
DRUG: migalastat HCl 150 mg
Conditions
- • Fabry Disease
Find a site
Closest Location:
Royal Melbourne Hospital
Research sites nearby
Select from list below to view details:
Royal Melbourne Hospital
Parkville, Victoria, Australia
Royal Perth Hospital
Perth, Washington, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Cohort 1: Severe Renal Impairment
| DRUG: migalastat HCl 150 mg
|
EXPERIMENTAL: Cohort 2: End-Stage Renal Disease
| DRUG: migalastat HCl 150 mg
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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 outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Adverse events (AEs) | To assess the safety and tolerability of migalastat in Fabry subjects with severe renal impairment and end stage renal disease. | Baseline through Month 12 |
Number of subjects with abnormal clinical chemistry laboratory test results | Blood samples will be collected for analysis of chemistry parameters. | Baseline through Month 12 |
Number of subjects with abnormal hematology laboratory test results | Blood samples will be collected for analysis of hematology parameters. | Baseline through Month 12 |
Number of subjects with abnormal urinalysis laboratory test results | Blood samples will be collected for analysis of urine parameters. | Baseline through Month 12 |
Number of subjects with abnormal electrocardiogram (ECG) findings as a measure of safety and tolerability | A 12-lead ECG will be obtained | 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 | 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 | 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 | Baseline through Month 12 |
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