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

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04020055
• Other study ID #: AT1001-025
• Status: Recruiting
• Phase: Phase 3
• Start date: October 31, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Amicus Therapeutics
• Contact: Amicus Therapeutics Patient Advocacy
• Phone: 609-662-2000
• Email: clinicaltrials[@]amicusrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fabry Disease
• Kidney Diseases

Intervention

Drug:
• migalastat HCl 150 mg
migalastat HCl 150 mg capsule

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Parkville	Victoria
France	Internal Medicine Unit Croix Saint Simon Hospital	Paris
Japan	Osaka University Hospital	Suita	Osaka
Portugal	Centro Hospitalar e Universitário de Coimbra (CHUC)	Coimbra
Spain	Hospital Universitari(o) de Bellvitge (HUB) Feixa Llarga	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital General Universitario de Elda	Elda
Spain	Hospital General Universitario Gregorio Marañon	Madrid
United States	Emory University	Atlanta	Georgia
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Renal Disease Research Institute	Dallas	Texas
United States	Lysosomal and Rare Disorders Research and Treatment Center, Inc	Fairfax	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Amicus Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  France,  Japan,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed concentration (Cmax)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	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
Primary	Apparent terminal elimination half-life (t½)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK	Baseline through Month 12
Primary	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
Primary	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
Primary	Area under the concentration-time curve at steady state during the dosing interval (AUC0-t)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-8)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Apparent plasma clearance (CL/F)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK	Baseline through Month 12
Primary	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
Primary	Dialysis clearance (CLD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Extraction ratio (ED)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Dialyzer blood flow (QD)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Cumulative amount excreted over all collection intervals (Ae0-t)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Fraction of the dose recovered after the last measurable time point postdose (Fe0-t)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Primary	Renal clearance (CLr)	To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.	Baseline through Month 12
Secondary	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
Secondary	Number of subjects with abnormal clinical chemistry laboratory test results	Blood samples will be collected for analysis of chemistry parameters.	Baseline through Month 12
Secondary	Number of subjects with abnormal hematology laboratory test results	Blood samples will be collected for analysis of hematology parameters.	Baseline through Month 12
Secondary	Number of subjects with abnormal urinalysis laboratory test results	Blood samples will be collected for analysis of urine parameters.	Baseline through Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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