Clinical trial NCT04020055: A Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Renal Disease
Severe Renal Impairment (SRI)
End-Stage Renal Disease (ESRD)
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-07-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Baseline through Month 12
measure: Time to maximum concentration (tmax)
timeFrame: Baseline through Month 12
measure: Apparent terminal elimination half-life (t½)
timeFrame: Baseline through Month 12
measure: Concentration at the end of a dosing interval at steady state (Ctrough)
timeFrame: Baseline through Month 12
measure: Average plasma migalastat concentration over the dosing interval (Cavg)
timeFrame: Baseline through Month 12
measure: Area under the concentration-time curve at steady state during the dosing interval (AUC0-τ)
timeFrame: Baseline through Month 12
measure: Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-∞)
timeFrame: Baseline through Month 12
measure: Apparent plasma clearance (CL/F)
timeFrame: Baseline through Month 12
measure: Apparent terminal phase volume of distribution (Vz/F)
timeFrame: Baseline through Month 12
measure: Dialysis clearance (CLD)
timeFrame: Baseline through Month 12
measure: Volume of dialysate collected during the interval (VD)
timeFrame: Baseline through Month 12
measure: Mean migalastat concentration in dialysate (CD)
timeFrame: Baseline through Month 12
measure: Amount recovered in dialysate (AeD)
timeFrame: Baseline through Month 12
measure: Fraction of the dose recovered in dialysate (FeD)
timeFrame: Baseline through Month 12
measure: Mean migalastat plasma concentration during the dialysis interval (P)
timeFrame: Baseline through Month 12
measure: Mean inlet area under the curve (AUCinlet)
timeFrame: Baseline through Month 12
measure: Mean outlet area under the curve (AUCoutlet)
timeFrame: Baseline through Month 12
measure: Extraction ratio (ED)
timeFrame: Baseline through Month 12
measure: Dialyzer blood flow (QD)
timeFrame: Baseline through Month 12
measure: Cumulative amount excreted over all collection intervals (Ae0-τ)
timeFrame: Baseline through Month 12
measure: Fraction of the dose recovered after the last measurable time point postdose (Fe0-τ)
timeFrame: Baseline through Month 12
measure: Renal clearance (CLr)
timeFrame: Baseline through Month 12
Secondary outcomes:
measure: Adverse events (AEs)
timeFrame: Baseline through Month 12
measure: Change from baseline in estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFR MDRD)
timeFrame: Baseline through Month 12
measure: Change from baseline eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI)
timeFrame: Baseline through Month 12
measure: Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3)
timeFrame: Baseline through Month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: Renal Disease Research Institute
state: Texas
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center, Inc
state: Virginia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Washington
city: Paris
country: France
facility: Internal Medicine Unit Croix Saint Simon Hospital
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra (CHUC)
city: Barcelona
country: Spain
facility: Hospital Universitari(o) de Bellvitge (HUB) Feixa Llarga
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Elda
country: Spain
facility: Hospital General Universitario de Elda
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
affiliation: Amicus Therapeutics
name: Clinical Research
role: STUDY_DIRECTOR
References: