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

PHASE3ACTIVE_NOT_RECRUITING

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

  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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT04020055

Intervention or treatment

DRUG: migalastat HCl 150 mg

Conditions

  • Fabry Disease

  • Condition: Fabry Disease

  • DRUG: migalastat HCl 150 mg

  • Parkville, Victoria, Australia and more

  • Sponsor: Amicus Therapeutics

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Royal Melbourne Hospital

Select from list below to view details:

  • Royal Melbourne Hospital

    Parkville, Victoria, Australia

  • Royal Perth Hospital

    Perth, Washington, Australia

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Who is running the clinical trial?

AT

Amicus Therapeutics

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/ArmIntervention/Treatment
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.
    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.
    Drug: migalastat HCl 150 mg

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime 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 PKBaseline 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 PKBaseline 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

      MeasureDescriptionTime 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
      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 diseaseBaseline 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 diseaseBaseline 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 impairmentBaseline through Month 12
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: A Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease

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