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Safety, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged >12 Years) with Fabry Disease

Phase 3
Completed
Conditions
Fabry Disease
Interventions
Registration Number
NCT04049760
Lead Sponsor
Amicus Therapeutics
Brief Summary

This is a long-term, Open-label Study to Evaluate the Safety, Pharmacodynamics, and Efficacy of Migalastat in Subjects \> 12 Years of Age With Fabry Disease and Amenable GLA Variants

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
Inclusion Criteria
  • Male or female subjects diagnosed with Fabry disease > 12 years of age who completed Study AT1001-020
  • Subject's parent or legally-authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable
  • Subject's parent or legally-authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable
Exclusion Criteria
  • Has moderate or severe renal impairment (eGFR <60 ml/min/1.73 m2 at screening)
  • Has advanced kidney disease requiring dialysis or kidney transplantation
  • History of allergy or sensitivity to study medication (including excipients) or other iminosugars (eg, miglustat, miglitol)
  • Has received any gene therapy at any time or anticipates starting gene therapy during the study period
  • Requires treatment with Glyset (miglitol), Zavesca (miglustat) within 6 months before screening or throughout the study
  • Requires treatment with Replagal (agalsidase alfa), or Fabrazyme (agalsidase beta) within 14 days before screening or throughout the study
  • Subject is treated or has been treated with any investigational/experimental drug, biologic or device within 30 days before screening
  • Any intercurrent illness or condition or concomitant medication use considered to be a contraindication at screening or baseline or that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study
  • Pregnant or breast-feeding
  • Otherwise unsuitable for the study in the opinion of the investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
migalastat HCl 150 mgmigalastat HCl 150 mgOne migalastat 123 mg capsule equivalent to 150 mg migalastat HCl will be administered every other day (QOD) during the treatment period.
Primary Outcome Measures
NameTimeMethod
change in body weight in kilogramsbaseline over time; Up to 5 years
incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to discontinuation of study drugMonth 60
changes in Electrocardiogram (ECG) resultsbaseline over time; Up to 5 years

A 12-lead ECG will be obtained.

incidence of changes in echocardiogram resultsbaseline over time; Up to 5 years

Systolic and diastolic heart function and structure is assessed by ultrasound of the heart. Echocardiogram parameters include left ventricular mass index (LVMi), ejection fraction, fractional shortening, left ventricular internal diameter end diastole and end systole, midwall fractional shortening, and wall thickness.

change in height in centimetersbaseline over time; Up to 5 years
change in Tanner stageEvery 6 Months; Up to 5 years

Tanner Staging of Sexual Development will be used to assess sexual development (i.e. breast development (B1 to B5) and pubic hair development (Ph-1 to Ph-5) in females and pubic hair and genetical development (G1-G5) in males.

incidence of concomitant medications useEvery 1 Month; Up to 5 years
Secondary Outcome Measures
NameTimeMethod
change in plasma levels of lyso-Gb3Every 6 Months; Up to 5 years
change in eGFREvery 6 Months; Up to 5 years
change in urine proteinEvery 6 Months; Up to 5 years
change in albumin levelsEvery 6 Months; Up to 5 years
change in Fabry-Specific Pediatric Health and Pain Questionnaire (FPHPQ)scoresEvery 3 months; Up to 5 years

The FPHPQ includes questions about Fabry disease-specific symptoms (eg, sweating, pain, dizziness and tiredness, heat and cold intolerance, swollen eyelids, gastrointestinal symptoms, feeling thirsty, difficulty hearing, ringing or buzzing noise in the ears, and ability and enjoyment to participate in sports). The frequency of these symptoms will be rated using a 5-point Likert scale (always (worse), often, sometimes, seldom, never (better)). Pain intensity is measured on a 10-point scale, numeric responses are given for onset of pain and school days missed, and yes/no questions are posed about difficulty hearing and other problems not specifically mentioned. There are 2 age-specific self-report versions for children 8 to 12 years and 13 to 18 years, respectively.

change in Left Ventricular Mass Index (LVMi)Every Year; Up to 5 years
change in Pediatric and Quality of Life Inventory™ (PedsQL™) scoresEvery 3 months; Up to 5 years

The PedsQL™ is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. It consists of 23 items and includes questions about physical functioning, emotional functioning, social functioning, and school functioning relative to the prior 7 days, using a 5-point scale (never (better), almost never, sometimes, often and almost always (worse)). Both parents or legally-authorized representatives and subjects complete the appropriate version of the PedsQL independently of one another. Parents or legally-authorized representatives and subjects may self-administer the questions after introductory instructions are given by study site personnel.

Trial Locations

Locations (6)

The Emory Clinic

🇺🇸

Atlanta, Georgia, United States

University of Minnesota Masonic Children's Hospital and Clinics

🇺🇸

Minneapolis, Minnesota, United States

Lysosomal & Rare Disorders Research & Treatment Center

🇺🇸

Fairfax, Virginia, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Royal Free London NHS Foundation Trust

🇬🇧

London, United Kingdom

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