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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: migalastat HCl 150 mg

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Royal Free London NHS Foundation Trust
• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Masonic Children's Hospital and Clinics
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal & Rare Disorders Research & Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: migalastat HCl 150 mg; One migalastat 123 mg capsule equivalent to 150 mg migalastat HCl will be administered every other day (QOD) during the treatment period.	Drug: migalastat HCl 150 mg; migalastat HCl 150 mg capsule; Other Names: AT1001; migalastat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to discontinuation of study drug		Month 60
change in body weight in kilograms		baseline over time; Up to 5 years
change in height in centimeters		baseline over time; Up to 5 years
changes in Electrocardiogram (ECG) results	A 12-lead ECG will be obtained.	baseline over time; Up to 5 years
incidence of changes in echocardiogram results	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.	baseline over time; Up to 5 years
change in Tanner stage	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.	Every 6 Months; Up to 5 years
incidence of concomitant medications use		Every 1 Month; Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in plasma levels of lyso-Gb3		Every 6 Months; Up to 5 years
change in eGFR		Every 6 Months; Up to 5 years
change in urine protein		Every 6 Months; Up to 5 years
change in albumin levels		Every 6 Months; Up to 5 years
change in Left Ventricular Mass Index (LVMi)		Every Year; Up to 5 years
change in Fabry-Specific Pediatric Health and Pain Questionnaire (FPHPQ)scores	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.	Every 3 months; Up to 5 years
change in Pediatric and Quality of Life Inventory™ (PedsQL™) scores	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.	Every 3 months; Up to 5 years

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: migalastat; Lysosomal storage disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AT1001-036; 2019-000222-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No