A Study of Migalastat in Pediatric Subjects (2 to <12 Yrs) With Fabry Disease and Amenable GLA Variants

An Open-label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of 12 Month Treatment With Migalastat in Pediatric Subjects (Aged 2 to < 12 Years) With Fabry Disease and Amenable GLA Variants

An open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric subjects 2 to < 12 years of age with Fabry disease and with amenable GLA variants.

Study Overview

• Status: Recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Migalastat HCl 20 mg

Detailed Description

This is a Phase 3b, 2-stage, open-label, uncontrolled, multicenter study to evaluate the safety, PK, PD, and efficacy of 12 months of migalastat treatment in pediatric subjects 2 to < 12 years of age with Fabry disease and with amenable GLA variants. Subjects must be either naïve to enzyme replacement therapy (ERT) or have stopped ERT at least 14 days before Baseline visit.

The study will consist of 2 treatment stages followed by an open-label extension (OLE). Stage 1 will be a treatment period of approximately 3 months (12 weeks); Stage 2 will be a treatment period of 9 months. There will be no break in treatment between Stages 1 and 2. There will be a 30-day (untreated) safety follow-up period for subjects who discontinue treatment at any time.

Subjects will be randomly assigned 1:1:1 to 1 of 3 PK sampling groups using interactive response technology (IRT). Four blood samples for the determination of migalastat concentrations in plasma will be collected in one 24-hour period between Day 15 and Day 30 and at Month 6, and 1 PK (trough) sample will be collected at Month 6 and again at Month 12.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Amicus Therapeutics Patient Advocacy; Phone Number: 609-662-2000; Email: patientadvocacy@amicusrx.com

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Not yet recruiting
      • Universitair Ziekenhuis (Uz) Leuven
• Germany
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Recruiting
      • Universitäetsklinikum Müenster (UKM) Klinik für Kinder- und Jugendmedizin - Allgemeine Paediatrie
• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28046
      • Recruiting
      • Hospital Universitario de La Paz
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Not yet recruiting
    • Great Ormond Street Hospital For Children NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Manchester University NHS Foundation Trust
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory Genetics
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Masonic Children's Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health Levine Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Not yet recruiting
      • UPMC Children's Hospital of Pittsburgh
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Recruiting
      • Lysosomal and Rare Disorders Research and Treatment Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Male or female subjects, diagnosed with Fabry disease who are between ages 2 and < 12 years at randomization (subjects aged 11 years must have birthdays > 30 days after randomization)
• 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 has a GLA variant documented in his/her medical record that is amenable to migalastat prior to Visit 2.
• Subject has not received ERT (eg, Replagal® [agalsidase alfa] or Fabrazyme® [agalsidase beta]) for at least 14 days prior to Baseline visit.
• Subject has at least 1 documented complication (ie, historical or current laboratory abnormality or sign/symptom) of Fabry disease
• If of reproductive potential, both male and female subjects agree to use a medically accepted method of contraception throughout the duration of the study and for up to 30 days after their last dose of migalastat.

Exclusion Criteria

• Has moderate or severe renal impairment (eGFR < 60 mL/min/1.73 m2 at Visit 1 [screening]).
• Has advanced kidney disease requiring dialysis or kidney transplantation.
• History of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
• Has received any investigational/experimental drug, biologic, or device within 30 days or 5 half-lives of the investigational product (whichever is longer) before Visit 1 (screening).
• Has received any gene therapy at any time or anticipates starting gene therapy during the study period.
• Requires treatment with Glyset (miglitol) or Zavesca (miglustat), within 6 months before Visit 1(screening) or throughout the study.
• Has any intercurrent illness or condition at Visit 1 (screening) or Visit 2 (baseline) 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 breastfeeding
• 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 20 mg Dispersible Tablets; Migalastat will be administered every other day (QOD). The initial dose will be based on body weight at baseline.	Drug: Migalastat HCl 20 mg; Migalastat will be supplied as 20-mg dispersible tablets. Migalastat 20-mg dispersible tablets contain 16 mg migalastat free base.; Other Names: AT1001; Galafold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug	Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Migalastat	0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
Pharmacokinetics (PK): Minimum Observed Plasma Concentration (Cmin) of Migalastat	0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve Over The Dosing Interval (AUCtau) of Migalastat	0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic: Change in plasma levels of lyso-Gb3 and its analogs from baseline		Baseline to Months 3, 6, and 12/ET
Efficacy: Change in urine protein and albumin/microalbumin levels from baseline		Baseline to Months 3, 6, and 12/ET
Efficacy: Change in Left Ventricular Mass Index (LVMi) from baseline		Baseline to Month 12/ET
Efficacy: Change in FABPRO-GI And Pain Scores from baseline	The Fabry Disease Patient-Reported Outcome - Gastrointestinal Signs And Symptoms (FABPRO-GI) And Pain Questionnaire For Clinical Trials (24-hr Version) consists of questions regarding gastrointestinal signs and symptoms and pain relative to the past 24 hours. Participants rate the severity of their symptoms and pain from 0 (none) to 10 (worst possible). A higher score indicated higher levels of symptoms and pain.	Baseline to Month 12/ET
Efficacy: Mean Patient's Global Impression Of Change (PGI-C) values	The PGI-C consists of 4 questions regarding diarrhea, abdominal pain, overall pain, and daily living. Participants rate their status based on improvement, worsening, or the same. Improved status includes "Much better", "Better" and "A little better"; worsened status includes "A little worse", "Worse" and "Much worse".	Months 3, 6, and 12/ET
Efficacy: Change in EQ-5D-Y scores from baseline (subjects aged ≥4 years)	The EuroQol 5-dimension Youth Questionnaire [EQ-5D-Y] is a two-part instrument: the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system covers five health domains: mobility, looking after myself, doing usual activities, having pain or discomfort and feeling worried, sad or unhappy. Each domain has 3 response categories: no problems, some problems and a lot of problems. The response categories can be reflected by a 1-digit number (1-3) and combined for the five dimensions into a 5-digit number to describe the health state of the patient. The EQ VAS records the patient's self-rated health on a vertical VAS of 0-100 where 100="The best health you can imagine" and 0="The worst health you can imagine". The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	Baseline to Month 12/ET
Efficacy: Change in PedsQL scores from baseline	The Pediatric Quality of Life Inventory™ (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. The psychosocial score for the PedsQL encompasses 15 questions relating to the participants' feelings, social interaction with others, and school. The physical score is derived from answers to 8 questions about the participants' ease of managing physical activity. All components of the PedsQL are scored based on a scale of 0 (never) to 4 (almost always) and linearly transformed to a 0-100 scale as follows: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0. Both categories are combined for a total score.	Baseline to Month 12/ET
Efficacy: Change in FPHPQ scores from baseline (subjects aged ≥4 years)	The Fabry-specific Pediatric Health and Pain Questionnaire (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, often, sometimes, seldom, never). Pain intensity is measured on a 10-point scale with numeric responses given for onset of pain and school days missed, and yes/no questions posed about difficulty hearing and other problems not specifically mentioned.	Baseline to Month 12/ET
Efficacy: Change in eGFR from baseline	eGFR is calculated using the modified Schwartz formula for creatinine clearance. eGFR will also be calculated separately using the CKD-EPI40 equation.	Baseline to Months 1, 3, 6, and 12/ET

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 13, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: AT1001; Galafold; migalastat; lysosomal disease
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Fabry Disease; migalastat; larazotide acetate
• Other Study ID Numbers: AT1001-033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing proposals and requests will be reviewed on a case-by-case basis. Requests for data should be addressed to Nick Rees at nrees@amicusrx.com. Requests will be reviewed by a medical steering committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No