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

Phase 3

Not yet recruiting

• Conditions: Fabry Disease
• Interventions: Drug: Migalastat HCl 20 mg

• Registration Number: NCT06904261
• Lead Sponsor: Amicus Therapeutics

Brief Summary

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.

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 Visit 1 (screening).

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 Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-13
• Study First Submitted QC: 2025-03-24
• Study First Posted: 2025-04-01
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-13
• Study Start: 2025-05
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Migalastat HCl 20 mg Dispersible Tablets	Migalastat HCl 20 mg	Migalastat will be administered every other day (QOD). The initial dose will be based on body weight at baseline.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Pharmacodynamic: Change in plasma levels of lyso-Gb3 and its analogs from baseline	Baseline to Months 3, 6, and 12/ET
Efficacy: Change in eGFR from baseline	Baseline to Months 1, 3, 6, and 12/ET	eGFR is calculated using the modified Schwartz formula for creatinine clearance.
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	Baseline to Month 12/ET	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.
Efficacy: Change in EQ-5D-Y scores from baseline (subjects aged ≥4 years)	Baseline to Month 12/ET	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.
Efficacy: Mean Patient's Global Impression Of Change (PGI-C) values	Months 3, 6, and 12/ET	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".
Efficacy: Change in PedsQL scores from baseline	Baseline to Month 12/ET	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.
Efficacy: Change in FPHPQ scores from baseline (subjects aged ≥4 years)	Baseline to Month 12/ET	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.

Trial Locations

Locations (1)

Lysosomal and Rare Disorders Research and Treatment Center, Inc.; 🇺🇸 Fairfax, Virginia, United States