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

Safety: Incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug

Time frame · Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Migalastat

Time frame · 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

Time frame · 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

Time frame · 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

Pharmacodynamic: Change in plasma levels of lyso-Gb3 and its analogs from baseline

Time frame · Baseline to Months 3, 6, and 12/ET

Efficacy: Change in eGFR from baseline

Time frame · Baseline to Months 1, 3, 6, and 12/ET

eGFR is calculated using the modified Schwartz formula for creatinine clearance. eGFR will also be calculated separately using the CKD-EPI40 equation.

Efficacy: Change in urine protein and albumin/microalbumin levels from baseline

Time frame · Baseline to Months 3, 6, and 12/ET

Efficacy: Change in Left Ventricular Mass Index (LVMi) from baseline

Time frame · Baseline to Month 12/ET

Efficacy: Change in FABPRO-GI And Pain Scores from baseline

Time frame · 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: Mean Patient's Global Impression Of Change (PGI-C) values

Time frame · 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 EQ-5D-Y scores from baseline (subjects aged ≥4 years)

Time frame · 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: Change in PedsQL scores from baseline

Time frame · 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)

Time frame · 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.