NCT03500094

Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)

Completed Phase 3 Results posted Last updated 30 November 2021

What this trial tests

Phase 3 trial testing Migalastat HCl 150 mg in Fabry Disease in 22 participants. Completed in 6 February 2021.

Timeline

27 September 2018

Primary endpoint
2 February 2021

6 February 2021

Quick facts

Lead sponsor	Amicus Therapeutics
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	22
Start date	27 September 2018
Primary completion	2 February 2021
Estimated completion	6 February 2021
Sites	8 locations across United Kingdom, United States

Drugs / interventions tested

• Migalastat HCl 150 mg — full drug profile →

Conditions studied

• Fabry Disease — all drugs for Fabry Disease →

Sponsor

Amicus Therapeutics — full company profile →

Who can join

Adults 12 to 17, any sex, with Fabry Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number Of Participants Who Experienced Treatment-related Treatment-emergent Adverse Events (TEAEs) Primary · Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)

TEAEs included adverse events that began on or after the first dose of study drug until 30 days after the last dose. Treatment-related TEAEs were defined as TEAEs that had an investigator-defined relationship to study drug of "Definite," "Probable," or "Possible." A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Group	Value	95% CI
Migalastat HCl 150 mg	5

Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve Over The Dosing Interval (AUCtau) Of Migalastat Primary · 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25 hours (h), 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in r

12 to <16 years old

Group	Value	95% CI
Migalastat HCl 150 mg	8920	± 47.2

16 to <18 years old

Group	Value	95% CI
Migalastat HCl 150 mg	8430	± 41.7

12 to <18 years old

Group	Value	95% CI
Migalastat HCl 150 mg	8740	± 44.2

PK: Maximum Observed Plasma Concentration (Cmax) Of Migalastat Primary · 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25h, 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in rich data

12 to <16 years old

Group	Value	95% CI
Migalastat HCl 150 mg	1220	± 60.9

16 to <18 years old

Group	Value	95% CI
Migalastat HCl 150 mg	1160	± 39.2

12 to <18 years old

Group	Value	95% CI
Migalastat HCl 150 mg	1200	± 52.7

Change In eGFR From Baseline To Month 12 Secondary · Baseline, Month 12 and last observation (up to Month 12)

eGFR was calculated using the modified Schwartz formula for creatinine clearance.

Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	-1.6	± 15.40

Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	-1.6	± 14.99

Annualized Rate Of Change From Baseline Secondary · Baseline up to Month 12

Annualized rate of change from baseline of eGFR was defined as change from baseline to last visit divided by the duration from baseline to the last visit (Last assessment date - First dose date +1) and multiplied by 365.25. Baseline was defined as the last non-missing assessment prior to the first dose of study drug.

Group	Value	95% CI
Migalastat HCl 150 mg	-1.5	± 15.11

Change From Baseline In Total Urine Protein And Urine Albumin Levels At Month 12 Secondary · Baseline, Month 12 and last observation (up to Month 12)

Renal function was assessed by urine protein and urine albumin levels. Urine samples were collected as part of urinalysis to measure protein and albumin levels.

Total Urine Protein: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	36.0	± 111.61

Total Urine Protein: Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	36.2	± 108.64

Urine Albumin: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	16.2	± 28.27

Urine Albumin: Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	15.6	± 27.67

Change From Baseline In Left Ventricular Mass Index (LVMi) Secondary · Baseline, Month 12 and last observation (up to Month 12)

LVMi was assessed as a measure of cardiac impairment in the study participants. LVMi values for both M Mode and 2D views are presented.

M Mode: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	-3.9	± 13.53

2D: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	4.9	± 9.12

M Mode: Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	-4.4	± 13.31

2D: Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	4.3	± 9.34

Change In Plasma Levels Of Globotriaosylsphingosine (Lyso-Gb3) Secondary · Baseline, Month 12 and last observation (up to Month 12)

Blood samples were collected for measurement of lyso-Gb3 levels in plasma. Plasma levels of lyso-Gb3 were measured using a validated liquid chromatography-mass spectrometry assay.

Month 12

Group	Value	95% CI
Migalastat HCl 150 mg: ERT Naive	-14.0	± 23.13
Migalastat HCl 150 mg: ERT Experienced	12.5	± 36.33

Last Observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg: ERT Naive	-14.0	± 23.13
Migalastat HCl 150 mg: ERT Experienced	11.3	± 34.67

FABPRO-GI And Pain Scores Secondary · Month 12 and last observation (up to Month 12)

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 rated the severity of their symptoms and pain from 0 (none) to 10 (worst possible). The monthly average score at Month 12 and at last observation are presented. A higher score indicated higher levels of symptoms and pain.

Daily Ratings of Severity in Constipation: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	0.9	± 1.91

Daily Ratings of Severity in Constipation: Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	0.4	± 1.00

Daily Ratings of Severity in Diarrhea: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	1.0	± 1.65

Daily Ratings of Severity in Diarrhea: Last Observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	0.4	± 0.91

Overall Pain: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	0.6	± 0.71

Overall Pain: Last Observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	1.2	± 1.50

Worst Tummy Pain: Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	0.3	± 0.38

Worst Tummy Pain: Last Observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	0.9	± 1.52

Patient's Global Impression Of Change (PGI-C) Scores Secondary · Month 12

The PGI-C consists of 4 questions regarding diarrhea, abdominal pain, overall pain, and daily living. Participants rated 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".

Diarrhea: Status Improved

Group	Value	95% CI
Migalastat HCl 150 mg	12

Diarrhea: Status Same

Group	Value	95% CI
Migalastat HCl 150 mg	7

Diarrhea: Status Worse

Group	Value	95% CI
Migalastat HCl 150 mg	0

Abdominal pain: Status Improved

Group	Value	95% CI
Migalastat HCl 150 mg	10

Abdominal pain: Status Same

Group	Value	95% CI
Migalastat HCl 150 mg	8

Abdominal pain: Status Worse

Group	Value	95% CI
Migalastat HCl 150 mg	1

Overall pain: Status Improved

Group	Value	95% CI
Migalastat HCl 150 mg	10

Overall pain: Status Same

Group	Value	95% CI
Migalastat HCl 150 mg	8

Number Of Participants Who Experienced Sudden Onset Of Pain As Assessed Using The Fabry-Specific Pediatric Health And Pain Questionnaire (FPHPQ) Secondary · Month 12

The assessment of "In the last 3 months how many times did you experience sudden onset of pain?" using the FPHPQ for ages 13 to 18 is presented.

0 times

Group	Value	95% CI
Migalastat HCl 150 mg	4

1-3 times

Group	Value	95% CI
Migalastat HCl 150 mg	5

4-6 times

Group	Value	95% CI
Migalastat HCl 150 mg	4

> 6 times

Group	Value	95% CI
Migalastat HCl 150 mg	3

Change From Baseline In FPHPQ Score For Pain Intensity Secondary · Baseline, Month 12 and last observation (up to Month 12)

The assessment of "How bad is your pain today?" using the FPHPQ for ages 13 to 18 is presented. Pain intensity was measured on a 10-point scale, 0 (no pain) to 10 (pain as bad as you can imagine). A decrease from baseline indicates an improvement in the condition.

Month 12

Group	Value	95% CI
Migalastat HCl 150 mg	0.4	± 1.82

Last observation (up to Month 12)

Group	Value	95% CI
Migalastat HCl 150 mg	0.4	± 1.77

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Migalastat HCl 150 mg

Serious: 1/21 (5%)

Deaths: 0/21

Serious adverse events (1 terms)

Reaction	System	Migalastat HCl 150 mg
Suicidal ideation	Psychiatric disorders	—

Other adverse events (10 terms — click to expand)

Reaction	System	Migalastat HCl 150 mg
Upper respiratory tract infection	Infections and infestations	—
Influenza	Infections and infestations	—
Nasopharyngitis	Infections and infestations	—
Back pain	Musculoskeletal and connective tissue disorders	—
Headache	Nervous system disorders	—
Vomiting	Gastrointestinal disorders	—
Complication associated with device	General disorders	—
Pharyngitis streptococcal	Infections and infestations	—
Paraesthesia	Nervous system disorders	—
Rash	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Suicidal ideation.

Data from ClinicalTrials.gov NCT03500094 adverse events section.

Sponsor's own description

This was an open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric participants 12 to \<18 years of age with Fabry disease and amenable gene encoding α-galactosidase A (GLA) variants.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Safety and efficacy of migalastat in adolescent patients with Fabry disease: Results from ASPIRE, a phase 3b, open-label, single-arm, 12-month clinical trial, and its open-label extension.
   Ramaswami U, Font-Montgomery E, Goker-Alpan O, Ortiz D, et al · · 2025 · cited 3× · PMID 40215726 · DOI 10.1016/j.ymgme.2025.109102