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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04049760

Enrollment

Registered

2019-08-08

Start date

2019-10-11

Completion date

2024-11-29

Last updated

2026-02-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fabry Disease

Keywords

Lysosomal disease, migalastat

Brief summary

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

Interventions

DRUGmigalastat HCl 150 mg

migalastat HCl 150 mg capsule

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

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 * If of reproductive potential, both male and female subjects agreed 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

* Subject's last available estimated glomerular filtration rate (eGFR) in the previous study was \< 60 mL/min/1.73 m2 * Subject had advanced kidney disease requiring dialysis or kidney transplantation * Subject received any investigational/experimental drug, biologic, or device within 30 days before baseline, with the exception of migalastat * Subject anticipated starting gene therapy during the study period * Subject had any intercurrent illness or condition at Visit 1 that may have precluded the subject from fulfilling the protocol requirements or suggested to the investigator that the potential subject may have an unacceptable risk by participating in this study * Subject had a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol) * Subject required treatment with Replagal® (agalsidase alfa) or Fabrazyme® (agalsidase beta) * Subject required treatment with Glyset® (miglitol) or Zavesca® (miglustat) * Female subject was pregnant or breast-feeding, or was planning to become pregnant during the study period * In the opinion of the investigator, the subject and/or parent or legally-authorized representative was unlikely or unable to comply with the study requirements

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs (Adverse Events) Leading to Discontinuation of Study Drug	Entire study	Number of subjects with TEAE, SAE, and AE leading to discontinuation during the study period

Secondary

Measure	Time frame	Description
Change From Baseline to Month 24 in Estimated Glomerular Filtration Rate (eGFR)	Baseline, Month 24	Estimated GFR was calculated using the modified Schwartz formula according to the standards of the central laboratory.
Change From Baseline to Month 24 in Urine Protein Levels	Baseline, Month 24	Renal function was assessed by urine protein levels (mg/L). Urine samples were collected as part of urinalysis.
Change From Baseline to Month 24 in Urine Albumin	Baseline, Month 24	Renal function was assessed by urine albumin levels (mg/L). Urine samples were collected as part of urinalysis
Change From Baseline to Month 24 in Left Ventricular Mass Index (LVMi)	Baseline, Month 24	LVMi was assessed as a measure of cardiac impairment in the study participants. LVMi values for both M-mode and 2D views are presented.
Change From Baseline to Month 24 in Pediatric and Quality of Life Inventory™ (PedsQL™) Scores	Baseline, Month 24	The Pediatric Quality of Life Inventory (PedsQL™) was a modular approach to measuring health-related quality of life (QoL) in healthy children and adolescents and those with acute and chronic health conditions. All components of the PedsQL were scored based on a scale of 0 (never) to 4 (almost always) and linearly transformed to a 0 to 100 scale as follows: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0. Psychosocial, physical, and total scores were calculated based on the response to the questions within the patient reported outcome. The psychosocial score for the PedsQL encompassed 15 questions relating to the subjects' feelings, social interaction with others, and school. The physical score was derived from answers to 8 questions about the subjects' ease of managing physical activity. Total scores were the sum of all the item scores over the number of items answered on all the scales. Change from baseline values of \<0 represents worsening, 0 equals no change, and \>0 represents improvement.
Change From Baseline to Month 24 in Fabry-Specific Pediatric Health and Pain Questionnaire (FPHPQ) Score for Pain Intensity	Baseline, Month 24	The Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ) included questions about Fabry disease-specific symptoms. The assessment of "How bad is your pain today?" was measured on a 10- point scale from 0 (no pain) to 10 (pain as bad as you can imagine). A decrease from baseline indicates an improvement in the condition.
Number of Subjects Who Experienced Sudden Onset of Pain As Assessed Using the Fabry-Specific Health and Pain Questionnaire (FPHPQ)	Month 24	Subjects were asked "In the last 3 months how many times did you experience sudden onset of pain?" and responses were reported in the FPHPQ. Responses were categorized as 0, 1 to 3, 4 to 6, and \> 6 occurrences of sudden onset of pain.
Change From Baseline to Month 24 in Plasma Levels of Lyso-Gb3	Baseline, Month 24	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.

Countries

United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Migalastat HCl 150 mg One migalastat 123 mg capsule (equivalent to 150 mg migalastat HCl) administered every other day (QOD) during the treatment period.	16
Total	16

Baseline characteristics

Characteristic	Migalastat HCl 150 mg
Age, Customized 12 to < 16 years	7 Participants
Age, Customized 16 to < 18 years	9 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Prior Enzyme Replacement Therapy (ERT) status ERT-experienced	8 Participants
Prior Enzyme Replacement Therapy (ERT) status ERT-naive	8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	15 Participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 16
other Total, other adverse events	13 / 16
serious Total, serious adverse events	1 / 16

Outcome results

Primary

Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs (Adverse Events) Leading to Discontinuation of Study Drug

Number of subjects with TEAE, SAE, and AE leading to discontinuation during the study period

Time frame: Entire study

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Migalastat HCl 150 mg	Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs (Adverse Events) Leading to Discontinuation of Study Drug	Number of subjects with TEAEs	13 Participants
Migalastat HCl 150 mg	Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs (Adverse Events) Leading to Discontinuation of Study Drug	Number of subjects with SAE	1 Participants
Migalastat HCl 150 mg	Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs (Adverse Events) Leading to Discontinuation of Study Drug	Number of subjects with AE leading to discontinuation	0 Participants

Secondary

Change From Baseline to Month 24 in Estimated Glomerular Filtration Rate (eGFR)

Estimated GFR was calculated using the modified Schwartz formula according to the standards of the central laboratory.