Open-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease

Study Overview
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Brief Summary
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This is an open-label extension study intended to provide continued treatment with migalastat hydrochloride (HCl) for participants with Fabry disease who completed treatment of a previous migalastat HCl study. The study assessed the long-term safety and effectiveness of migalastat HCl.

Official Title
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An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: migalastat HCl 150 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant had completed treatment in a previous study of migalastat HCl given as a monotherapy Male and female participant agreed to use protocol-identified acceptable contraception Participant was willing to provide written informed consent and authorization for use and disclosure of Personal Health Information (PHI) Exclusion Criteria: Participant's last available estimated glomerular filtration rate (eGFR) in the previous study was <30 milliliter (mL)/minute (min)/1.73 meters squared (m^2); unless there was measured GFR available within 3 months of Baseline Visit, which was >30 mL/min/1.73 m^2 Participant had undergone, or was scheduled to undergo kidney transplantation or was currently on dialysis Participant had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before Baseline Visit Participant had clinically significant unstable cardiac disease in the opinion of the investigator (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association class III or IV congestive heart failure) Participant had a history of allergy or sensitivity to AT1001 (including excipients) or other iminosugars (for example, miglustat, miglitol) Participant required treatment with Glyset® (miglitol) or Zavesca® (miglustat) Participants with severe or unsuitable concomitant medical condition Participants with clinically significant abnormal laboratory value(s) and/or clinically significant electrocardiogram (ECG) findings

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Migalastat HCl 150 mg<br>Migalastat HCl 150 milligram (mg). | Drug: migalastat HCl 150 mg<br>* Migalastat HCl 150 mg (equivalent to 123 mg migalastat) was provided as capsules in blister packs. One capsule was taken orally every other day.<br>* Other names: Galafold;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Experiencing Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at time of reporting; visits typically occurred every 6 months. Serious AEs were life threatening or resulted in death, resulted in disability/incapacity, hospitalization or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: awareness of sign or symptom, does not interfere with normal everyday activities; Moderate: discomforting, interferes with normal everyday activities, but able to function; Severe: incapacitating, prevents normal everyday activities or significantly affects clinical status and requires medical intervention. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Day 1 after first dose to approximately 30 days after last treatment, median duration of 3.1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR) | The annualized rate of change in the eGFR was assessed per participant by the slope of the simple linear regression between the observed values and the assessment times. It was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR [CKD-EPI]) and the Modification of Diet in Renal Disease (MDRD) equation (eGFR [MDRD]). The equations are as follows: eGFR [MDRD] = 175 × (1/Serum Creatinine in mg/deciliter^1.154) × (1/Age in years^0.203) × 0.742 [if female] × 1.212 [if black] × 0.808 [if Japanese]; eGFR [CKD-EPI] = 141 × min(Serum creatinine [Scr]/k, 1)α × max(Scr/k, 1) - 1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black], where Scr is serum creatinine, k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1. Participants with at least a Baseline and a post-Baseline value are presented. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In eGFR At End Of Study | The change from baseline in eGFR was calculated using eGFR[CKD-EPI] and eGFR[MDRD] equations. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In Plasma Globotriaosylsphingosine (Lyso-Gb3) To End Of Study | Concentrations of lyso-Gb3 were measured in plasma using a qualified assay. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In White Blood Cell α-Gal A Activity To End Of Study | The activity of the α-galactosidase A (α-Gal A) enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Results for male participants are reported. Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In 24-hour Urine Protein To End Of Study | A 24-hour urine sample was collected to measure 24-hour urine protein. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In Left Ventricular Mass (LVM) To End Of Study | LVM was measured by echocardiography. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In Left Ventricular Mass Index (LVMi) To End Of Study | LVMi was measured by echocardiography. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 
| Change From Baseline In Patient Reported Quality Of Life To End Of Study, As Assessed By The Short Form-36 (SF-36) Questionnaire | The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health). Scores on each item are summed and averaged (range: 0=worst to 100=best). Scores were normed to the US population. Higher score indicates less disability. A positive change from baseline indicates improvement. Baseline was defined as the data collected in the last visit of the previous (feeder) study. Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis. | Baseline to approximately 30 days after last treatment, median duration of 3.1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amicus Therapeutics, Galafold, Migalastat, AT1001