Clinical Trial Results:
An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects with Fabry Disease
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Summary
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EudraCT number |
2014-002701-38 |
Trial protocol |
AT BE GB ES DK |
Global end of trial date |
23 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Nov 2020
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First version publication date |
06 Nov 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AT1001-042
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02194985 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Amicus Therapeutics, Inc.
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Sponsor organisation address |
1 Cedar Brook Drive, Cranbury, NJ, United States, 08512
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Public contact |
Medical Affairs, Amicus Therapeutics, medinfo@amicusrx.com
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Scientific contact |
Medical Affairs, Amicus Therapeutics, medinfo@amicusrx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Oct 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess long-term safety of migalastat hydrochloride (HCl) in the treatment of participants with Fabry disease who have completed treatment in a previous study of migalastat HCl.
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which the study was conducted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Mar 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 1
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Country: Number of subjects enrolled |
Australia: 13
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Country: Number of subjects enrolled |
Brazil: 3
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Country: Number of subjects enrolled |
Egypt: 1
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Country: Number of subjects enrolled |
Japan: 5
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Country: Number of subjects enrolled |
Turkey: 3
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Country: Number of subjects enrolled |
United States: 25
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Country: Number of subjects enrolled |
Canada: 3
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
Austria: 2
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Denmark: 12
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
Italy: 3
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Worldwide total number of subjects |
84
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
72
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants entered this extension study immediately upon completion of their final treatment visit in a previous migalastat HCl study. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Migalastat HCl 150 mg | ||||||||||||||||||||
Arm description |
Migalastat HCl 150 milligram (mg) was administered orally once every other day for a median duration of 3.1 years (ranged from approximately 1 month to 4.3 years). | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Migalastat HCl 150 mg
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Investigational medicinal product code |
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Other name |
AT1001
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Migalastat HCl 150 mg (equivalent to 123 mg migalastat) was provided as capsules in blister packs. One capsule was taken orally every other day.
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Baseline characteristics reporting groups
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Reporting group title |
Overall
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Reporting group description |
All participants who took at least 1 dose of the study drug after they had enrolled into this study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Migalastat HCl 150 mg
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Reporting group description |
Migalastat HCl 150 milligram (mg) was administered orally once every other day for a median duration of 3.1 years (ranged from approximately 1 month to 4.3 years). | ||
Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.
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Subject analysis set title |
Intent-to-Treat Population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.
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End point title |
Number Of Participants Experiencing Adverse Events (AEs) [1] | ||||||||||||||||||||||||||
End point description |
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 Adverse Events section.
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End point type |
Primary
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End point timeframe |
Day 1 (after dosing) to End of Study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Quantitative statistical analysis was not performed for this end point; no treatment groups were compared in this single-group study. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR) | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [2] - Intent-to-Treat (ITT) Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline In eGFR At End Of Study | ||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [3] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change From Baseline In Plasma Globotriaosylsphingosine (Lyso-Gb3) To End Of Study | ||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [4] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline In White Blood Cell α-Gal A Activity To End Of Study | ||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [5] - Male participants in ITT population who had analyzable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline In 24-hour Urine Protein To End Of Study | ||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [6] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline In Left Ventricular Mass (LVM) To End Of Study | ||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [7] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline In Left Ventricular Mass Index (LVMi) To End Of Study | ||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [8] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline In Patient Reported Quality Of Life To End Of Study, As Assessed By The Short Form-36 (SF-36) Questionnaire | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, End of Study
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| Notes [9] - ITT population who had analysable data at the specified time points. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to up to 4.4 years (includes safety follow-up)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Migalastat HCl 150 mg
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Reporting group description |
Migalastat HCl 150 mg was administered orally once every other day for a median duration of 3.1 years (ranged from approximately 1 month to 4.3 years). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Oct 2015 |
• Revised the lowest age limit for enrollment from 16 to 18 years of age. The participants under the age of 18 were allowed to enroll at sites with required relevant regulatory and ethics approvals.
• Added a new stopping criterion: An eGFR value of < 30 mL/min/1.73 m^2.
• Removed a requirement to collect historical (up to 5-year) Fabry disease data from the participants.
• Revised contraception requirements for both male and female participants, clarifying that contraception methods must be medically accepted, and abstinence was not allowed.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None | |||
