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    Clinical Trial Results:
    A Randomized, Open-Label Study to Compare the Efficacy and Safety of AT1001 and Enzyme Replacement Therapy (ERT) in Patients With Fabry Disease and AT1001-Responsive GLA Mutations, Who Were Previously Treated With ERT.

    Summary
    EudraCT number
    		 2010-022636-37
    Trial protocol
    		 BE   GB   DK   AT   GR   DE   IT  
    Global end of trial date
    28 May 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Jul 2016
    First version publication date
    08 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AT1001-012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01218659
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amicus Therapeutics, Inc.
    Sponsor organisation address
    1 Cedarbrook Drive, Cranbury, United States, NJ 08512
    Public contact
    Medical Information, Amicus Therapeutics, Inc., MedInfo_Amicus@quintiles.com
    Scientific contact
    Medical Information, Amicus Therapeutics, Inc., MedInfo_Amicus@quintiles.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 May 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 May 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    28 May 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study was to compare the efficacy and safety of migalastat hydrochloride (migalastat HCl) to ERT in subjects with Fabry disease who were currently receiving ERT and who had migalastat-responsive alpha-galactosidase A gene (GLA) mutations.
    Protection of trial subjects
    This study was designed and monitored in accordance with sponsor procedures, which comply with the ethical principles of Good Clinical Practice, as required by the major regulatory authorities and in accordance with the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 Current approved therapy for Fabry disease is ERT consisting of lifelong biweekly intravenous infusion with 1 of 2 synthetic enzymes (agalsidase alfa or agalsidase beta) to treat the deficiency of the lysosomal enzyme alpha-galactosidase A (α-Gal A).
    Actual start date of recruitment
    08 Sep 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Brazil: 1
    Country: Number of subjects enrolled
    Denmark: 13
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Japan: 7
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    United States: 19
    Worldwide total number of subjects
    68
    EEA total number of subjects
    34
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    61
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 68 subjects were enrolled in this 2 period study. Subjects attended 25 study centres in 10 countries. First subject enrolled: 8 September 2011. Last subject completed: 28 May 2015. Period 1 was an 18-month randomized treatment period; Period 2 was an optional 12 month OLE.

    Pre-assignment
    Screening details
    		 Subjects with Fabry disease who were previously treated with ERT for at least 12 months and with known GLA mutations were enrolled. 60 subjects were randomized, 36 to the migalastat group and 24 to the ERT group (Period 1). The first dose of migalastat was given at Visit 2, 10 to 18 days after the last ERT infusion in the screening period.

    Pre-assignment period milestones
    Number of subjects started
    		 68
    Number of subjects completed
    		 60

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screen Failure: 8
    Period 1
    Period 1 title
    Period 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Migalastat-Migalastat
    Arm description
    		 During Period 1 (18-month randomized treatment period), subjects received migalastat HCl 150 milligram (mg) orally every other day (QOD) at approximately the same time. Inactive reminder capsules were taken on alternate days during each treatment period. During Period 2 (optional 12-month open-label extension [OLE]) all subjects received migalastat HCl 150 mg orally. Subjects were required to fast 2 hours before and 2 hours after each dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Migalastat HCl
    Investigational medicinal product code
    AT1001
    Other name
    Migalastat
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg of migalastat HCl was administered orally QOD at approximately the same time each day. Subjects were required to fast 2 hours before and 2 hours after taking each dose of migalastat.

    Arm title
    		 ERT-Migalastat
    Arm description
    		 During Period 1 (18-month randomized treatment period), subjects continued to receive at least 80% of the currently labelled dose and regimen of ERT (agalsidase alfa or agalsidase beta) as an intravenous infusion and as prescribed by the subject's treating physician. The dose level and regimen of ERT were required to be stable for the 3 months prior to the baseline visit. During Period 2 (optional 12-month OLE) all subjects received migalastat HCl 150 mg orally.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    ERT
    Investigational medicinal product code
    ERT
    Other name
    Agalsidase
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Agalsidase alfa or agalsidase beta was administered as an intravenous infusion in accordance with the prescibing information of the treating physician. Subjects were required to fast 2 hours before and 2 hours after taking each dose.

    Number of subjects in period 1 [1]
    		Migalastat-Migalastat ERT-Migalastat
    Started
    36
    24
    Completed
    34
    18
    Not completed
    2
    6
         Consent withdrawn by subject
    2
    6
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of subjects starting the baseline period includes all subjects who met the eligibility criteria for the study and is equivalent to the number of subjects completing the pre-assignment period.
    Period 2
    Period 2 title
    Period 2
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Migalastat-Migalastat
    Arm description
    		 During Period 1 (18-month randomized treatment period), subjects received migalastat HCl 150 milligram (mg) orally every other day (QOD) at approximately the same time. Inactive reminder capsules were taken on alternate days during each treatment period. During Period 2 (optional 12-month open-label extension [OLE]) all subjects received migalastat HCl 150 mg orally. Subjects were required to fast 2 hours before and 2 hours after each dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Migalastat HCl
    Investigational medicinal product code
    AT1001
    Other name
    Migalastat
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg of migalastat HCl was administered orally QOD at approximately the same time each day. Subjects were required to fast 2 hours before and 2 hours after taking each dose of migalastat.

    Arm title
    		 ERT-Migalastat
    Arm description
    		 During Period 1 (18-month randomized treatment period), subjects continued to receive at least 80% of the currently labelled dose and regimen of ERT (agalsidase alfa or agalsidase beta) as an intravenous infusion and as prescribed by the subject's treating physician. The dose level and regimen of ERT were required to be stable for the 3 months prior to the baseline visit. During Period 2 (optional 12-month OLE) all subjects received migalastat HCl 150 mg orally.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Migalastat HCl
    Investigational medicinal product code
    AT1001
    Other name
    Migalastat
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg of migalastat HCl was administered orally QOD at approximately the same time each day. Subjects were required to fast 2 hours before and 2 hours after taking each dose of migalastat.

    Number of subjects in period 2 [2]
    		Migalastat-Migalastat ERT-Migalastat
    Started
    33
    15
    Completed
    30
    12
    Not completed
    3
    3
         Consent withdrawn by subject
    1
    1
         Physician decision
    -
    1
         Pregnancy
    1
    -
         Lost to follow-up
    -
    1
         Lack of efficacy
    1
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Period 2 of the Study was an optional 12-month open-label extension. As such not all subjects who completed Period 1 entered Period 2.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Migalastat-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects received migalastat HCl 150 milligram (mg) orally every other day (QOD) at approximately the same time. Inactive reminder capsules were taken on alternate days during each treatment period. During Period 2 (optional 12-month open-label extension [OLE]) all subjects received migalastat HCl 150 mg orally. Subjects were required to fast 2 hours before and 2 hours after each dose.

    Reporting group title
    ERT-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects continued to receive at least 80% of the currently labelled dose and regimen of ERT (agalsidase alfa or agalsidase beta) as an intravenous infusion and as prescribed by the subject's treating physician. The dose level and regimen of ERT were required to be stable for the 3 months prior to the baseline visit. During Period 2 (optional 12-month OLE) all subjects received migalastat HCl 150 mg orally.

    Reporting group values
    		 Migalastat-Migalastat ERT-Migalastat Total
    Number of subjects
    		 36 24 60
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 32 21 53
        From 65-84 years
    		 4 3 7
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.5 ± 13.76 44.9 ± 14.47 -
    Gender Categorical
    Units: Subjects
        Male
    		 16 10 26
        Female
    		 20 14 34

    End points

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    End points reporting groups
    Reporting group title
    Migalastat-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects received migalastat HCl 150 milligram (mg) orally every other day (QOD) at approximately the same time. Inactive reminder capsules were taken on alternate days during each treatment period. During Period 2 (optional 12-month open-label extension [OLE]) all subjects received migalastat HCl 150 mg orally. Subjects were required to fast 2 hours before and 2 hours after each dose.

    Reporting group title
    ERT-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects continued to receive at least 80% of the currently labelled dose and regimen of ERT (agalsidase alfa or agalsidase beta) as an intravenous infusion and as prescribed by the subject's treating physician. The dose level and regimen of ERT were required to be stable for the 3 months prior to the baseline visit. During Period 2 (optional 12-month OLE) all subjects received migalastat HCl 150 mg orally.
    Reporting group title
    Migalastat-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects received migalastat HCl 150 milligram (mg) orally every other day (QOD) at approximately the same time. Inactive reminder capsules were taken on alternate days during each treatment period. During Period 2 (optional 12-month open-label extension [OLE]) all subjects received migalastat HCl 150 mg orally. Subjects were required to fast 2 hours before and 2 hours after each dose.

    Reporting group title
    ERT-Migalastat
    Reporting group description
    		 During Period 1 (18-month randomized treatment period), subjects continued to receive at least 80% of the currently labelled dose and regimen of ERT (agalsidase alfa or agalsidase beta) as an intravenous infusion and as prescribed by the subject's treating physician. The dose level and regimen of ERT were required to be stable for the 3 months prior to the baseline visit. During Period 2 (optional 12-month OLE) all subjects received migalastat HCl 150 mg orally.

    Subject analysis set title
    Migalastat with amenable GLA mutations
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The migalastat with amenable GLA mutations modified Intent-to-Treat (mITT) population includes all randomized subjects with mutations amenable to migalastat in the Good Laboratory Practice Human Embryonic Kidney (GLP HEK) assay who received at least 1 dose of migalastat and who had relevant baseline and postbaseline efficacy measures.

    Subject analysis set title
    ERT with amenable GLA mutations
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The ERT with amenable GLA mutations mITT population includes all randomized subjects with mutations amenable to migalastat in the GLP HEK assay who received at least 1 dose of ERT and who had relevant baseline and postbaseline efficacy measures.

    Subject analysis set title
    Migalastat Safety Population (30-month analyses)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The migalastat safety population (30-month analyses) includes all subjects in the ITT population who received at least 1 dose of migalastat during Periods 1 and 2.

    Subject analysis set title
    ERT Safety Population (18-month analyses)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The ERT safety population (18-month analyses) includes all subjects in the ITT population who received at least 1 dose of ERT during Period 1.

    Primary: Estimated glomerular filtration rate (eGFR)

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    End point title
    		 Estimated glomerular filtration rate (eGFR) [1]
    End point description
    The annualized rate of change in eGFR is presented for subjects who received migalastat or ERT in Period 1. This was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR[CKD-EPI]) and was determined for subjects with GLA mutations amenable to migalastat in the validated GLP HEK assay. The calculated least squares (LS) means and confidence intervals (CIs) are based on an analysis of covariance (ANCOVA) model that includes the treatment groups, baseline eGFR[CKD-EPI], sex, age and baseline 24-hour urine protein stratification factor. The measure of comparability between migalastat and ERT in the annualized rate of change of primary efficacy parameters was defined as a >50% overlap of the 95% CIs and a difference of LS mean annualized rate of change no greater than 2.2 mL/min/1.73 m2.
    End point type
    Primary
    End point timeframe
    Baseline to Month 18
    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: The Study analyses were performed using descriptive statistics. No statistical inference testing was performed.
    End point values
    		 Migalastat with amenable GLA mutations ERT with amenable GLA mutations
    Number of subjects analysed
    34
    18
    Units: mL/min/1.73m2
        least squares mean (confidence interval 95%)
    -0.397 (-2.272 to 1.478)
    -1.031 (-3.636 to 1.575)
    No statistical analyses for this end point

    Secondary: Change from Baseline in left ventricular mass index (LVMi)

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    End point title
    		 Change from Baseline in left ventricular mass index (LVMi)
    End point description
    The cardiac parameter LVMi was measured by echocardiogram (ECHO) at Visits 2, 5, 7, 9, 12 and 13, and the ECHOs were read centrally in a blinded fashion. The change from Baseline to Month 18 is presented for subjects who received migalastat or ERT in Period 1.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 18
    End point values
    		 Migalastat with amenable GLA mutations ERT with amenable GLA mutations
    Number of subjects analysed
    34
    18
    Units: grams per square meter (g/m2)
        arithmetic mean (standard deviation)
    -6.578 ± 12.0817
    -2.015 ± 14.8569
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were reported from the first dose of study medication in Period 1 through to 30 days after the last treatment visit whether in Period 1 or Period 2.
    Adverse event reporting additional description
    AE data is reported as treatment-emergent AEs. AEs are presented for subjects in the safety population for both study periods, i.e. over 30 months. Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 and 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Migalastat Safety Population (30-month analyses)
    Reporting group description
    		 The migalastat safety population includes all subjects in the ITT population who received at least 1 dose of migalastat during Periods 1 and 2.

    Reporting group title
    ERT Safety Population (18-month analyses)
    Reporting group description
    		 The ERT safety population includes all subjects in the ITT population who received at least 1 dose of ERT during Period 1.

    Serious adverse events
    		 Migalastat Safety Population (30-month analyses) ERT Safety Population (18-month analyses)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 51 (31.37%)
    7 / 21 (33.33%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    PHAEOCHROMOCYTOMA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    CHEST PAIN
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE MALFUNCTION
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ATELECTASIS
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1). Event experienced by 1 subject in separate periods.
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMOPTYSIS
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1). Event experienced by 1 subject in separate periods.
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    SUICIDAL IDEATION
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    UPPER LIMB FRACTURE
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ATRIAL FIBRILLATION
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC FAILURE CHRONIC
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENTRICULAR TACHYCARDIA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    EMBOLIC STROKE
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOAESTHESIA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1). Event experienced by 1 subject in separate periods.
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    VERTIGO
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    VISION BLURRED
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERNIAL EVENTRATION
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1). Event experienced by 1 subject in separate periods.
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STONE
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    PROTEINURIA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    ENDOCARDITIS
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERINEAL ABSCESS
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    OBESITY
    Additional description: Reporting groups: Migalastat Safety Population (30-month analyses) (subjects received migalastat in Periods 1 + 2) and ERT Safety Population (18-month analyses) (subjects received ERT in Period 1).
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Migalastat Safety Population (30-month analyses) ERT Safety Population (18-month analyses)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    49 / 51 (96.08%)
    19 / 21 (90.48%)
    Investigations
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    7 / 51 (13.73%)
    0 / 21 (0.00%)
         occurrences all number
    8
    0
    PROTEIN URINE PRESENT
         subjects affected / exposed
    4 / 51 (7.84%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    Injury, poisoning and procedural complications
    FALL
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    5
    1
    PROCEDURAL PAIN
         subjects affected / exposed
    0 / 51 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    3
    Cardiac disorders
    PALPITATIONS
         subjects affected / exposed
    5 / 51 (9.80%)
    1 / 21 (4.76%)
         occurrences all number
    7
    1
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    8 / 51 (15.69%)
    2 / 21 (9.52%)
         occurrences all number
    12
    3
    HEADACHE
         subjects affected / exposed
    16 / 51 (31.37%)
    6 / 21 (28.57%)
         occurrences all number
    23
    6
    NEURALGIA
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    4
    1
    PARAESTHESIA
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    8
    0
    TREMOR
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    4
    0
    General disorders and administration site conditions
    FATIGUE
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    4
    1
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 21 (9.52%)
         occurrences all number
    3
    2
    PAIN
         subjects affected / exposed
    5 / 51 (9.80%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    PYREXIA
         subjects affected / exposed
    6 / 51 (11.76%)
    2 / 21 (9.52%)
         occurrences all number
    9
    4
    Ear and labyrinth disorders
    TINNITUS
         subjects affected / exposed
    5 / 51 (9.80%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    VERTIGO
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 21 (4.76%)
         occurrences all number
    3
    2
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    7 / 51 (13.73%)
    2 / 21 (9.52%)
         occurrences all number
    10
    2
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 21 (4.76%)
         occurrences all number
    5
    1
    CONSTIPATION
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    4
    1
    DIARRHOEA
         subjects affected / exposed
    11 / 51 (21.57%)
    2 / 21 (9.52%)
         occurrences all number
    13
    2
    DRY MOUTH
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 21 (9.52%)
         occurrences all number
    1
    2
    DYSPEPSIA
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 21 (4.76%)
         occurrences all number
    4
    1
    GASTRITIS
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 21 (9.52%)
         occurrences all number
    1
    2
    NAUSEA
         subjects affected / exposed
    8 / 51 (15.69%)
    2 / 21 (9.52%)
         occurrences all number
    10
    2
    TOOTHACHE
         subjects affected / exposed
    4 / 51 (7.84%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    VOMITING
         subjects affected / exposed
    8 / 51 (15.69%)
    3 / 21 (14.29%)
         occurrences all number
    9
    4
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    8 / 51 (15.69%)
    5 / 21 (23.81%)
         occurrences all number
    8
    5
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    4 / 51 (7.84%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    Skin and subcutaneous tissue disorders
    HYPERHIDROSIS
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    4
    2
    INSOMNIA
         subjects affected / exposed
    5 / 51 (9.80%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    6 / 51 (11.76%)
    2 / 21 (9.52%)
         occurrences all number
    12
    2
    BACK PAIN
         subjects affected / exposed
    5 / 51 (9.80%)
    4 / 21 (19.05%)
         occurrences all number
    6
    4
    MUSCLE SPASMS
         subjects affected / exposed
    4 / 51 (7.84%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    3 / 51 (5.88%)
    1 / 21 (4.76%)
         occurrences all number
    3
    1
    MYALGIA
         subjects affected / exposed
    6 / 51 (11.76%)
    1 / 21 (4.76%)
         occurrences all number
    10
    1
    NECK PAIN
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    3 / 51 (5.88%)
    2 / 21 (9.52%)
         occurrences all number
    6
    2
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    5 / 51 (9.80%)
    3 / 21 (14.29%)
         occurrences all number
    6
    5
    CYSTITIS
         subjects affected / exposed
    4 / 51 (7.84%)
    1 / 21 (4.76%)
         occurrences all number
    5
    1
    HERPES ZOSTER
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    INFLUENZA
         subjects affected / exposed
    12 / 51 (23.53%)
    4 / 21 (19.05%)
         occurrences all number
    15
    4
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 21 (0.00%)
         occurrences all number
    4
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    21 / 51 (41.18%)
    7 / 21 (33.33%)
         occurrences all number
    41
    11
    SINUSITIS
         subjects affected / exposed
    4 / 51 (7.84%)
    3 / 21 (14.29%)
         occurrences all number
    7
    3
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    5 / 51 (9.80%)
    2 / 21 (9.52%)
         occurrences all number
    6
    2
    URINARY TRACT INFECTION
         subjects affected / exposed
    6 / 51 (11.76%)
    1 / 21 (4.76%)
         occurrences all number
    8
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Apr 2011
    • Increase in number of sites to facilitate enrollment • Change in the randomization ratio of treatment with migalastat or ERT from 1:1 to 1.5:1 • Re-defined proteinuria parameter for subject randomization stratification to <0.1 g/24 h and ≥ 0.1 g/24 h • Medical specialist to be consulted for clinical outcomes • Informed consent to be completed prior to any study related procedures • Discontinued subjects to complete assessments at last treatment visit • Subjects to receive ERT at least ≥ 80% of currently labelled dose • Migalastat treatment to begin at least 5 days after last ERT infusion • Increased number of visits during OLE period from 2 to 4.
    27 Nov 2012
    • Removal of recruitment period extension in Japan • Addition of an optional repeat GLA genotype blood draw to help validate a new genotyping test under development • Update of pregnancy language • Addition of allowance to use future exploratory analyses with retained biological samples to improve understanding of Fabry disease • Periodic updates to be provided to regulatory authorities and ethics committees responsible for suspected, unexpected, serious adverse reactions.
    13 Mar 2013
    • Addition of a mechanism for subjects to transition to a separate protocol, early access or other program after completing both study treatment periods and removal of need to complete a follow-up visit if this was the case • Addition of a telephone contact to assess study drug compliance for subjects receiving migalastat • Addition of requirement for subjects to return for an unscheduled visit to draw an additional blood sample to measure α-Gal A activity • Addition of guidance regarding use of medication that inhibited the protein renin-angiotensin system or that could affect renal perfusion.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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