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    Clinical Trial Results:
    An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients with Type 1 Gaucher Disease

    Summary
    EudraCT number
    		 2008-001965-27
    Trial protocol
    		 GB   ES  
    Global end of trial date
    28 Dec 2012

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Sep 2018
    First version publication date
    20 Mar 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    HGT-GCB-044
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00635427
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Shire Human Genetic Therapies (HGT), Inc.
    Sponsor organisation address
    300 Shire Way, Lexington, MA, United States, 02421
    Public contact
    MedInfo, Shire, +1 8668880660, US_ShireHGT_Medicalinformation@shire.com
    Scientific contact
    MedInfo, Shire, +1 8668880660, US_ShireHGT_Medicalinformation@shire.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000556-PIP01-09
    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 Dec 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this Phase III clinical study was to evaluate the long-term safety of velaglucerase alfa when administered every other week (EOW) intravenously (IV) in subjects with type 1 Gaucher disease.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice (GCP) and applicable regulatory requirements. Known instances of non-conformance were documented and are not considered to have had an impact on the overall conclusions of this study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Mar 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Tunisia: 9
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Russian Federation: 7
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Paraguay: 16
    Country: Number of subjects enrolled
    Israel: 18
    Country: Number of subjects enrolled
    India: 7
    Country: Number of subjects enrolled
    United States: 21
    Country: Number of subjects enrolled
    Argentina: 3
    Worldwide total number of subjects
    95
    EEA total number of subjects
    13
    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)
    13
    Adolescents (12-17 years)
    11
    Adults (18-64 years)
    68
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The first subject was enrolled in the study on 13 March 2008 and the last subject completed study procedures on 28 December 2012.

    Pre-assignment
    Screening details
    		 -

    Pre-assignment period milestones
    Number of subjects started
    		 95
    Intermediate milestone: Number of subjects
    Intent-to-treat (ITT) population: 93
    Intermediate milestone: Number of subjects
    Safety population: 95
    Number of subjects completed
    		 93

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Did not have type 1 Gaucher disease: 2
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032)
    Arm description
    		 VPRIV 45 units per kilogram (U/kg), IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    VPRIV®, Gene-Activated Human Glucocerebrosidase (GA-GCB)
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    VPRIV 45 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044.

    Arm title
    		 VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032)
    Arm description
    		 VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    VPRIV®, Gene-Activated Human Glucocerebrosidase (GA-GCB)
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27).

    Arm title
    		 VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)
    Arm description
    		 VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    VPRIV®, Gene-Activated Human Glucocerebrosidase (GA-GCB)
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).

    Arm title
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039)
    Arm description
    		 Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21) and switched to 60 U/kg VPRIV in HGT-GCB-044.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    VPRIV®, Gene-Activated Human Glucocerebrosidase (GA-GCB)
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21) and switched 60 U/kg VPRIV in HGT-GCB-044.

    Arm title
    		 VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034)
    Arm description
    		 VPRIV 15-60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647, 2006-006304-11) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    VPRIV®, Gene-Activated Human Glucocerebrosidase (GA-GCB)
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    VPRIV 15-60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647, 2006-006304-11) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034.

    Number of subjects in period 1 [1]
    		VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039) VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034)
    Started
    12
    11
    16
    16
    38
    Completed
    1
    6
    5
    7
    30
    Not completed
    11
    5
    11
    9
    8
         Consent withdrawn by subject
    -
    -
    -
    2
    2
         Death
    -
    -
    -
    1
    -
         'Refusal of required diagnostic evaluation '
    -
    -
    1
    -
    -
         Termination of study by sponsor
    11
    5
    10
    6
    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: Two subjects who did not have type 1 Gaucher disease were withdrawn from the ITT population as per statistical analysis plan (SAP) definition and removed from the long-term efficacy analyses in this study, needed to support the interpretation of the long-term efficacy results. Hence, 93 of 95 enrolled subjects worldwide were included in the baseline period which consisted of HGT-GCB-044 ITT population.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032)
    Reporting group description
    		 VPRIV 45 units per kilogram (U/kg), IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044.

    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032)
    Reporting group description
    		 VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27).

    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)
    Reporting group description
    		 VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).

    Reporting group title
    VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039)
    Reporting group description
    		 Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21) and switched to 60 U/kg VPRIV in HGT-GCB-044.

    Reporting group title
    VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034)
    Reporting group description
    		 VPRIV 15-60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647, 2006-006304-11) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034.

    Reporting group values
    		 VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039) VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) Total
    Number of subjects
    		 12 11 16 16 38 93
    Age categorical
    ITT population included all enrolled subjects who had type 1 Gaucher disease. Age at the time the informed consent was obtained in the core study.
    Units: Subjects
        At least 18 years
    		 2 3 3 5 9 22
        Between 18 and 65 years
    		 10 8 13 11 26 68
        Greater than or equal to 65 years
    		 0 0 0 0 3 3
    Age continuous
    ITT population. Age at the time the informed consent was obtained in the core study.
    Units: years
        arithmetic mean (standard deviation)
    		 32.5 ± 16.75 22 ± 11.08 32.9 ± 16.14 25 ± 17.33 34.3 ± 17.94 -
    Gender categorical
    ITT population.
    Units: Subjects
        Female
    		 7 6 8 7 18 46
        Male
    		 5 5 8 9 20 47
    Splenectomy status
    ITT population.
    Units: Subjects
        Yes
    		 0 0 9 10 3 22
        No
    		 12 11 7 6 35 71
    Baseline hemoglobin concentration per treatment group
    ITT population. Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039).
    Units: gram per deciliter
        arithmetic mean (full range (min-max))
    		 10.68 (8.5 to 12.9) 10.68 (7.1 to 12.3) 11.56 (9.7 to 14.4) 10.58 (8.1 to 13.1) 13.82 (10.7 to 16.5) -
    Baseline platelet counts per treatment group
    ITT population. Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039).
    Units: x10^9/L
        arithmetic mean (full range (min-max))
    		 69.3 (13 to 146) 79.4 (47 to 139) 160.1 (44 to 310) 186.3 (63 to 430) 165.4 (29 to 399) -
    Baseline liver volume per treatment group
    ITT population. Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039). Normal liver volume is defined as 2.5 percent of body weight.
    Units: Percent (%) body weight
        arithmetic mean (full range (min-max))
    		 1.64 (1.1 to 2.9) 1.63 (1 to 3.2) 1.59 (0.8 to 2.2) 1.68 (0.7 to 2.8) 0.82 (0.6 to 1.3) -
    Baseline Spleen volume per treatment group
    ITT population. Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HT-GCB-039). Normal spleen volume is defined as 0.2 percentage of body weight.
    Units: Multiple of Normal (MN)
        arithmetic mean (full range (min-max))
    		 23.08 (4.8 to 65.1) 18.48 (5.7 to 36.9) 12.69 (7.2 to 31.6) 23.52 (3.1 to 44.4) 4.1 (1.2 to 15.8) -

    End points

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    End points reporting groups
    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032)
    Reporting group description
    		 VPRIV 45 units per kilogram (U/kg), IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044.

    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032)
    Reporting group description
    		 VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27).

    Reporting group title
    VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)
    Reporting group description
    		 VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).

    Reporting group title
    VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039)
    Reporting group description
    		 Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21) and switched to 60 U/kg VPRIV in HGT-GCB-044.

    Reporting group title
    VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034)
    Reporting group description
    		 VPRIV 15-60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647, 2006-006304-11) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034.

    Subject analysis set title
    VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes subjects from the following groups: VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).

    Primary: Overall Summary of Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Overall Summary of Treatment Emergent Adverse Events (TEAEs) [1] [2]
    End point description
    Safety was evaluated by an analysis of adverse events (AEs), concomitant medication use, clinical laboratory tests, vital signs during the infusion of study drug, physical examination, and the development of anti-velaglucerase alfa. No formal comparisons or statistical tests were applied for the safety analyses, including for differences between the groups. All subjects who received at least 1 infusion (full or partial) of study drug were evaluated for safety (that is, were included in the safety population). There were 95 subjects in the safety population.
    End point type
    Primary
    End point timeframe
    Baseline to termination of study
    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: Inferential statistical analysis was not planned for this endpoint. Only descriptive statistics were reported.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A subject analysis set "VPRIV 60 U/kg (Parent Study VPRIV(45 or 60 U/kg) TKT032, GCB039)" was created by combining 3 reporting groups [VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)] of the baseline period and reported statistics for this endpoint as planned.
    End point values
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Number of subjects analysed
    16
    38
    41
    Units: Subjects
        Experienced no AEs
    1
    3
    3
        Experienced at least 1 AE
    15
    35
    38
        Experienced at least 1 drug-related (DR) AE
    7
    8
    9
        Experienced at least 1 infusion-related AE
    1
    5
    5
        Experienced at least 1 severe AE
    3
    4
    4
        Experienced at least 1 DR severe AE
    0
    0
    0
        Experienced at least 1 Life-threatening AE
    0
    0
    0
        Experienced at least 1 DR Life-threatening AE
    0
    0
    0
        Experienced at least 1 serious AE
    4
    6
    6
        Experienced at least 1 DR serious AE
    0
    0
    0
        Discontinued due to an AE
    0
    0
    0
        Deaths
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group

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    End point title
    		 Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group [3]
    End point description
    ITT population included all enrolled subjects who had type 1 Gaucher disease.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 months
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A subject analysis set "VPRIV 60 U/kg (Parent Study VPRIV(45 or 60 U/kg) TKT032, GCB039)" was created by combining 3 reporting groups [VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)] of the baseline period and reported statistics for this endpoint as planned.
    End point values
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Number of subjects analysed
    16
    38
    39
    Units: gram per deciliter
        arithmetic mean (confidence interval 95%)
    2 (1.25 to 2.75)
    -0.05 (-0.34 to 0.25)
    2.75 (2.28 to 3.22)
    No statistical analyses for this end point

    Secondary: Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group

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    End point title
    		 Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group [4]
    End point description
    ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 months
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A subject analysis set "VPRIV 60 U/kg (Parent Study VPRIV(45 or 60 U/kg) TKT032, GCB039)" was created by combining 3 reporting groups [VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)] of the baseline period and reported statistics for this endpoint as planned.
    End point values
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Number of subjects analysed
    16
    38
    39
    Units: 10^9 per liter
        arithmetic mean (confidence interval 95%)
    160.94 (117.22 to 204.66)
    9.03 (-2.6 to 20.66)
    87.85 (72.69 to 103)
    No statistical analyses for this end point

    Secondary: Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group

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    End point title
    		 Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group [5]
    End point description
    ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 months
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A subject analysis set "VPRIV 60 U/kg (Parent Study VPRIV(45 or 60 U/kg) TKT032, GCB039)" was created by combining 3 reporting groups [VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)] of the baseline period and reported statistics for this endpoint as planned.
    End point values
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Number of subjects analysed
    16
    38
    39
    Units: Percent (%) Body weight
        arithmetic mean (confidence interval 95%)
    -1.688 (-2.164 to -1.211)
    -0.026 (-0.1 to 0.047)
    -1.206 (-1.501 to -0.912)
    No statistical analyses for this end point

    Secondary: Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group

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    End point title
    		 Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group [6]
    End point description
    ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 months
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A subject analysis set "VPRIV 60 U/kg (Parent Study VPRIV(45 or 60 U/kg) TKT032, GCB039)" was created by combining 3 reporting groups [VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032); VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039)] of the baseline period and reported statistics for this endpoint as planned.
    End point values
    		 VPRIV 60 U/kg (Parent Study imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg)-TKT034) VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039)
    Number of subjects analysed
    16
    38
    39
    Units: Percent (%) change
        arithmetic mean (confidence interval 95%)
    -63.82 (-89.65 to -37.98)
    -8.04 (-14 to -2.08)
    -64.49 (-69.26 to -59.73)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    TEAEs were defined as AEs which occurred on or after the time of the first infusion in HGT-GCB-044, until 30 days after the subject's last study infusion
    Adverse event reporting additional description
    AEs may have been discovered through observation or examination of the subject, questioning of the subject, complaint by the subject, or by an abnormal clinical laboratory value. Severity of AEs was to be assessed by the investigator and recorded on the electronic case report form regardless of the severity or relationship to study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
    Reporting group description
    		 VPRIV 15-60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647, 2006-006304-11) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034.

    Reporting group title
    VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039)
    Reporting group description
    		 Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21) and switched to 60 U/kg VPRIV in HGT-GCB-044.

    Reporting group title
    VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)
    Reporting group description
    		 This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes subjects from the following groups: VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (2008-001965-27) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631, 2007-002840-21).

    Serious adverse events
    		 VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 38 (15.79%)
    4 / 16 (25.00%)
    6 / 41 (14.63%)
         number of deaths (all causes)
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign renal neoplasm
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Lower limb fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oligohydramnios
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Splenomegaly
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-Cardiac chest pain
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 16 (12.50%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchopneumonia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    35 / 38 (92.11%)
    15 / 16 (93.75%)
    35 / 41 (85.37%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lentigo
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    2
    0
    1
    Hypertension
         subjects affected / exposed
    4 / 38 (10.53%)
    0 / 16 (0.00%)
    5 / 41 (12.20%)
         occurrences all number
    6
    0
    6
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Fatigue
         subjects affected / exposed
    7 / 38 (18.42%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    8
    0
    3
    Chest discomfort
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Gait disturbance
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    6 / 41 (14.63%)
         occurrences all number
    2
    1
    10
    Reproductive system and breast disorders
    Galactorrhoea
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 38 (13.16%)
    3 / 16 (18.75%)
    0 / 41 (0.00%)
         occurrences all number
    6
    4
    0
    Dysphonia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    2
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    0
    Pharyngolaryngeal pain
         subjects affected / exposed
    5 / 38 (13.16%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    8
    0
    4
    Postnasal drip
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    4 / 41 (9.76%)
         occurrences all number
    0
    0
    5
    Rhinitis allergic
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    3
    1
    Sinus congestion
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    0
    Tachypnoea
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    2
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    2
    0
    3
    Blood urine present
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Haemoglobin decreased
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Mean cell volume increased
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Red blood cell count decreased
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Red blood cells urine positive
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    White blood cells urine positive
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    2
    1
    0
    Injury, poisoning and procedural complications
    Anaemia postoperative
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Burns first degree
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    0
    5
    Contusion
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    2
    1
    0
    Excoriation
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Injury
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    0
    1
    2
    Joint injury
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Procedural pain
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    6
    0
    0
    Skin laceration
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    3 / 41 (7.32%)
         occurrences all number
    0
    3
    3
    Drop attacks
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    6 / 38 (15.79%)
    4 / 16 (25.00%)
    7 / 41 (17.07%)
         occurrences all number
    10
    6
    16
    Hypoaesthesia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    2
    3
    2
    Sciatica
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Leukocytosis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphadenitis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Splenomegaly
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    0
    3
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Dry eye
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    3 / 41 (7.32%)
         occurrences all number
    2
    1
    3
    Abdominal pain upper
         subjects affected / exposed
    3 / 38 (7.89%)
    2 / 16 (12.50%)
    4 / 41 (9.76%)
         occurrences all number
    4
    2
    6
    Diarrhoea
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    2
    1
    3
    Dyspepsia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    4
    0
    3
    Rectal haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Toothache
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 16 (12.50%)
    6 / 41 (14.63%)
         occurrences all number
    3
    2
    7
    Vomiting
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    2
    0
    1
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Cholelithiasis
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 16 (12.50%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Cytolytic hepatitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    0
    6
    Liver disorder
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Dermatitis contact
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Erythema
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rash vesicular
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    7
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    9 / 38 (23.68%)
    2 / 16 (12.50%)
    14 / 41 (34.15%)
         occurrences all number
    13
    34
    33
    Arthritis
         subjects affected / exposed
    1 / 38 (2.63%)
    2 / 16 (12.50%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Back pain
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 16 (6.25%)
    5 / 41 (12.20%)
         occurrences all number
    7
    1
    6
    Bone pain
         subjects affected / exposed
    7 / 38 (18.42%)
    2 / 16 (12.50%)
    7 / 41 (17.07%)
         occurrences all number
    12
    7
    20
    Myalgia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    3
    0
    3
    Muscle spasms
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Osteoarthritis
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    3
    0
    1
    Pain in extremity
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 16 (6.25%)
    5 / 41 (12.20%)
         occurrences all number
    6
    1
    6
    Shoulder pain
         subjects affected / exposed
    3 / 38 (7.89%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    4
    2
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    5 / 41 (12.20%)
         occurrences all number
    1
    1
    13
    Bronchitis acute
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    5 / 41 (12.20%)
         occurrences all number
    0
    1
    5
    Dental caries
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Diarrhoea infectious
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 16 (6.25%)
    7 / 41 (17.07%)
         occurrences all number
    2
    1
    10
    Hepatitis a
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    1
    1
    3
    Influenza
         subjects affected / exposed
    4 / 38 (10.53%)
    4 / 16 (25.00%)
    6 / 41 (14.63%)
         occurrences all number
    6
    12
    10
    Nasopharyngitis
         subjects affected / exposed
    16 / 38 (42.11%)
    3 / 16 (18.75%)
    11 / 41 (26.83%)
         occurrences all number
    31
    4
    20
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    5 / 38 (13.16%)
    1 / 16 (6.25%)
    2 / 41 (4.88%)
         occurrences all number
    11
    1
    2
    Pyelonephritis acute
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    2 / 16 (12.50%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    0
    Rhinitis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    3 / 41 (7.32%)
         occurrences all number
    0
    1
    3
    Sinusitis
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    0
    Tinea versicolour
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    4 / 41 (9.76%)
         occurrences all number
    0
    2
    13
    Staphylococcal infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Tonsillitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 16 (0.00%)
    4 / 41 (9.76%)
         occurrences all number
    1
    0
    4
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 38 (23.68%)
    6 / 16 (37.50%)
    4 / 41 (9.76%)
         occurrences all number
    9
    14
    7
    Urinary tract infection
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    5
    0
    5
    Vaginal infection
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    3
    0
    1
    Varicella
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 16 (6.25%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 16 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    2
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Oct 2008
    Amendment 1 was revised from the original version to update the background information and contact information for serious adverse event reporting, and included several clarifications. The major clarification was that subjects completing TKT034 were permitted to continue to receive home infusions or were able to begin home infusions at any time.

    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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