Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42567   clinical trials with a EudraCT protocol, of which   7008   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Open-label, Multicenter, Single-arm, Phase 4 Study of the Effect of Treatment with Velaglucerase alfa on Bone-related Pathology in Treatment-naïve Patients with Type 1 Gaucher Disease

    Summary
    EudraCT number
    2015-001578-17
    Trial protocol
    GB   DE   ES   IT  
    Global end of trial date
    30 Nov 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Dec 2021
    First version publication date
    15 Dec 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    SHP-GCB-402
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02574286
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, United States, MA 02421
    Public contact
    Study Director, Shire, ClinicalTransparenc@takeda.com
    Scientific contact
    Study Director, Shire, ClinicalTransparenc@takeda.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
    30 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study is to evaluate the effect of velaglucerase alfa (VPRIV) therapy (60 units per kilogram [U/kg] every other week [EOW]) in treatment-naïve subjects with type 1 Gaucher disease on change from baseline in lumbar spine (LS) bone mineral density (BMD) Z-score as measured by dual energy x-ray absorptiometry (DXA) after 24 months of treatment.
    Protection of trial subjects
    The study was conducted in accordance with current applicable industry regulations, International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996) and any updates, European Union (EU) Directive 2001/20/EC and its updates, the ethical principles in the Declaration of Helsinki, and local ethical and legal requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Jun 2016
    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
    Israel: 12
    Country: Number of subjects enrolled
    United States: 4
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    United Kingdom: 3
    Worldwide total number of subjects
    21
    EEA total number of subjects
    2
    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)
    19
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study was conducted in the United States, Israel, Spain and United Kingdom from 07 June 2016 (first subjects first visit) to 30 November 2020 (last subjects last visit)

    Pre-assignment
    Screening details
    A total of 21 subjects were enrolled and received treatment in this study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Velaglucerase alfa 60 U/kg
    Arm description
    Subjects received 60-minute intravenous (IV) infusion of 60 U/kg velaglucerase alfa EOW for 24 months (up to 101 weeks).
    Arm type
    Experimental

    Investigational medicinal product name
    Velaglucerase alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 60-minute IV infusion of 60 U/kg velaglucerase alfa EOW for 24 months.

    Number of subjects in period 1
    Velaglucerase alfa 60 U/kg
    Started
    21
    Completed
    16
    Not completed
    5
         Withdrawal by Subject
    2
         Adverse event, non-fatal
    3

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Velaglucerase alfa 60 U/kg
    Reporting group description
    Subjects received 60-minute intravenous (IV) infusion of 60 U/kg velaglucerase alfa EOW for 24 months (up to 101 weeks).

    Reporting group values
    Velaglucerase alfa 60 U/kg Total
    Number of subjects
    21
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    43.9 ± 14.2 -
    Gender categorical
    Units: Subjects
        Female
    11 11
        Male
    10 10
    Race
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    0 0
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    0 0
        White
    20 20
        More than one race
    1 1
        Unknown or Not Reported
    0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0 0
        Not Hispanic or Latino
    19 19
        Unknown or Not Reported
    2 2

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Velaglucerase alfa 60 U/kg
    Reporting group description
    Subjects received 60-minute intravenous (IV) infusion of 60 U/kg velaglucerase alfa EOW for 24 months (up to 101 weeks).

    Primary: Change From Baseline in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103) [1]
    End point description
    BMD of the LS was measured by dual energy x-ray absorptiometry (DXA), and the result was converted to Z-scores appropriate for age, sex, and race. The Z-score indicated the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 was equal to the mean. Negative numbers indicated values lower than the mean and positive numbers indicated values higher than the mean. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in lumbar spine BMD Z-Score up to EOS (Week 103) was reported. Intent-to-Treat (ITT) Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline up to EOS (Week 103)
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    16
    Units: Z-score
        arithmetic mean (standard deviation)
    0.17 ± 0.394
    No statistical analyses for this end point

    Secondary: Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51

    Close Top of page
    End point title
    Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51
    End point description
    BMD of the LS was measured by DXA, and the results was converted to Z-scores appropriate for age, sex, and race. The Z-score indicated the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 was equal to the mean. Negative numbers indicated values lower than the mean and positive numbers indicated values higher than the mean. Baseline was defined as last data collected prior to the first administration of study drug. Change From baseline in LS BMD Z-score at Week 51 was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    16
    Units: Z-Score
        arithmetic mean (standard deviation)
    0.02 ± 0.431
    No statistical analyses for this end point

    Secondary: Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)
    End point description
    BMD of the LS was measured by dual energy x-ray absorptiometry (DXA), and the results was measured in gram per square centimeter (g/cm^2). Baseline was defined as last data collected prior to the first administration of study drug. Change From baseline in LS BMD at Week 51 and EOS (Week 103) was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    16
    Units: g/cm^2
    arithmetic mean (standard deviation)
        Change at Week 51
    0.006 ± 0.0342
        Change at EOS (Week 103)
    0.011 ± 0.0474
    No statistical analyses for this end point

    Secondary: Change From Baseline in Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)
    End point description
    BMB score was a semi-quantitative magnetic resonance imaging (MRI) scoring system for assessing the extent of bone marrow involvement in Gaucher disease. BMB scores was calculated from MRI of the LS and femurs with a range from 0 (no abnormalities) to 8 points (severe disease). A positive BMB score indicated more severe bone marrow involvement and negative BMB score indicated less severe bone marrow involvement. Baseline was defined as last data collected prior to the first administration of study drug. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    15
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Change at Week 51(n=15)
    -3.0 ± 1.85
        Change at EOS (Week 103) (n=13)
    -3.0 ± 2.27
    No statistical analyses for this end point

    Secondary: Change From Baseline in Hemoglobin Concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Hemoglobin Concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
    End point description
    Blood samples were collected for measurement of hemoglobin concentration. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in hemoglobin concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103) was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    18
    Units: grams per deciliter (g/dL)
    arithmetic mean (standard deviation)
        Change at Week 13 (n=17)
    0.532 ± 0.7624
        Change at Week 25 (n=18)
    0.764 ± 0.6688
        Change at Week 37 (n=17)
    0.765 ± 0.7836
        Change at Week 51 (n=17)
    0.935 ± 0.6588
        Change at Week 65 (n=17)
    1.029 ± 0.8239
        Change at Week 77 (n=13)
    1.015 ± 1.1577
        Change at Week 89 (n=13)
    1.138 ± 0.8910
        Change at Week EOS (Week 103) (n=18)
    0.897 ± 1.2309
    No statistical analyses for this end point

    Secondary: Change From Baseline in Platelet Count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Platelet Count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
    End point description
    Blood samples were collected for measurement of platelet count. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline over time in platelet count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103) was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    17
    Units: 10^9 platelets per liter
    arithmetic mean (standard deviation)
        Change at Week 13 (n=16)
    38.06 ± 35.571
        Change at Week 25 (n=17)
    53.24 ± 46.955
        Change at Week 37 (n=15)
    62.23 ± 46.834
        Change at Week 51 (n=16)
    79.66 ± 89.701
        Change at Week 65 (n=16)
    75.03 ± 52.163
        Change at Week 77 (n=13)
    87.19 ± 70.528
        Change at Week 89 (n=12)
    71.96 ± 60.772
        Change at Week EOS (Week 103) (n=16)
    69.16 ± 53.451
    No statistical analyses for this end point

    Secondary: Change From Baseline in Normalized Liver Volume at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Normalized Liver Volume at Week 51 and EOS (Week 103)
    End point description
    Normalized liver volume was measured by abdominal MRI. Baseline was defined as last data collected prior to the first administration of study drug. Liver volume has been normalized for percent (%) body weight. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg])*100. Change from baseline in normalized liver volume at Week 51 and EOS (Week 103) was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    17
    Units: percent body weight
    arithmetic mean (standard deviation)
        Change at Week 51 (n=17)
    -0.353 ± 0.3485
        Change at Week EOS (Week 103) (n=15)
    -0.447 ± 0.4048
    No statistical analyses for this end point

    Secondary: Change From Baseline in Normalized Spleen Volume at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Normalized Spleen Volume at Week 51 and EOS (Week 103)
    End point description
    Normalized spleen volume was measured by MRI. Spleen volume was normalized for % of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in normalized spleen volume at Week 51 and EOS (Week 103) was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    17
    Units: percent body weight
    arithmetic mean (standard deviation)
        Change at Week 51 (n=17)
    -0.443 ± 0.5987
        Change at Week EOS (Week 103) (n=15)
    -0.556 ± 0.7398
    No statistical analyses for this end point

    Secondary: Change From Baseline in Severity of Bone Pain at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Severity of Bone Pain at Week 51 and EOS (Week 103)
    End point description
    Bone pain was measured by questions taken from the Brief Pain Inventory-short form (BPI-SF). Pain severity was evaluated based on the average of 4 questions from BPI-SF (Questions 3 to 6) assessing worst pain, least pain, average pain, pain right now, each rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) with mild pain-score (0 to 4), moderate pain-score (5 to 6), and severe pain-score (7 to 10). Overall severity score was calculated as average of 4 questions ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A negative change from baseline score indicates improvement. Baseline was defined as last data collected prior to the first administration of study drug. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here,"number of subjects analysed" signifies subjects who were evaluable for this endpoint and “99999” signifies standard deviation was not estimated due to single subject.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    1
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Change at Week 51
    -2.750 ± 99999
        Change at EOS (Week 103)
    -3.250 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Bone Pain Interference Score at Weeks 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Bone Pain Interference Score at Weeks 51 and EOS (Week 103)
    End point description
    Bone pain interference was measured by questions taken from the BPI-SF. Pain interference was evaluated based upon average of 7 questions from BPI-SF (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, each rated on a scale from 0 (does not interfere) to 10 (completely interferes). Overall pain interference score was calculated as average of 7 questions ranging from 0 (does not interfere) to 10 (completely interferes). A negative change from baseline score indicates improvement. Baseline was defined as last data collected prior to the first administration of study drug. ITT analysis population set. Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “99999” signifies standard deviation was not estimated due to single subject.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    1
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Change at Week 51
    -1.286 ± 99999
        Change at Week EOS (Week 103)
    -4.429 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Overall Fatigue Measured by Brief Fatigue Inventory (BFI) at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Change From Baseline in Overall Fatigue Measured by Brief Fatigue Inventory (BFI) at Week 51 and EOS (Week 103)
    End point description
    Overall fatigue was measured by the BFI. BFI was a 9-item questionnaire developed to assess subjective fatigue. Each question asked the respondent to rate the level of their experienced fatigue over the past 24 hours on an 11- point (0-10) scale. First 3 questions-fatigue severity at current, usual, and worst levels, with 0-"no fatigue" and 10-“fatigue”. Next 6 questions-level fatigue interference with daily activities included general activity, mood, walking ability, normal work (both inside and outside the home), relations with other people, and enjoyment of life. A score ranged from 0="no interference" and 10="complete interference. Overall fatigue score was calculated as average score of all 9 items on the BFI ranging from 0="no fatigue" to 10="as bad as you can imagine”. Negative numbers=values lower than mean; positive numbers=values higher than mean. ITT Population. "Number of subjects analysed" signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    5
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Change at Week 51
    -0.111 ± 1.4551
        Change at EOS (Week 103)
    0.044 ± 3.7132
    No statistical analyses for this end point

    Secondary: Number of Subjects With Shift in World Health Organization (WHO) BMD Classifications Based on LS T-Scores at Week 51 and EOS (Week 103)

    Close Top of page
    End point title
    Number of Subjects With Shift in World Health Organization (WHO) BMD Classifications Based on LS T-Scores at Week 51 and EOS (Week 103)
    End point description
    WHO BMD Classifications (Normal Bone Density, Osteopenia, Osteoporosis), bone mineral density was classified based on LS BMD T-scores. BMD T-score was a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale was as follows: -1 and above=normal, -1 to -2.5 = osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis. Number of subjects with shift in WHO BMD classifications based on LS T-Scores at Week 51 and EOS (Week 103) were reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint and “number analysed” signifies subjects who were evaluable at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 51 and EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    10
    Units: Subjects
        Normal Baseline- Normal Week 51 (n=0)
    0
        Normal Baseline- Osteopenia Week 51 (n=0)
    0
        Normal Baseline- Osteoporosis Week 51 (n=0)
    0
        Osteopenia Baseline- Normal Week 51 (n=10)
    1
        Osteopenia Baseline- Osteopenia Week 51 (n=10)
    6
        Osteopenia Baseline- Osteoporosis Week 51 (n=10)
    3
        Osteoporosis Baseline- Normal Week 51(n=6)
    0
        Osteoporosis Baseline- Osteopenia Week 51 (n=6)
    0
        Osteoporosis Baseline- Osteoporosis Week 51 (n=6)
    6
        Normal Baseline- Normal Week 103 (n=1)
    1
        Normal Baseline- Osteopenia Week 103 (n=1)
    0
        Normal Baseline- Osteoporosis Week 103 (n=1)
    0
        Osteopenia Baseline- Normal Week 103 (n=10)
    2
        Osteopenia Baseline- Osteopenia Week 103 (n=10)
    6
        Osteopenia Baseline- Osteoporosis Week 103 (n=10)
    2
        Osteoporosis Baseline- Normal Week 103 (n=5)
    0
        Osteoporosis Baseline- Osteopenia Week 103 (n=5)
    0
        Osteoporosis Baseline- Osteoporosis Week 103 (n=5)
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

    Close Top of page
    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any AE that occurred on or after the time of the first infusion of study drug until 30 days after the last infusion of study drug. Number of subjects with TEAEs were reported. Safety population was defined as all enrolled subjects who received at least one study drug infusion (full or partial).
    End point type
    Secondary
    End point timeframe
    From start of study drug infusion up to follow-up (107 weeks)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    21
    Units: Subjects
    21
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Developed Positive Antivelaglucerase Alfa Antibody Status

    Close Top of page
    End point title
    Number of Subjects Who Developed Positive Antivelaglucerase Alfa Antibody Status
    End point description
    Anti-velaglucerase alfa antibody included antivelaglucerase antibodies (ADA) and neutralizing antivelaglucerase antibodies (NAb). The Anti-velaglucerase antibody status was summarized as categorical variable by positive and negative. Number of subjects who developed positive anti-velaglucerase alfa antibody were reported. Safety population was defined as all enrolled subjects who received at least one study drug infusion (full or partial).
    End point type
    Secondary
    End point timeframe
    Baseline up to EOS (Week 103)
    End point values
    Velaglucerase alfa 60 U/kg
    Number of subjects analysed
    21
    Units: Subjects
    1
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug infusion up to follow-up (107 weeks)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Velaglucerase alfa 60 U/kg
    Reporting group description
    Subjects received 60-minute intravenous (IV) infusion of 60 units per kilogram (U/kg) velaglucerase alfa every other Week (EOW) for 24 months (up to 101 weeks).

    Serious adverse events
    Velaglucerase alfa 60 U/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 21 (9.52%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pyelonephritis
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Velaglucerase alfa 60 U/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 21 (95.24%)
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Asthenia
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Fatigue
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    6
    Injection site bruising
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Pain
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    4
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Blood iron decreased
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Cardiac disorders
    Bundle branch block right
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    11
    Cough
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    3
    Nasal congestion
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Rhinorrhoea
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    11
    Headache
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    15
    Eye disorders
    Eye pain
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    4
    Constipation
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Dyspepsia
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    4
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Urticaria
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    11 / 21 (52.38%)
         occurrences all number
    20
    Myalgia
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    5
    Arthralgia
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    6
    Pain in extremity
         subjects affected / exposed
    8 / 21 (38.10%)
         occurrences all number
    15
    Joint swelling
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Muscle spasms
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    4
    Bone pain
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Musculoskeletal pain
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    4
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Nasopharyngitis
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    6
    Urinary tract infection
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    3
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Sep 2015
    Protocol Amendment 1: -Added details about emergency contact information. -Updated the details in exploratory objectives endpoints. -Added new section about home infusion of VPRIV. -Updated safety language to bring it into alignment with Shire standard language.
    02 Jun 2016
    Protocol Amendment 2: -Added information that all subjects will receive “600 IU 25 hydroxyvitamin D (oral) daily” as concomitant medication. -Changed the evaluation of primary endpoint from 12 months to 24 months. -Changed the evaluation of secondary endpoint from 24 months to 12 months. -Timepoints for measurements of hemoglobin cocentration and platelet count were changed to baseline and weeks 13, 25, 37, 51, 65, 77, 89, and 103 (end of study). -Clarified biomarkers for analysis. -Revised age range to ≥18 and ≤65 years of age. -Updated emergency contact information. -Added specific guidance for contraception.
    06 Jul 2016
    Protocol Amendment 3: -The minimum age for inclusion had been changed to 18 years; therefore, informed consent by parents was eliminated. -Added “HBsAg, HCV, HIV, and 25 hydroxyvitamin D blood test” as a safety laboratory tests to be performed at screening. -Changed the assessment of primary efficacy endpoint at the baseline visit to occur at the screening visit instead.
    04 May 2017
    Protocol Amendment 4: -The dose of Vitamin D was revised from 600 IU to 800 IU. -The subject age range for the enrollment in the study was increased from ≥18 and ≤65 to ≥18 and ≤70 years. -The definition of IRR was updated to match the definition in summary of product characteristics. -The assessments of BMB and LS BMD Z score were eliminated at Week 25 and Week 77 to ease subject burden as data from these visits will not be used in the determination of any endpoints. -Added criterion of BMD T-score to facilitate enrollment after consideration of this measure as an appropriate alternative to BMD Z-score. -Deleted “Change in the quadriceps cross sectional area and measures of relevance to determine lean muscle mass are additional exploratory endpoints.” as the proper imaging modality for its measurement was not being performed and MRI was no longer considered to be an adequate measure. -The window of study procedures was changed to ±7 days to allow for subject rescheduling and to facilitate protocol execution.--
    26 Jul 2018
    Protocol Amendment 5: -The number of subjects planned for enrollment was reduced from approximately 40 subjects to at least 19 subjects. -The number of expected evaluable subjects was decreased from 34 subjects to 13 subjects. -The key secondary objectives were re-classified as secondary objectives. -The BMB scoring was changed to follow the DeMayo et al. method instead of the Maas et al. method. -The power provided by the sample size for the detection of change in the primary endpoint was changed from 99% to 90%. -The early subject discontinuation rate previously estimated at 15% was revised to 30%. -Viral testing was removed from the list of screening visit assessments.
    02 Oct 2020
    Protocol Amendment 6: - Two new objectives and endpoints were added. Objective: * BMD as measured by the change from baseline in g/cm2 after 12 months of treatment. * BMD as measured by the change from baseline in g/cm2 after 24 months of treatment. Endpoints: * Change from baseline to 12 months (Week 51) in BMD reported as g/cm2. Assessments will be performed at the screening visit and Weeks 51. * Change from baseline to 24 months (Week 103 [end of study]) in BMD reported as g/cm2. Assessments will be performed at the screening visit and Week 103 (end of study) - The Brief Pain Inventory – Short Form was updated to “Questions taken from the BPI-SF©” - Added the optional transfer of study visit weeks 77 and/or 89 to home therapy and the addition of dose continuation infusions due to the COVID-19 pandemic. - Added that infusion of VPRIV may be delivered intravenously with an in-line sterilizing filter that has a rated pore size of 0.22 micrometer (mcm).

    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
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA