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    Clinical Trial Results:
    A Long-Term, Open-Label, Multicenter, Phase IV Study to Assess Longitudinal Changes on Height and Weight in Patients with MPS II Who Are Receiving Elaprase and Started Treatment with Elaprase at < 6 Years of Age

    Summary
    EudraCT number
    		 2014-004804-31
    Trial protocol
    		 DE  
    Global end of trial date
    29 Jul 2025

    Results information
    Results version number
    		 v2(current)
    This version publication date
    24 May 2026
    First version publication date
    13 Feb 2026
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    information updated

    Trial information

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    Trial identification
    Sponsor protocol code
    SHP-ELA-401
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02455622
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, MA, United States, 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Jul 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jul 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of this study was to assess longitudinal changes in the following parameters in patients with MPS II who began Elaprase treatment at <6 years of age and who are receiving treatment with Elaprase: • height • weight
    Protection of trial subjects
    Each participant or their legally authorized representative signed an informed consent form (ICF) before participating in the study
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Oct 2015
    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
    Brazil: 1
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Czechia: 3
    Country: Number of subjects enrolled
    Dominican Republic: 1
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Thailand: 2
    Country: Number of subjects enrolled
    Malaysia: 2
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Serbia: 1
    Country: Number of subjects enrolled
    Philippines: 2
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Viet Nam: 10
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    United States: 6
    Worldwide total number of subjects
    66
    EEA total number of subjects
    16
    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)
    19
    Children (2-11 years)
    47
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at various investigative sites globally from 28 October 2015 to 29 July 2025.

    Pre-assignment
    Screening details
    		 Treatment-naïve participants with mucopolysaccharidosis II(MPS II) were enrolled to receive weekly intravenous(IV) infusions of Elaprase starting at less than(<)6 years of age. Data for primary growth analyses was utilized from the Hunter Outcome Survey (HOS) registry participants for 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
    Are arms mutually exclusive
    Yes

    Arm title
    		 Prospective Set
    Arm description
    		 Participants received once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and were followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elaprase
    Investigational medicinal product code
    Other name
    Idursulfase
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Weekly Elaprase infusion from Week 1 till minimum of 5 years or until they reach their 10th birthday, whichever is longer.

    Arm title
    		 Hunter Outcome Survey (HOS) Treated Set
    Arm description
    		 Participants in the HOS patient registry, who were treated, were combined with the Prospective Set in the Primary Growth Analysis for this study using their height and weight data.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 HOS Untreated Set
    Arm description
    		 Participants in the HOS patient registry, who were not treated, were used as the comparator in the Primary Growth Analysis for this study using their height and weight data.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Prospective Set Hunter Outcome Survey (HOS) Treated Set HOS Untreated Set
    Started
    21
    19
    26
    Completed
    17
    19
    26
    Not completed
    4
    0
    0
         Adverse event, serious fatal
    1
    -
    -
         Reason Not Specified
    1
    -
    -
         Non-compliance with study drug
    2
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Prospective Set
    Reporting group description
    		 Participants received once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and were followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.

    Reporting group title
    Hunter Outcome Survey (HOS) Treated Set
    Reporting group description
    		 Participants in the HOS patient registry, who were treated, were combined with the Prospective Set in the Primary Growth Analysis for this study using their height and weight data.

    Reporting group title
    HOS Untreated Set
    Reporting group description
    		 Participants in the HOS patient registry, who were not treated, were used as the comparator in the Primary Growth Analysis for this study using their height and weight data.

    Reporting group values
    		 Prospective Set Hunter Outcome Survey (HOS) Treated Set HOS Untreated Set Total
    Number of subjects
    		 21 19 26 66
    Age Categorical
    Units: Subjects
        Less than (<)2 years
    		 2 2 15 19
        Greater than equal to (>=) 2 years
    		 19 17 11 47
    Gender categorical
    Units: Subjects
        Female
    		 0 0 0 0
        Male
    		 21 19 26 66
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 15 1 1 17
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 0 1 2 3
        White
    		 4 14 23 41
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 2 3 0 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 0 0 2
        Not Hispanic or Latino
    		 9 0 0 9
        Unknown or Not Reported
    		 10 19 26 55

    End points

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    End points reporting groups
    Reporting group title
    Prospective Set
    Reporting group description
    		 Participants received once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and were followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.

    Reporting group title
    Hunter Outcome Survey (HOS) Treated Set
    Reporting group description
    		 Participants in the HOS patient registry, who were treated, were combined with the Prospective Set in the Primary Growth Analysis for this study using their height and weight data.

    Reporting group title
    HOS Untreated Set
    Reporting group description
    		 Participants in the HOS patient registry, who were not treated, were used as the comparator in the Primary Growth Analysis for this study using their height and weight data.

    Subject analysis set title
    Combined Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Combined Set included data from all participants in both the Efficacy Set and the HOS Treated Set. Efficacy Set includes participants who received once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and were followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.

    Primary: Height Overall

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    End point title
    		 Height Overall [1]
    End point description
    The effect of treatment on growth evaluated in terms of height. As pre-specified in the statistical analysis plan (SAP), descriptive analysis for this outcome measure was planned for the Combined Set and HOS Untreated Set arms and the assessment for Primary Growth Analysis was considered for the Combined Set in comparison to the HOS Untreated Set. The Combined Set included treated participants enrolled in this study (prospective participants) as well as treated participants from the HOS registry. The Combined Set included data from all participants in both the Efficacy Set and the HOS Treated Set. The Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. The HOS Treated Set included all participants enrolled in the HOS registry that met the criteria. The HOS Untreated Set included untreated participants from the HOS registry that met the criteria.
    End point type
    Primary
    End point timeframe
    Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [1] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 HOS Untreated Set Combined Set
    Number of subjects analysed
    26
    40
    Units: centimeter (cm)
        least squares mean (standard error)
    108.143 ( 1.7668 )
    113.759 ( 1.211 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    HOS Untreated Set v Combined Set
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 Linear mixed model
    Parameter type
    		 LS Mean Difference
    Point estimate
    5.616
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.329
         upper limit
    		 9.903
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.1497

    Primary: Weight Overall

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    End point title
    		 Weight Overall [2]
    End point description
    The effect of treatment on growth was evaluated, in terms of weight. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned for the Combined Set and HOS Untreated Set arms and the assessment for Primary Growth Analysis was considered for the Combined Set in comparison to the HOS Untreated Set. The Combined Set included treated participants enrolled in this study (prospective participants) as well as treated participants from the HOS registry. The Combined Set included data from all participants in both the Efficacy Set and the HOS Treated Set. The Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. The HOS Treated Patients included all participants enrolled in the HOS registry that met the criteria. The HOS Untreated Set included untreated participants from the HOS registry that met the criteria.
    End point type
    Primary
    End point timeframe
    Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 HOS Untreated Set Combined Set
    Number of subjects analysed
    26
    40
    Units: kilograms (kg)
        least squares mean (standard error)
    26.11 ( 1.1647 )
    25.164 ( 0.8382 )
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    HOS Untreated Set v Combined Set
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5106
    Method
    		 Linear mixed model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.946
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.8
         upper limit
    		 1.908
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.4308

    Primary: Change from Baseline in Height Measured by Z- score

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    End point title
    		 Change from Baseline in Height Measured by Z- score [3] [4]
    End point description
    Z-score(standard score) for height was calculated as number of standard deviations(SD) by which mean height(MH) of each arm was above/below MH of reference population. Z-scores were calculated based on World Health Organization Drug Dictionary(WHO-DD) growth charts(for age less or equal to[≤] 24 months(m))& Centers for Disease Control & Prevention(CDC) growth charts(for age more than[>]24 m)normal height-for-age data. Normal growth Z-score range:-1 to +1.Z-score:0 represents reference mean & 50th percentile. Z-score of more than or equal to(≥)+2=above normal range & taller than average (avg.) & Z-score ≤-2=shorter stature than avg. & may indicate growth issues. Score is calculated as Z=(Actual value for participant in study-Mean value of healthy population(HP))/(SD of HP). Combined & HOS Untreated Set was utilized. Subjects analysed=number of participants with data available for analysis for this end point.
    End point type
    Primary
    End point timeframe
    Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [3] - 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 statistics is provided for this end point.
    [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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 HOS Untreated Set Combined Set
    Number of subjects analysed
    22
    39
    Units: height z score
        arithmetic mean (standard deviation)
    -4.228 ( 1.4616 )
    -1.135 ( 1.3480 )
    No statistical analyses for this end point

    Primary: Change from Baseline in Weight Measured by Z-score

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    End point title
    		 Change from Baseline in Weight Measured by Z-score [5] [6]
    End point description
    Z-score (standard score) for weight was calculated as number of SDs by which mean weight (MW) of each arm was above or below the MW of the reference population. Z-scores were calculated based on WHO-DD growth charts (for age ≤ 24 m) & CDC growth charts (for age > 24 m) normal weight-for-age data. Normal range for growth Z score is defined as -1 to +1. Z-score: 0 represents reference population mean & 50th percentile. Positive Z-score of ≥ +2= above avg. weight (overweight). Negative Z-score of ≤ -2= below avg. weight (underweight). Score is calculated as Z=(Actual value for participant in study-Mean value of HP)/ (SD of HP). As per SAP, descriptive analysis was planned for Combined & HOS Untreated Set arms, with Primary Growth Analysis assessed for Combined Set compared to HOS Untreated Set. Combined and HOS untreated set was utilized. Subjects analysed is the number of participants with data available for analysis for this outcome measure.
    End point type
    Primary
    End point timeframe
    Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [5] - 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 statistics is provided for this end point.
    [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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 HOS Untreated Set Combined Set
    Number of subjects analysed
    26
    39
    Units: weight z score
        arithmetic mean (standard deviation)
    -2.337 ( 1.9014 )
    -1.161 ( 1.3259 )
    No statistical analyses for this end point

    Primary: Number of Participants With Clinical Significant Abnormal Neurological Examination

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    End point title
    		 Number of Participants With Clinical Significant Abnormal Neurological Examination [7] [8]
    End point description
    A full physical examination will be performed with a thorough review of body systems. Physical examinations will include a review of the patient’s general appearance, neurological examination, as well as evaluation of the body systems. Any abnormal change in findings will be recorded as an adverse event (AE). The Safety Analysis Set consisted of all prospective participants who received any amount of investigational product (IP). As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all treated participants in this study.
    End point type
    Primary
    End point timeframe
    From Screening to End-of-Study (approximately 9.75 years)
    Notes
    [7] - 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 statistics is provided for this end point.
    [8] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Clinically Significant Abnormal Urinalysis Values

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    End point title
    		 Number of Participants With Clinically Significant Abnormal Urinalysis Values [9] [10]
    End point description
    Reported here is the number of participants with clinically significant abnormal values in urinalysis tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value. The Safety Analysis Set consisted of all prospective participants who received any amount of IP. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all treated participants in this study.
    End point type
    Primary
    End point timeframe
    From screening to End-of-Study (approximately 9.75 years)
    Notes
    [9] - 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 statistics is provided for this end point.
    [10] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
        Bacteria (/High-power field (HPF))
    5
        Erythrocytes (/HPF)
    1
        Glucose (milligrams per deciliter (mg/dl))
    1
        Leukocyte Esterase
    1
        Mucous Threads
    1
        Nitrite
    4
        Occult Blood
    1
        Protein (mg/dL)
    3
        Specimen Appearance
    6
        Squamous Epithelial Cells (/HPF)
    2
        Squamous Transitional Epithelial Cells (/HPF)
    1
        Triple Phosphate Crystals (/HPF)
    2
        Yeast Cells
    1
        pH (pH)
    3
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAE)

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAE) [11] [12]
    End point description
    An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered product-related. This includes an exacerbation of a pre-existing condition. A TEAE is defined as an AE with an onset that occurs after receiving study drug. The Safety Analysis Set consisted of all prospective participants who received any amount of IP. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all treated participants in this study.
    End point type
    Primary
    End point timeframe
    From screening to End-of-Study (approximately 9.75 years)
    Notes
    [11] - 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 statistics is provided for this end point.
    [12] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
    21
    No statistical analyses for this end point

    Primary: Number of Participants With Clinically Significant Abnormal Serum Chemistry Values

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    End point title
    		 Number of Participants With Clinically Significant Abnormal Serum Chemistry Values [13] [14]
    End point description
    Reported here is the number of participants with clinically significant abnormal values in serum chemistry tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value. The Safety Analysis Set consisted of all prospective participants who received any amount of IP. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all treated participants in this study.
    End point type
    Primary
    End point timeframe
    From screening to End-of-Study (approximately 9.75 years)
    Notes
    [13] - 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 statistics is provided for this end point.
    [14] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
        Alanine Aminotransferase (units per liter (U/L))
    1
        Aspartate Aminotransferase (U/L)
    1
        Gamma Glutamyl Transferase (U/L)
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Clinically Significant Abnormal Hematology Values

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    End point title
    		 Number of Participants With Clinically Significant Abnormal Hematology Values [15] [16]
    End point description
    Reported here is the number of participants with clinically significant abnormal values in haematological tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value. The Safety Analysis Set consisted of all prospective participants who received any amount of IP. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all treated participants in this study.
    End point type
    Primary
    End point timeframe
    Screening to End-of-Study (approximately 9.75 years)
    Notes
    [15] - 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 statistics is provided for this end point.
    [16] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
        Ery. Mean Corpuscular Hemoglobin (picogram (pg))
    1
        Ery. Mean Corpuscular Volume (femtoliter (fL))
    1
        Hemoglobin (gram per litre (g/L))
    1
    No statistical analyses for this end point

    Secondary: Observed Value of Height Velocity From Baseline to End of Study

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    End point title
    		 Observed Value of Height Velocity From Baseline to End of Study [17]
    End point description
    Height velocity was calculated as the difference in height, divided by the difference in age between consecutive study visits. BL denotes Baseline, HV denotes Height Velocity, EOS denotes End-of-Study and Y denotes Years for the reported categories. Efficacy Set: all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. Combined Set included data from all participants in both Efficacy Set and HOS Treated Set. HOS Treated Set included all participants enrolled in HOS registry that meet the criteria. HOS Untreated Set included untreated participants from HOS registry that meet the criteria. Number analysed (n) is the number of participants with data available for the specified categories.
    End point type
    Secondary
    End point timeframe
    Prospective participants: From Baseline till End-of-Study Treatment (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [17] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set HOS Untreated Set Combined Set
    Number of subjects analysed
    21
    26
    40
    Units: centimeters (cm)/year
    arithmetic mean (standard deviation)
        Overall HV:BL to <6Y of Age (n=16,22,32)
    5.401 ( 2.5815 )
    6.557 ( 2.5902 )
    6.556 ( 2.6803 )
        Overall HV:6Y of Age to EOS (n=20,18,38)
    2.699 ( 1.7610 )
    1.761 ( 1.2178 )
    3.571 ( 1.8064 )
    No statistical analyses for this end point

    Secondary: Observed Value of Weight Velocity From Baseline to End of Study

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    End point title
    		 Observed Value of Weight Velocity From Baseline to End of Study [18]
    End point description
    Weight velocity was be calculated as the difference in weight, divided by the difference in age between consecutive study visits. Efficacy Set: all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. Combined Set included data from all participants in both Efficacy Set and HOS Treated Set. HOS Treated Set included all participants enrolled in HOS registry that meet the criteria. HOS Untreated Set included untreated participants from HOS registry that meet criteria. BL denotes baseline, Y denotes Years and V denotes Velocity for the reported categories. Number analyzed (n) is the number of participants with data available for the specified categories.
    End point type
    Secondary
    End point timeframe
    Prospective participants: From Baseline till End-of-Study Treatment (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22
    Notes
    [18] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set HOS Untreated Set Combined Set
    Number of subjects analysed
    21
    26
    40
    Units: kilograms (kg)/year
    arithmetic mean (standard deviation)
        Overall V:BL to <6Y of Age (n=16,22,32)
    1.772 ( 1.2029 )
    3.670 ( 2.0005 )
    2.475 ( 1.4550 )
        Overall V: 6Y of Age to EOS (n=20,19,38)
    1.573 ( 1.3198 )
    1.445 ( 0.8324 )
    2.305 ( 1.7134 )
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline for Urinary glycosaminoglycans (uGAG) Levels Normalized to Urine Creatinine 

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    End point title
    		 Percent Change From Baseline for Urinary glycosaminoglycans (uGAG) Levels Normalized to Urine Creatinine  [19]
    End point description
    Urinary GAG levels were normalized to urine creatinine (normalized uGAG) and reported as mg uGAG/ millimoles (mmol) creatinine. The Efficacy Set is defined as all prospective participants who had a baseline and at least 1 post-baseline efficacy assessment. Subjects analysed is the number of participants with data available for analysis for this outcome measure at the end-of-study. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set in this study.
    End point type
    Secondary
    End point timeframe
    Baseline to End-of-Study (Approximately 9.75 years)
    Notes
    [19] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    20
    Units: percent change
    arithmetic mean (standard deviation)
        Normalized uGAG (mg/mmol)
    -70.446 ( 17.8741 )
    No statistical analyses for this end point

    Secondary: Normalized uGAG Divided by Upper Llimit of Normal for Age (uGAG/ULN) Every 12 Months

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    End point title
    		 Normalized uGAG Divided by Upper Llimit of Normal for Age (uGAG/ULN) Every 12 Months [20]
    End point description
    Normalized uGAG was divided by the upper limit of normal for age (uGAG/ULN), where the ULN for uGAG was obtained from Mayo Clinic. The Efficacy Set is defined as all prospective participants who had a baseline and at least 1 post-baseline efficacy assessment. Number analyzed (n) is the number of participants with data available for analysis for this outcome measure at the end-of-study. 9999 denotes Standard Deviation (SD) was not estimable for a single participant. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set in this study.
    End point type
    Secondary
    End point timeframe
    Baseline to End-of-Study (Approximately 9.75 years)
    Notes
    [20] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: Normalized uGAG/ULN
    arithmetic mean (standard deviation)
        Normalized uGAG/ULN: Baseline(n=20)
    5.052 ( 1.0376 )
        Normalized uGAG/ULN: 12 Months(n=20)
    2.315 ( 0.7655 )
        Normalized uGAG/ULN: 24 Months(n=19)
    2.096 ( 0.7657 )
        Normalized uGAG/ULN: 36 Months(n=17)
    2.182 ( 0.9339 )
        Normalized uGAG/ULN: 48 Months(n=17)
    2.063 ( 0.6853 )
        Normalized uGAG/ULN: 60 Months(n=7)
    2.197 ( 0.8870 )
        Normalized uGAG/ULN: 72 Months(n=3)
    2.190 ( 1.0945 )
        Normalized uGAG/ULN: 84 Months(n=1)
    0.830 ( 9999 )
        Normalized uGAG/ULN: End of Study(n=21)
    2.055 ( 1.1866 )
    No statistical analyses for this end point

    Secondary: Spleen Volume

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    End point title
    		 Spleen Volume [21]
    End point description
    Spleen volume was assessed using abdominal ultrasonography. Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. Subjects analysed is the number of participants with data available for analysis. Number analyzed (n) is the number of participants with data available for analysis at the specified time points. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set.
    End point type
    Secondary
    End point timeframe
    Baseline up to 24 Months
    Notes
    [21] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    20
    Units: mL
    arithmetic mean (standard deviation)
        Spleen Volume: Baseline (n=8)
    104.593 ( 29.9658 )
        Spleen Volume: 24 Months (n=14)
    98.427 ( 47.8022 )
    No statistical analyses for this end point

    Secondary: Liver Volume

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    End point title
    		 Liver Volume [22]
    End point description
    Liver volume was assessed using abdominal ultrasonography. Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. Subjects analysed is the number of participants with data available for analysis. Number analyzed (n) is the number of participants with data available for analysis at the specified time points. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set.
    End point type
    Secondary
    End point timeframe
    Baseline up to 24 Months
    Notes
    [22] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    20
    Units: milliliters (mL)
    arithmetic mean (standard deviation)
        Liver Volume: Baseline (n=8)
    105.855 ( 16.8925 )
        Liver Volume: 24 Months (n=14)
    87.811 ( 7.0147 )
    No statistical analyses for this end point

    Secondary: Joint Mobility, as Measured by Joint Range of Motion (JROM) Scores, Including Upper-Limb and Lower-Limb Joint Scores

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    End point title
    		 Joint Mobility, as Measured by Joint Range of Motion (JROM) Scores, Including Upper-Limb and Lower-Limb Joint Scores [23]
    End point description
    Global JROM(% normal range of motion [ROM]) = average (avg.) of 11 ratios multiplied by 100. Ratios are Left/Right means of passive ROM in Shoulder(Flexion [flex]/Extension [ext],Abduction,Internal/External Rotation (I/ER)),Elbow (flex/ext),Wrist (flex/ext),Index Finger(flex/ext [Combined Metacarpophalangeal joint, Proximal interphalangeal joint, Distal interphalangeal joint motion]),Hip(flex/ext,Abduction, I/ER),Knee(flex/ext) & Ankle(Dorsiflexion)divided by normal range(reference: American Academy of Orthopedic Surgeons & American Medical Association).For reported values of upper limb(UL) & lower limb(LL) scores,UL score=avg. of 3 joint scores in UL(shoulder-elbow-wrist) & LL score=avg. of 3 joint scores in LL(hip-knee-ankle).JM(in degrees) was avg. across both sides,divided by normal value & multiplied by 100 to yield a % score. Score >100% occurs when measured JM exceeds normal reference values. Subjects analysed=participants with data available for analysis for this end point at
    End point type
    Secondary
    End point timeframe
    From Baseline to End-of-Study (approximately 9.75 years)
    Notes
    [23] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    20
    Units: score on a scale
    arithmetic mean (standard deviation)
        Lower Limb
    94.50 ( 31.634 )
        Upper Limb
    104.24 ( 21.471 )
    No statistical analyses for this end point

    Secondary: Distance Walked, as Measured by Six Minute Walk Test (6MWT)

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    End point title
    		 Distance Walked, as Measured by Six Minute Walk Test (6MWT) [24]
    End point description
    The 6MWT was conducted according to the American Thoracic Society guidelines for the 6MWT in participants who were able to walk. The distance achieved in meters was recorded. Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set in this study.
    End point type
    Secondary
    End point timeframe
    From Baseline to End-of-Study (approximately 9.75 years)
    Notes
    [24] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: meters
    arithmetic mean (standard deviation)
        End of Study
    224.2 ( 178.42 )
    No statistical analyses for this end point

    Secondary: Quality of Life, as Measured by Hunter-Syndrome Functional Outcome in Clinical Understanding Scale (HS-FOCUS) 

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    End point title
    		 Quality of Life, as Measured by Hunter-Syndrome Functional Outcome in Clinical Understanding Scale (HS-FOCUS)  [25]
    End point description
    The participant's QoL was assessed using the HS-FOCUS (shortened version) questionnaire. The HS-FOCUS (shortened version) questionnaire has 5 function domains (walking/standing, grip/reach, schooling/work, activities, and breathing). The scale of the 5 function domains ranges from 0 to 3, with a 3-score denoting highest disability: 0: with no difficulty;1: with some difficulty; 2: with much difficulty; 3: unable to do; Missing: Does not apply. The response option "Does not apply" is treated as "missing" with no score, the same as if the item had not been completed in the questionnaire. Higher scores indicate worse functional outcomes/greater disability. Efficacy Set was utilized.n=number of participants with data available for the specified categories.As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set in this study.
    End point type
    Secondary
    End point timeframe
    Baseline to End-of-Study (Approximately 9.75 years)
    Notes
    [25] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: score on a scale
    arithmetic mean (standard deviation)
        End of Study: Walking/Standing (n=21)
    1.19 ( 1.042 )
        End of Study: Grip/Reach (n=21)
    1.83 ( 0.986 )
        End of Study: School/Work (n=17)
    1.97 ( 1.166 )
        End of Study: Activities (n=20)
    1.68 ( 1.238 )
        End of Study: Breathing (n=21)
    1.00 ( 0.929 )
    No statistical analyses for this end point

    Secondary: Impact of Illness on Ability to Function in Daily Life, as Measured by Childhood Health Assessment Questionnaire (CHAQ Parent Report)

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    End point title
    		 Impact of Illness on Ability to Function in Daily Life, as Measured by Childhood Health Assessment Questionnaire (CHAQ Parent Report) [26]
    End point description
    Impact on ability to function in daily life was measured by the CHAQ (Parent Report).CHAQ includes 30 items measured on a scale of 0-3: 0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=Unable to do; Missing: Does not apply. It evaluates functional abilities across 8 domains (dressing, hygiene, arising, eating, walking, reach, grip & activities). Result=Disability Index. Highest scoring item in each category determines the score for that category with higher scores= worse functioning/higher disability. Discomfort Index & Health Status Index are measured on separate 15 cm scales. Distance from the left end of the scale to the respondent's mark is measured and multiplied by 0.2 to calculate the score (range 0-3). Discomfort & Health Status Index scores were rescaled to 0-100 scales. Higher scores= greater discomfort/worse health status. Efficacy Set was utilized.
    End point type
    Secondary
    End point timeframe
    Baseline to End-of-Study (approximately 9.75 years)
    Notes
    [26] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: score on a scale
    arithmetic mean (standard deviation)
        Disability Index
    2.143 ( 0.7334 )
        Discomfort Index
    16.4 ( 25.57 )
        Health Status Index
    51.9 ( 33.12 )
    No statistical analyses for this end point

    Secondary: Adaptive Behavior, as Measured by the Vineland Adaptive Behavior Scales (VABS II)

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    End point title
    		 Adaptive Behavior, as Measured by the Vineland Adaptive Behavior Scales (VABS II) [27]
    End point description
    Adaptive behavior was assessed using parent/caregiver report on VABS-II, a standardized norm-referenced tool to evaluate adaptive behavior for ages 0-90. VABS-II has 1 composite score(Adaptive Behavior Composite [ABC]),reflecting overall adaptive ability. ABC comprises 4 domain scores(DS) in participants <7years old(Communication(CM),Daily Living Skills(DLS),Socialization(SC),&Motor Skills(MS))& 3 DS in participants ≥7years of age(CM,DLS,&SC).ABC standard score(SS) is derived from domain SS per VABS-II manual(not a simple sum/avg. of reported SS).DS are SS derived from combination of 11 subdomain scores according to VABS-II scoring rules/manual. Scale for ABC & domain SS ranges between 20 & 160.ABC & DS have a normative mean=100, with SD=15 & subdomain scores are normed with a mean=15 & SD=3.Higher scores=better, while lower scores=worse adaptive functioning. Efficacy Set was utilized. Subjects analysed=participants with data available for analysis for this outcome measure at the EOS.
    End point type
    Secondary
    End point timeframe
    Baseline to End-of-Study (approximately 9.75 years)
    Notes
    [27] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    16
    Units: score on a scale
    arithmetic mean (standard deviation)
        EOS:Adaptive Behavior Composite Standard Score
    48.1 ( 19.07 )
        EOS:Communication Domain Standard Score
    44.4 ( 15.19 )
        EOS:Daily Living Domain Standard Score
    51.6 ( 22.53 )
        EOS:Motor Skills Domain Standard Score
    28.5 ( 13.22 )
        EOS: Social Domain Standard Score
    53.6 ( 19.88 )
    No statistical analyses for this end point

    Secondary: Anti-Idursulfase Antibodies (ADA) in Serum

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    End point title
    		 Anti-Idursulfase Antibodies (ADA) in Serum [28]
    End point description
    Blood samples were collected and analyzed for determination of anti-idursulfase antibodies every 6 months in SHP-ELA-401. Analysis of anti-idursulfase antibodies including neutralizing antibodies (NAb) was conducted using validated 3-tier immunoassay methods (screening, confirmatory, and titer). Efficacy Set consisted of all prospective participants, who had a baseline and at least 1 post-baseline efficacy assessment. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned only for the reported arm, which included all prospective participants in the Efficacy Set in this study.
    End point type
    Secondary
    End point timeframe
    From Baseline to End-of-Study (Approximately 9.75 years)
    Notes
    [28] - 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: Descriptive analysis for this end point was planned only for the arm groups where it is reported.
    End point values
    		 Prospective Set
    Number of subjects analysed
    21
    Units: participants
        ADA Positive (ADA+)
    21
        NAb Positive (NAb+)
    15
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline until the end of study (up to approximately 9.75 years)
    Adverse event reporting additional description
    The Safety Analysis Set consisted of all prospective participants who received any amount of IP. Adverse Event data only for participants receiving study drug in this study was collected.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Prospective Set
    Reporting group description
    		 Participants received once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and were followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.

    Serious adverse events
    		 Prospective Set
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 21 (52.38%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Sudden death
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Chills
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Papilloedema
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Obstructive airways disorder
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Systemic lupus erythematosus
         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
    Sepsis
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypernatraemia
         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
    		 Prospective Set
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 21 (100.00%)
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    4
    Procedural pain
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    4
    Head injury
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Ear injury
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Thermal burn
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Skin laceration
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Cardiac disorders
    Aortic valve incompetence
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    5
    Mitral valve incompetence
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    5
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Seizure
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    11 / 21 (52.38%)
         occurrences all number
    48
    Gait disturbance
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Eye disorders
    Blepharitis
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Diarrhoea
         subjects affected / exposed
    13 / 21 (61.90%)
         occurrences all number
    21
    Constipation
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Anal fissure
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Respiratory, thoracic and mediastinal disorders
    Wheezing
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Rhinitis allergic
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    4
    Oropharyngeal pain
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    5
    Cough
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    11
    Rhinorrhoea
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    227
    Dermatitis
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    3
    Dermatitis allergic
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    4
    Dermatitis atopic
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Dermatitis diaper
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Eczema
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    3
    Erythema
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Rash
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Rash macular
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    4
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Infections and infestations
    Carbuncle
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Conjunctivitis
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    8
    Ear infection
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    3
    Furuncle
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    4
    Gastroenteritis
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    8
    COVID-19
         subjects affected / exposed
    7 / 21 (33.33%)
         occurrences all number
    8
    Bronchitis
         subjects affected / exposed
    11 / 21 (52.38%)
         occurrences all number
    24
    Otitis media
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    7
    Nasopharyngitis
         subjects affected / exposed
    14 / 21 (66.67%)
         occurrences all number
    96
    Influenza
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Impetigo
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Viral infection
         subjects affected / exposed
    7 / 21 (33.33%)
         occurrences all number
    11
    Varicella
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    4
    Urinary tract infection
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    6
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 21 (61.90%)
         occurrences all number
    38
    Tonsillitis
         subjects affected / exposed
    5 / 21 (23.81%)
         occurrences all number
    5
    Sinusitis
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    5
    Rhinitis
         subjects affected / exposed
    7 / 21 (33.33%)
         occurrences all number
    16
    Pneumonia
         subjects affected / exposed
    4 / 21 (19.05%)
         occurrences all number
    5
    Pharyngotonsillitis
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Pharyngitis
         subjects affected / exposed
    6 / 21 (28.57%)
         occurrences all number
    8
    Parotitis
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2
    Otitis media acute
         subjects affected / exposed
    3 / 21 (14.29%)
         occurrences all number
    3
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    2 / 21 (9.52%)
         occurrences all number
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Nov 2015
    The following changes were made as per Amendment 01: 1) Added section regarding benefit/risk assessment of participants treated with Elaprase in completed clinical studies. 2) Added a section regarding monitoring of burden/risk to participants in this study (SHP-ELA-401). 3) Added a Visit window of 48 hours for completion of study activities for all visits. 4) Added Exclusion criterion regarding hypersensitivity to active substance or excipients for Group 1: Prospective Patient Group. 5) Allowed home infusion of Elaprase by a trained healthcare provider, with Sponsor approval.
    05 Aug 2016
    The following changes were made as per Amendment 02: 1) Changed planned enrollment and Primary Growth Analysis. 2) Added CRIM status evaluation and interpretation. 3) Changed study objectives. 4) Changed study outcome measures. 5) Added visit to the study schedule of events.

    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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