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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44238   clinical trials with a EudraCT protocol, of which   7338   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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 Extension of Study HGT-HIT-094 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Idursulfase Administered in Conjunction with ELAPRASE® in Patients with Hunter Syndrome and Cognitive Impairment

    Summary
    EudraCT number
    		 2014-004143-13
    Trial protocol
    		 GB   ES   FR  
    Global end of trial date
    18 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Nov 2024
    First version publication date
    02 Nov 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SHP609-302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02412787
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Shire Human Genetic Therapies, Inc.
    Sponsor organisation address
    300 Shire Way, Lexington, Massachusetts, United States, 02421
    Public contact
    Study Director, Takeda, N/A N/A, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, N/A N/A, 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
    18 Apr 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study was to evaluate the long-term safety of intrathecal (IT) idursulfase-IT along with standard-of-care therapy with elaprase in participants with Hunter Syndrome who completed Study HGT-HIT-094 (NCT02055118).
    Protection of trial subjects
    Each participant signed an informed consent form (ICF) before participating in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 35
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Mexico: 4
    Worldwide total number of subjects
    56
    EEA total number of subjects
    9
    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)
    1
    Children (2-11 years)
    54
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants took part in the study at 22 investigative sites in Australia, Canada, France, Mexico, Spain, the United Kingdom, and the United States of America (USA) from 14 April 2015 to 18 April 2024.

    Pre-assignment
    Screening details
    		 A total of 56 participants with a diagnosis of Hunter Syndrome who completed the Study HGT-HIT-094 (NCT02055118) received idursulfase-IT in conjunction with elaprase therapy.

    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
    		 Idursulfase-IT
    Arm description
    		 Participants received 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with elaprase for 480 weeks. Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (>8 months to 30 months of age) or 10 mg (>30 months to 3 years of age) of idursulfase-IT.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elaprase
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Elaprase as standard-of-care for 480 weeks.

    Investigational medicinal product name
    Idursulfase-IT
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    Idursulfase-IT once every 28 days for 480 weeks.

    Number of subjects in period 1
    		Idursulfase-IT
    Started
    56
    Completed
    23
    Not completed
    33
         Termination by Sponsor
    21
         Termination by Investigator
    1
         Technical Problems
    1
         Withdrawal by Subject
    9
         Reason not Specified
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Idursulfase-IT
    Reporting group description
    		 Participants received 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with elaprase for 480 weeks. Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (>8 months to 30 months of age) or 10 mg (>30 months to 3 years of age) of idursulfase-IT.

    Reporting group values
    		 Idursulfase-IT Total
    Number of subjects
    		 56
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 4.89 ( 2.117 ) -
    Gender categorical
    Units: Subjects
        Male
    		 56 56
        Female
    		 0 0
    Race
    Units: Subjects
        Asian
    		 4 4
        Black or African American
    		 1 1
        White
    		 41 41
        Other
    		 10 10
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 14 14
        Not Hispanic or Latino
    		 38 38
        Not Reported
    		 4 4
    Subject analysis sets

    Subject analysis set title
    Idursulfase-IT 10 mg, Delayed IT
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Delayed IT group included participants who were randomised to the no IT treatment cohort in Study HGT-HIT-094 and began IT treatment in Study SHP609-302.

    Subject analysis set title
    Idursulfase-IT 10 mg, Early IT
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Early IT group included participants who were randomised to the IT treatment cohort in Study HGT-HIT-094 and continued in Study SHP609-302.

    Subject analysis set title
    Idursulfase-IT 10 mg, Former Substudy
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Former Substudy group included participants who received IT treatment 5-10 mg in HGT-HIT-094 substudy.

    Subject analysis sets values
    		 Idursulfase-IT 10 mg, Delayed IT Idursulfase-IT 10 mg, Early IT Idursulfase-IT 10 mg, Former Substudy
    Number of subjects
    15
    32
    9
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    6.31 ( 2.678 )
    4.90 ( 1.414 )
    2.48 ( 0.483 )
    Gender categorical
    Units: Subjects
        Male
    15
    32
    9
        Female
    0
    0
    0
    Race
    Units: Subjects
        Asian
    0
    4
    0
        Black or African American
    0
    1
    0
        White
    12
    21
    8
        Other
    3
    6
    1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    5
    8
    1
        Not Hispanic or Latino
    8
    23
    7
        Not Reported
    2
    1
    1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Idursulfase-IT
    Reporting group description
    		 Participants received 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with elaprase for 480 weeks. Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (>8 months to 30 months of age) or 10 mg (>30 months to 3 years of age) of idursulfase-IT.

    Subject analysis set title
    Idursulfase-IT 10 mg, Delayed IT
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Delayed IT group included participants who were randomised to the no IT treatment cohort in Study HGT-HIT-094 and began IT treatment in Study SHP609-302.

    Subject analysis set title
    Idursulfase-IT 10 mg, Early IT
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Early IT group included participants who were randomised to the IT treatment cohort in Study HGT-HIT-094 and continued in Study SHP609-302.

    Subject analysis set title
    Idursulfase-IT 10 mg, Former Substudy
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The Former Substudy group included participants who received IT treatment 5-10 mg in HGT-HIT-094 substudy.

    Primary: Number of Participants With Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events (AEs) [1]
    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 investigational product-related. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial).
    End point type
    Primary
    End point timeframe
    Up to 9 years
    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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    56
    Units: participants
    56
    No statistical analyses for this end point

    Primary: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, and 12-lead Electrocardiogram (ECG) Findings

    		 Close Top of page
    End point title
    		 Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, and 12-lead Electrocardiogram (ECG) Findings [2]
    End point description
    Number of participants with clinically significant changes in vital signs (the injection [IT] vital signs and regular vital signs (temperature, pulse, blood pressure [systolic and diastolic], oxygen saturation, and respiration rate), laboratory parameters (chemistry, hematology, urinalysis and CSF values), and 12-lead ECG findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial).
    End point type
    Primary
    End point timeframe
    Up to 9 years
    Notes
    [2] - 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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    56
    Units: participants
        Vital Signs
    0
        Laboratory Parameters
    0
        12-lead ECG
    0
    No statistical analyses for this end point

    Primary: Maximum Observed Serum Concentration (Cmax) of Idursulfase

    		 Close Top of page
    End point title
    		 Maximum Observed Serum Concentration (Cmax) of Idursulfase [3]
    End point description
    Idursulfase concentrations in serum were determined using a validated Enzyme -Linked Immunosorbent Assay (ELISA) method. Concentration for Cmax is presented in this endpoint. The Pharmacokinetic Population included all the participants in Study SHP609-302 who received study drug and participated in the scheduled pharmacokinetic studies, and for whom at least 1 postdose pharmacokinetic blood sample was collected. Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Primary
    End point timeframe
    Predose and multiple time points post-dose at Week 100
    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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT 10 mg, Delayed IT Idursulfase-IT 10 mg, Early IT Idursulfase-IT 10 mg, Former Substudy
    Number of subjects analysed
    10
    20
    3
    Units: nanogram per millilitre (ng/mL)
        arithmetic mean (standard deviation)
    128.19 ( 169.427 )
    104.89 ( 66.879 )
    120.23 ( 57.308 )
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in CSF at Month 67

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in CSF at Month 67 [4]
    End point description
    The percent change in concentration of GAG in CSF was assessed. The Pharmacokinetic Population included all the participants in Study SHP609-302 who received study drug and participated in the scheduled pharmacokinetic studies, and for whom at least 1 postdose pharmacokinetic blood sample was collected. Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Primary
    End point timeframe
    Baseline, Month 67
    Notes
    [4] - 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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    27
    Units: percent change
        arithmetic mean (standard deviation)
    -71.15 ( 17.842 )
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in the Concentration of GAG in Urine at Month 67

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in the Concentration of GAG in Urine at Month 67 [5]
    End point description
    The percent change in concentration of GAG in urine was assessed. The Pharmacokinetic Population included all the participants in Study SHP609-302 who received study drug and participated in the scheduled pharmacokinetic studies, and for whom at least 1 postdose pharmacokinetic blood sample was collected. Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Primary
    End point timeframe
    Baseline, Month 67
    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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    23
    Units: percent change
        arithmetic mean (standard deviation)
    -32.44 ( 29.366 )
    No statistical analyses for this end point

    Primary: Number of Participants who Reported Positive for Anti-idursulfase Antibodies in CSF

    		 Close Top of page
    End point title
    		 Number of Participants who Reported Positive for Anti-idursulfase Antibodies in CSF [6]
    End point description
    The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial).
    End point type
    Primary
    End point timeframe
    Up to 9 years
    Notes
    [6] - 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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    56
    Units: participants
    25
    No statistical analyses for this end point

    Primary: Number of Participants who Reported Positive for Anti-idursulfase Antibodies in Serum

    		 Close Top of page
    End point title
    		 Number of Participants who Reported Positive for Anti-idursulfase Antibodies in Serum [7]
    End point description
    The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial).
    End point type
    Primary
    End point timeframe
    Up to 9 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 analysis was planned for this endpoint.
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    56
    Units: participants
    46
    No statistical analyses for this end point

    Secondary: Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Standard Cluster Scores at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Standard Cluster Scores at Month 67
    End point description
    DAS-II was used to assess all participants of age 2 years, 6 months or older. DAS-II comprises 2 overlapping batteries. Early Years battery (EYB) was designed for children ages 2 years, 6 months through 6 years, 11 months. The School Age Battery (SAB) was designed for children ages 7 years, 0 months through 17 years, 11months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The cluster areas include general conceptual ability (GCA), verbal, nonverbal, spatial, and special nonverbal composite (SNC). The cluster area score represents a score (mean=100 and standard deviation=15) on which higher scores=higher level of cognitive ability. Number of subjects analysed indicates the number of participants with data available for analyses. ‘n’ indicates the number of participants with data available for analyses for specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    3
    Units: score on a scale
    arithmetic mean (standard deviation)
        GCA (n=2)
    -6.0 ( 8.49 )
        Verbal (n=3)
    -23.7 ( 21.59 )
        Nonverbal (n=2)
    -20.5 ( 7.78 )
        Spatial (n=3)
    0.3 ( 18.88 )
        SNC (n=2)
    -5.5 ( 6.36 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Standard Scores of the Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) Domains at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in Standard Scores of the Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) Domains at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialisation, motor skills, and the adaptive behaviour composite [ABC] (a composite of the other 4 domains). The standard scores represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        Communication
    -13.5 ( 4.95 )
        Daily Living Skills
    -9.5 ( 0.71 )
        Socialisation
    -14.5 ( 9.19 )
        Motor Skills
    11.5 ( 7.78 )
        ABC
    -13.5 ( 2.12 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Standard Composite Scores of the VABS-II Domains at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in Standard Composite Scores of the VABS-II Domains at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialisation, motor skills, and the ABC (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants available for analyses. ‘n’ indicates the number of participants with data available for analyses for specified category. ‘999’ indicates that no participants were analysed in the specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline Age < 6 Years (n=2)
    -13.5 ( 2.12 )
        Baseline Age ≥ 6 Years (n=0)
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Age Equivalents Score of the Differential Ability Scales, Second Edition (DAS-II) at Month 61

    		 Close Top of page
    End point title
    		 Change From Baseline in Age Equivalents Score of the Differential Ability Scales, Second Edition (DAS-II) at Month 61
    End point description
    DAS-II comprises 2 overlapping batteries; EYB= 2 years,6 months through 6 years,11 months and SAB=7 years,0 months through 17 years,11 months. Core subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices and Copying for DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for DAS-II School Years. Standardized scores were converted to age equivalent scores (AES) to measure ability, skill, and knowledge expressed as age at which most individuals reach same level. Higher score (HS)= greater cognitive ability (CA). Subtests score represent a score (mean=50 and standard deviation of 10) on which HS=higher level of CA. Number of subjects analysed=participants with data available for analyses. ‘n’=participants with data available for analyses for specified category.'999'=standard deviation not estimable for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 61
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        EYB: Verbal Comprehension (n=2)
    1.50 ( 1.768 )
        EYB: Picture Similarities (n=2)
    2.63 ( 2.652 )
        EYB: Naming Vocabulary (n=2)
    3.13 ( 1.237 )
        EYB: Pattern Construction (n=2)
    1.38 ( 1.237 )
        EYB: Matrices (n=2)
    3.38 ( 1.237 )
        EYB: Copying (n=2)
    1.13 ( 1.591 )
        SAB: Recall of Designs (n=1)
    0.00 ( 999 )
        SAB: Word Definitions (n=1)
    -0.25 ( 999 )
        SAB: Pattern Construction (n=1)
    0.00 ( 999 )
        SAB: Matrices (n=1)
    2.50 ( 999 )
        SAB: Verbal Similarities (n=1)
    0.00 ( 999 )
        SAB: Sequential & Quantitative Reasoning (n=1)
    0.75 ( 999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Developmental Quotients (DQ) of the DAS-II at Month 61

    		 Close Top of page
    End point title
    		 Change From Baseline in Developmental Quotients (DQ) of the DAS-II at Month 61
    End point description
    DAS-II was used to assess all participants of age 2 years, 6 months or older. DAS-II comprises 2 overlapping batteries. EYB was designed for children ages 2 years, 6 months through 6 years, 11 months. The SAB was designed for children ages 7 years, 0 months through 17 years, 11 months. The core subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. The DQ was computed as a ratio and expressed as a percentage using the AES divided by the age at testing ([AES/chronological age] × 100; range, 0-100). Number of subjects analysed is the number of participants with data available for analyses. ‘n’=participants with data available for analysis for specified category. '999'=standard deviation not estimable for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 61
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        EYB: Verbal Comprehension (n=2)
    -27.45 ( 13.223 )
        EYB: Picture Similarities (n=2)
    -7.75 ( 23.971 )
        EYB: Naming Vocabulary (n=2)
    -10.95 ( 4.596 )
        EYB: Pattern Construction (n=2)
    -22.25 ( 7.425 )
        EYB: Matrices (n=2)
    -9.20 ( 12.021 )
        EYB: Copying (n=2)
    -34.95 ( 15.627 )
        SAB: Recall of Designs (n=1)
    -25.90 ( 999 )
        SAB: Word Definitions (n=1)
    -29.30 ( 999 )
        SAB: Pattern Construction (n=1)
    -28.50 ( 999 )
        SAB: Matrices (n=1)
    2.20 ( 999 )
        SAB: Verbal Similarities (n=1)
    -25.90 ( 999 )
        SAB: Sequential & Quantitative Reasoning (n=1)
    -19.80 ( 999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in T-scores of the Core Subtests DAS-II at Month 61

    		 Close Top of page
    End point title
    		 Change From Baseline in T-scores of the Core Subtests DAS-II at Month 61
    End point description
    DAS-II was used to assess all participants of age 2 years, 6 months or older. DAS-II comprises 2 overlapping batteries. EYB was designed for children ages 2 years, 6 months through 6 years, 11 months. SAB was designed for children ages 7 years, 0 months through 17 years, 11months.The CS include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. CS score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. Number of subjects analysed=participants with data available for analyses. ‘n’=participants with data available for analyses for specified category. '999'=standard deviation not estimable for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 61
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        EYB: Verbal Comprehension (n=2)
    -14.5 ( 9.19 )
        EYB: Picture Similarities (n=2)
    -6.5 ( 10.61 )
        EYB: Naming Vocabulary (n=2)
    -8.5 ( 4.95 )
        EYB: Pattern Construction (n=2)
    -10.0 ( 9.90 )
        EYB: Matrices (n=2)
    2.5 ( 2.12 )
        EYB: Copying (n=2)
    -14.0 ( 26.87 )
        SAB: Recall of Designs (n=1)
    -4.0 ( 999 )
        SAB: Word Definitions (n=1)
    -28.0 ( 999 )
        SAB: Pattern Construction (n=1)
    -13.0 ( 999 )
        SAB: Matrices (n=1)
    -3.0 ( 999 )
        SAB: Verbal Similarities (n=1)
    -24.0 ( 999 )
        SAB: Sequential & Quantitative Reasoning (n=1)
    -2.0 ( 999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Age Equivalents Score of the VABS-II Sub Domains at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in Age Equivalents Score of the VABS-II Sub Domains at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialisation (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The mean age equivalent score was obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound). The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        Communication: Receptive
    2.13 ( 0.412 )
        Communication: Expressive
    2.54 ( 1.591 )
        Communication: Written
    1.58 ( 1.296 )
        Daily Living Skills: Personal
    4.50 ( 1.296 )
        Daily Living Skills: Domestic
    3.42 ( 0.825 )
        Daily Living Skills: Community
    1.83 ( 0.943 )
        Socialisation: Interpersonal Relationships
    1.92 ( 4.832 )
        Socialisation: Play and Leisure Time
    2.25 ( 1.768 )
        Socialisation: Coping Skills
    0.75 ( 1.296 )
        Motor Skills: Gross
    9.75 ( 8.721 )
        Motor Skills: Fine
    2.33 ( 0.118 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in DQ of the VABS-II Sub Domains at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in DQ of the VABS-II Sub Domains at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialisation (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0-100). The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        Communication: Receptive
    -7.30 ( 19.375 )
        Communication: Expressive
    -6.65 ( 23.547 )
        Communication: Written
    -40.15 ( 10.677 )
        Daily Living Skills: Personal
    9.50 ( 13.011 )
        Daily Living Skills: Domestic
    -22.60 ( 0.424 )
        Daily Living Skills: Community
    -27.15 ( 16.900 )
        Socialisation: Interpersonal Relationships
    -26.00 ( 44.265 )
        Socialisation: Play and Leisure Time
    -18.00 ( 13.435 )
        Socialisation: Coping Skills
    -44.65 ( 31.183 )
        Motor Skills: Gross
    47.35 ( 66.539 )
        Motor Skills: Fine
    -19.90 ( 6.788 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in v-Scores of the VABS-II Sub Domains at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in v-Scores of the VABS-II Sub Domains at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialisation (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The V-scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    2
    Units: score on a scale
    arithmetic mean (standard deviation)
        Communication: Receptive
    -0.5 ( 2.12 )
        Communication: Expressive
    -1.0 ( 2.83 )
        Communication: Written
    -8.0 ( 2.83 )
        Daily Living Skills: Personal
    1.0 ( 1.41 )
        Daily Living Skills: Domestic
    -2.0 ( 1.41 )
        Daily Living Skills: Community
    -5.0 ( 1.41 )
        Socialisation: Interpersonal Relationships
    -3.0 ( 5.66 )
        Socialisation: Play and Leisure Time
    -2.0 ( 1.41 )
        Socialisation: Coping Skills
    -3.5 ( 2.12 )
        Motor Skills: Gross
    2.5 ( 2.12 )
        Motor Skills: Fine
    1.5 ( 0.71 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in v-Scale Scores of the VABS-II Maladaptive Behaviour Index and its Subscales at Month 67

    		 Close Top of page
    End point title
    		 Change From Baseline in v-Scale Scores of the VABS-II Maladaptive Behaviour Index and its Subscales at Month 67
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The maladaptive behaviour index is a composite of the internalizing, externalizing, and other types of undesirable behaviour that may interfere with the individual’s adaptive functioning. The v-Scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses. '999'=standard deviation not estimable for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 67
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    1
    Units: score on a scale
    arithmetic mean (standard deviation)
        Maladaptive Behaviour Index
    -3.0 ( 999 )
        Internalizing
    -4.0 ( 999 )
        Externalizing
    -1.0 ( 999 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Observed Maladaptive Levels of the VABS-II Maladaptive Behaviour Index and its Subscales at Month 61

    		 Close Top of page
    End point title
    		 Number of Participants With Observed Maladaptive Levels of the VABS-II Maladaptive Behaviour Index and its Subscales at Month 61
    End point description
    The VABS-II test measures adaptive behaviours, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The maladaptive behaviour index is a composite of the internalizing, externalizing, and other types of undesirable behaviour that may interfere with the individual’s adaptive functioning. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses. Only categories having non-zero values are reported.
    End point type
    Secondary
    End point timeframe
    Month 61
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    47
    Units: count of participants
        Maladaptive Behaviour Index; Average
    7
        Maladaptive Behaviour Index; Elevated
    1
        Internalizing; Average
    6
        Internalizing; Elevated
    2
        Externalizing; Average
    2
        Externalizing; Elevated
    6
    No statistical analyses for this end point

    Secondary: Change From Baseline in Brain Structure Volume as Measured by Magnetic Resonance Imaging (MRI)

    		Close Top of page
    End point title
    		 Change From Baseline in Brain Structure Volume as Measured by Magnetic Resonance Imaging (MRI)
    End point description
    Brain structure volume was assessed from brain total intracranial volume, brain total tissue volume, brain total white matter, brain total gray matter, and total CSF volume as measured by MRI. The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial). Number of subjects analysed indicates the number of participants with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, End of Study (final assessment post Month 109)
    End point values
    		 Idursulfase-IT
    Number of subjects analysed
    3
    Units: cubic centimetres (cm^3)
    arithmetic mean (standard deviation)
        Brain Total Intracranial Volume
    -19.813 ( 70.994 )
        Brain Total Tissue Volume
    -38.573 ( 134.021 )
        Brain Total White Matter Volume
    98.180 ( 64.194 )
        Brain Total Gray Matter Volume
    -136.750 ( 79.547 )
        Total CSF Volume
    58.480 ( 52.382 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 9 years
    Adverse event reporting additional description
    The Safety Population included all the participants in Study SHP609-302 who underwent IDDD implantation or received at least 1 dose of study drug (full or partial).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Idursulfase-IT
    Reporting group description
    		 Participants received 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with elaprase for 480 weeks. Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (>8 months to 30 months of age) or 10 mg (>30 months to 3 years of age) of idursulfase-IT.

    Serious adverse events
    		 Idursulfase-IT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    48 / 56 (85.71%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Device kink
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Device failure
         subjects affected / exposed
    22 / 56 (39.29%)
         occurrences causally related to treatment / all
    0 / 32
         deaths causally related to treatment / all
    0 / 0
    Device extrusion
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device dislocation
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Device deployment issue
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device breakage
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular complication associated with device
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences causally related to treatment / all
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    Medical device site reaction
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injection site swelling
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Inflammation
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Implant site effusion
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device misuse
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Testicular torsion
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Adenoidal hypertrophy
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sleep disorder
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staring
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Albumin CSF increased
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CSF cell count increased
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CSF glucose decreased
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CSF lymphocyte count increased
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CSF protein increased
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CSF white blood cell count
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcus test positive
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Foreign body aspiration
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural nausea
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural pain
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Procedural vomiting
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pseudomeningocele
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Aortic valve stenosis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences causally related to treatment / all
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    Convulsion
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleocytosis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Dental caries
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Toothache
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis reactive
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Catheter site cellulitis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Central nervous system infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Corona virus infection
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Implant site abscess
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Implant site infection
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Meningitis streptococcal
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nocardiosis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Stenotrophomonas infection
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 56 (1.79%)
         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
    		 Idursulfase-IT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 56 (100.00%)
    Vascular disorders
    Diastolic hypertension
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    8
    Systolic hypertension
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    8
    Flushing
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Hypertension
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Hypotension
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    6
    Diastolic hypotension
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    8
    General disorders and administration site conditions
    Medical device complication
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    13
    Irritability
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    12
    Pain
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    14
    Pyrexia
         subjects affected / exposed
    43 / 56 (76.79%)
         occurrences all number
    168
    Vascular complication associated with device
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    15
    Catheter site effusion
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    8
    Catheter site erythema
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Catheter site extravasation
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Catheter site pain
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    5
    Catheter site swelling
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    8
    Device breakage
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Device malfunction
         subjects affected / exposed
    17 / 56 (30.36%)
         occurrences all number
    41
    Device occlusion
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    14
    Face oedema
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Fatigue
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Gait disturbance
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    19
    Implant site effusion
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    9
    Implant site swelling
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Influenza like illness
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Infusion site swelling
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Medical device pain
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Hypersensitivity
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Seasonal allergy
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    9
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Bronchospasm
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Choking
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Cough
         subjects affected / exposed
    40 / 56 (71.43%)
         occurrences all number
    148
    Epistaxis
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    10
    Nasal congestion
         subjects affected / exposed
    24 / 56 (42.86%)
         occurrences all number
    61
    Oropharyngeal pain
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    10
    Productive cough
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    7
    Pulmonary oedema
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Respiratory distress
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Rhinorrhoea
         subjects affected / exposed
    25 / 56 (44.64%)
         occurrences all number
    63
    Sleep apnoea syndrome
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Upper respiratory tract congestion
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Upper-airway cough syndrome
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Wheezing
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    12
    Adenoidal hypertrophy
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    7
    Insomnia
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    7
    Dysphemia
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    9
    Attention deficit/hyperactivity disorder
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    6
    Anxiety
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    14
    Agitation
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    10
    Aggression
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    13
    Abnormal behaviour
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    15
    Staring
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    19
    Albumin CSF increased
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    17
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Blood bicarbonate decreased
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    15
    Blood calcium decreased
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Blood pressure diastolic decreased
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    45
    Blood pressure diastolic increased
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    24
    Blood pressure increased
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Blood pressure systolic decreased
         subjects affected / exposed
    14 / 56 (25.00%)
         occurrences all number
    46
    White blood cell count decreased
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    6
    Red blood cells CSF positive
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    13
    Red blood cell count decreased
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    10
    Platelet count decreased
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    7
    Oxygen saturation decreased
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    27
    Nuclear magnetic resonance imaging brain abnormal
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Neutrophil count increased
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    9
    Neutrophil count decreased
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Heart rate increased
         subjects affected / exposed
    15 / 56 (26.79%)
         occurrences all number
    40
    Heart rate decreased
         subjects affected / exposed
    15 / 56 (26.79%)
         occurrences all number
    67
    Haemoglobin decreased
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    10
    Haematocrit decreased
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    13
    Eosinophil percentage increased
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    15
    Eosinophil count increased
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    29
    Electrocardiogram QT prolonged
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    7
    Coronavirus test positive
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Cardiac murmur
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Carbon dioxide decreased
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    12
    CSF white blood cell count increased
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    37
    CSF test abnormal
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    CSF protein increased
         subjects affected / exposed
    20 / 56 (35.71%)
         occurrences all number
    56
    CSF neutrophil count increased
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    CSF glucose decreased
         subjects affected / exposed
    16 / 56 (28.57%)
         occurrences all number
    45
    CSF cell count increased
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    30
    Body temperature decreased
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    24
    Blood uric acid increased
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Blood triglycerides increased
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    14
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    7
    Blood pressure systolic increased
         subjects affected / exposed
    14 / 56 (25.00%)
         occurrences all number
    43
    White blood cell count increased
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    12
    Contusion
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    18
    Excoriation
         subjects affected / exposed
    14 / 56 (25.00%)
         occurrences all number
    32
    Fall
         subjects affected / exposed
    17 / 56 (30.36%)
         occurrences all number
    33
    Head injury
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Incision site oedema
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    10
    Incision site pain
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Joint injury
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Laceration
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    12
    Ligament sprain
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Post procedural haemorrhage
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Procedural headache
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Procedural hypertension
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    35
    Procedural hypotension
         subjects affected / exposed
    13 / 56 (23.21%)
         occurrences all number
    39
    Procedural nausea
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Procedural pain
         subjects affected / exposed
    33 / 56 (58.93%)
         occurrences all number
    65
    Procedural vomiting
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    9
    Pseudomeningocele
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Scratch
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Thermal burn
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Tooth fracture
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Congenital, familial and genetic disorders
    Foramen magnum stenosis
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Developmental hip dysplasia
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Sinus tachycardia
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    16
    Tachycardia
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Nervous system disorders
    Psychomotor hyperactivity
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    6
    Nerve compression
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Lethargy
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    9
    Headache
         subjects affected / exposed
    27 / 56 (48.21%)
         occurrences all number
    98
    Febrile convulsion
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Cerebrospinal fluid retention
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Carpal tunnel syndrome
         subjects affected / exposed
    16 / 56 (28.57%)
         occurrences all number
    19
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Eosinophilia
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Ear and labyrinth disorders
    Motion sickness
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Cerumen impaction
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Deafness
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    7
    Ear pain
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    10
    Middle ear effusion
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Otorrhoea
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    47
    Tympanic membrane perforation
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Eye disorders
    Astigmatism
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Conjunctivitis
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    8
    Eye swelling
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Ocular hyperaemia
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Gastrointestinal disorders
    Umbilical hernia
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Abdominal pain
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    10
    Abdominal pain upper
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Constipation
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    18
    Dental caries
         subjects affected / exposed
    15 / 56 (26.79%)
         occurrences all number
    19
    Diarrhoea
         subjects affected / exposed
    30 / 56 (53.57%)
         occurrences all number
    86
    Frequent bowel movements
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Haematochezia
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Nausea
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    19
    Retching
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Toothache
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    6
    Vomiting
         subjects affected / exposed
    40 / 56 (71.43%)
         occurrences all number
    182
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Dermatitis allergic
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    5
    Dermatitis contact
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    17
    Dermatitis diaper
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    13
    Dry skin
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Eczema
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Erythema
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    11
    Rash
         subjects affected / exposed
    16 / 56 (28.57%)
         occurrences all number
    22
    Rash erythematous
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Rash generalised
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Rash macular
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    9
    Rash maculo-papular
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    9
    Red man syndrome
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Scab
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    4
    Swelling face
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Urticaria
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    17
    Renal and urinary disorders
    Enuresis
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Proteinuria
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Toe walking
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    8
    Spondylolisthesis
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Spinal disorder
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Scoliosis
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Pain in extremity
         subjects affected / exposed
    17 / 56 (30.36%)
         occurrences all number
    37
    Neck pain
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    6
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Foot deformity
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    6
    Back pain
         subjects affected / exposed
    16 / 56 (28.57%)
         occurrences all number
    26
    Arthralgia
         subjects affected / exposed
    9 / 56 (16.07%)
         occurrences all number
    14
    Achilles tendon discomfort
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Tooth infection
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    8
    Corona virus infection
         subjects affected / exposed
    17 / 56 (30.36%)
         occurrences all number
    22
    Croup infectious
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    6
    Ear infection
         subjects affected / exposed
    32 / 56 (57.14%)
         occurrences all number
    103
    Fungal skin infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Gastroenteritis
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    13
    Gastroenteritis viral
         subjects affected / exposed
    14 / 56 (25.00%)
         occurrences all number
    23
    Hand-foot-and-mouth disease
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Influenza
         subjects affected / exposed
    18 / 56 (32.14%)
         occurrences all number
    26
    Laryngitis
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    8
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    10
    Metapneumovirus infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Nasopharyngitis
         subjects affected / exposed
    38 / 56 (67.86%)
         occurrences all number
    126
    Oral herpes
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    6
    Otitis externa
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    8
    Otitis media
         subjects affected / exposed
    21 / 56 (37.50%)
         occurrences all number
    57
    Otitis media acute
         subjects affected / exposed
    12 / 56 (21.43%)
         occurrences all number
    16
    Pharyngitis
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    11
    Pharyngitis streptococcal
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    12
    Pneumonia
         subjects affected / exposed
    7 / 56 (12.50%)
         occurrences all number
    8
    Respiratory syncytial virus infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    3
    Respiratory tract infection
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    9
    Rhinitis
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    19
    Sinusitis
         subjects affected / exposed
    11 / 56 (19.64%)
         occurrences all number
    29
    Staphylococcal infection
         subjects affected / exposed
    3 / 56 (5.36%)
         occurrences all number
    4
    Tinea pedis
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    5
    Tooth abscess
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    8
    Bronchitis
         subjects affected / exposed
    5 / 56 (8.93%)
         occurrences all number
    7
    Upper respiratory tract infection
         subjects affected / exposed
    37 / 56 (66.07%)
         occurrences all number
    85
    Urinary tract infection
         subjects affected / exposed
    4 / 56 (7.14%)
         occurrences all number
    6
    Viral infection
         subjects affected / exposed
    8 / 56 (14.29%)
         occurrences all number
    9
    Metabolism and nutrition disorders
    Iron deficiency
         subjects affected / exposed
    6 / 56 (10.71%)
         occurrences all number
    6
    Decreased appetite
         subjects affected / exposed
    10 / 56 (17.86%)
         occurrences all number
    12

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 May 2016
    The following changes were made as per Amendment 2: 1. Extended the treatment duration in the study to 5 years. 2. Specified the maximum volume of blood collected from a participant by study visit.
    28 Feb 2017
    The following changes were made as per Amendment 3: 1. Added the option of same-day administration of IV ELAPRASE and idursulfase-IT for participants who had already completed at least 12 months of idursulfase-IT treatment in studies HGT-HIT-094 or SHP609-302. 2. Additional pharmacokinetic assessments were implemented to measure any increase in total systemic exposure to idursulfase under the same-day administration regime. 3. A new category of AE relatedness, related to IV ELAPRASE and/or idursulfase-IT, was added to facilitate the collection and analysis of AEs observed with same-day administration.
    09 Oct 2018
    The following changes were made as per Amendment 4: 1. Extended the duration of treatment from a maximum of 5 years to a maximum of 10 years. 2. A description of the lower and upper levels of the Early Years battery for DAS-II was added. 3. A strategy for data integration was added. 4. Language was added regarding planned subgroup analyses.

    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, Contact us.
    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.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA