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    Clinical Trial Results:
    A Phase I/II Safety, Tolerability, Ascending Dose and Dose Frequency Study of Recombinant Human Heparan-N-sulfatase (rhHNS) Intrathecal Administration via an Intrathecal Drug Delivery Device in Patients with Sanfilippo Syndrome Type A (MPS IIIA)

    Summary
    EudraCT number
    2009-015984-15
    Trial protocol
    GB  
    Global end of trial date
    10 Sep 2012

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Jul 2018
    First version publication date
    13 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    HGT-SAN-055
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01155778
    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
    Olivia Maurel, Shire Human Genetic Therapies AB, 41 224194150, omaurel@shire.com
    Scientific contact
    Olivia Maurel, Shire Human Genetic Therapies AB, 41 224194150, omaurel@shire.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001634-PIP01-14
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Sep 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Sep 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the safety and tolerability of recombinant human heparan-N-sulfatase (rhHNS) (HGT-1410) via ascending doses administered via a surgically implanted intrathecal drug delivery device (IDDD) once monthly for 6 months, in subjects with Mucopolysaccharidosis IIIA or Sanfilippo Syndrome Type A (MPS IIIA).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that had their origin in the Declaration of Helsinki and that were consistent with Good Clinical Practice (GCP) and applicable regulatory requirements. Known instances of non-conformance were documented and were not considered to have had an impact on the overall conclusions of this study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Jul 2010
    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
    Netherlands: 6
    Country: Number of subjects enrolled
    United Kingdom: 6
    Worldwide total number of subjects
    12
    EEA total number of subjects
    12
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    7
    Adolescents (12-17 years)
    3
    Adults (18-64 years)
    2
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Study enrolled 12 subjects and 4 subjects were included in each of the 3 dose groups.

    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
    HGT-1410 10 mg
    Arm description
    HGT-1410/rhHNS 10 milligram (mg) monthly via an intrathecal drug delivery device (IDDD) (every 28 [±7 days]) for a total of 6 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Recombinant human heparan N-sulfatase
    Investigational medicinal product code
    HGT-1410
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 [±7 days]) for a total of 6 months.

    Arm title
    HGT-1410 90 mg
    Arm description
    HGT-1410/rhHNS 45 mg dose every 14 [±2 days] for a monthly total dose of 90 mg via an IDDD for 6 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Recombinant human heparan N-sulfatase
    Investigational medicinal product code
    HGT-1410
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    HGT-1410/rhHNS 45 mg dose every 14 [±2 days] for a monthly total dose of 90 mg via an IDDD for 6 months.

    Arm title
    HGT-1410 45 mg
    Arm description
    HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 [±7 days]) for a total of 6 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Recombinant human heparan N-sulfatase
    Investigational medicinal product code
    HGT-1410
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 [±7 days]) for a total of 6 months.

    Number of subjects in period 1
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Started
    4
    4
    4
    Completed
    4
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    HGT-1410 10 mg
    Reporting group description
    HGT-1410/rhHNS 10 milligram (mg) monthly via an intrathecal drug delivery device (IDDD) (every 28 [±7 days]) for a total of 6 months.

    Reporting group title
    HGT-1410 90 mg
    Reporting group description
    HGT-1410/rhHNS 45 mg dose every 14 [±2 days] for a monthly total dose of 90 mg via an IDDD for 6 months.

    Reporting group title
    HGT-1410 45 mg
    Reporting group description
    HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 [±7 days]) for a total of 6 months.

    Reporting group values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg Total
    Number of subjects
    4 4 4 12
    Age categorical
    Units: Subjects
        Less than equal to (<=) 18 years
    3 3 4 10
        Between 18 and 65 years
    1 1 0 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    9.15 ± 4.7 10.64 ± 8.7 9.07 ± 9.8 -
    Gender, Male/Female
    Units: 0x
        Female
    1 1 2 4
        Male
    3 3 2 8

    End points

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    End points reporting groups
    Reporting group title
    HGT-1410 10 mg
    Reporting group description
    HGT-1410/rhHNS 10 milligram (mg) monthly via an intrathecal drug delivery device (IDDD) (every 28 [±7 days]) for a total of 6 months.

    Reporting group title
    HGT-1410 90 mg
    Reporting group description
    HGT-1410/rhHNS 45 mg dose every 14 [±2 days] for a monthly total dose of 90 mg via an IDDD for 6 months.

    Reporting group title
    HGT-1410 45 mg
    Reporting group description
    HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 [±7 days]) for a total of 6 months.

    Primary: Number of Treatment Emergent Serious Adverse Events (SAE)

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    End point title
    Number of Treatment Emergent Serious Adverse Events (SAE) [1]
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation subject administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as all adverse events (AEs) from the time of the surgery for IDDD implantation to the last follow up contact, 30 (±7) days after the end of study (EOS) procedures. Safety population was defined as all enrolled subjects who received at least 1 dose (full or partial) of study drug.
    End point type
    Primary
    End point timeframe
    Baseline to week 30 (follow-up)
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: events
        number (not applicable)
    5
    2
    3
    No statistical analyses for this end point

    Primary: Number of Treatment Emergent Adverse Events (TEAE)

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    End point title
    Number of Treatment Emergent Adverse Events (TEAE) [2]
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation subject administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as all adverse events (AEs) from the time of the surgery for IDDD implantation to the last follow up contact, 30 (±7) days after the end of study (EOS) procedures. Safety population.
    End point type
    Primary
    End point timeframe
    Baseline to week 30 (follow-up)
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: events
        number (not applicable)
    71
    55
    42
    No statistical analyses for this end point

    Primary: Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group

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    End point title
    Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group [3]
    End point description
    Subjects with positive, negative and missing status were reported. Intent to treat (ITT) population was defined as all enrolled subjects who received at least 1 dose (full or partial) of study drug.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: subjects
    number (not applicable)
        Negative (Baseline)
    4
    4
    4
        Positive (Baseline)
    0
    0
    0
        Missing (Baseline)
    0
    0
    0
        Negative (Week 26)
    1
    2
    1
        Positive (Week 26)
    0
    0
    0
        Missing (Week 26)
    3
    2
    3
    No statistical analyses for this end point

    Primary: Summary of Anti-rhHNS Antibody Status in serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group

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    End point title
    Summary of Anti-rhHNS Antibody Status in serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group [4]
    End point description
    Subjects with positive, negative and missing status were reported. ITT population
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: subjects
    number (not applicable)
        Negative (Baseline)
    4
    3
    3
        Positive (Baseline)
    0
    1
    1
        Missing (Baseline)
    0
    0
    0
        Negative (Week 26)
    1
    2
    2
        Positive (Week 26)
    2
    0
    0
        Missing (Week 26)
    1
    2
    2
    No statistical analyses for this end point

    Primary: Summary of Intrathecal Drug Delivery Device (IDDD) Failures

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    End point title
    Summary of Intrathecal Drug Delivery Device (IDDD) Failures [5]
    End point description
    Subjects with IDDD failures were reported. ITT population.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: subjects
        number (not applicable)
    3
    1
    2
    No statistical analyses for this end point

    Secondary: Change from Baseline in Developmental Quotient (DQ) using Bayley Scales of Infant Development Third Edition (BSID III) and Kaufman Assessment Battery for Children Second Edition (KABC II) at Week 22

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    End point title
    Change from Baseline in Developmental Quotient (DQ) using Bayley Scales of Infant Development Third Edition (BSID III) and Kaufman Assessment Battery for Children Second Edition (KABC II) at Week 22
    End point description
    BSID-III was used to assess the cognitive development, language (receptive and expressive), and motor development (fine and gross), of infants and toddlers, ages 0-42 months. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and is an alternative to BSID-III. BSID-III DQ score is based on the Cognitive domain. The DQ score was calculated from the data obtained from either BSID-III/KABC-II mental age equivalent of the child in months divided by the calendar age in months (multiplied by 100 to give percentage points). Here, n = subjects evaluable for specified category for each arm, respectively. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 2, 4, 4)
    51.91 ± 27.292
    51.87 ± 36.095
    43.24 ± 23.112
        Change at Week 22 (n= 2, 4, 4)
    -13.6 ± 8.886
    -4.91 ± 7.769
    -0.89 ± 4.341
    No statistical analyses for this end point

    Secondary: Change from Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS)

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    End point title
    Change from Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS)
    End point description
    FPSS a questionnaire specific to Sanfilippo-specific disabilities, which assesses: motor function, expressive/speech language, and cognitive function by a parent questionnaire. Total disability score (TDS) is the average of the motor skills (MS), speech abilities (SA), and cognitive function (CF) scores and the lower scores indicate developmental regression. Here, n = subjects evaluable for specified category for each arm, respectively. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22, Week 26
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        MS: Baseline (n= 4, 3, 4)
    2.5 ± 0.58
    3 ± 0
    3 ± 0
        MS: Change at Week 22 (n= 4, 3, 4)
    0.3 ± 0.5
    0 ± 0
    0 ± 0
        MS: Change at Week 26/EOS (n= 2, 2, 3)
    0 ± 0
    0 ± 0
    0 ± 0
        SA: Baseline (n= 4, 3, 4)
    2 ± 0.82
    2 ± 0.82
    2 ± 0
        SA: Change at Week 22 (n= 4, 3, 4)
    -0.5 ± 0.58
    0.3 ± 0.5
    0.3 ± 0.58
        SA: Change at Week 26/EOS (n= 2, 2, 3)
    -0.5 ± 0.71
    0.3 ± 0.58
    0 ± 0
        CF: Baseline (n= 4, 3, 4)
    2.3 ± 0.5
    2.8 ± 0.5
    2.3 ± 0.58
        CF: Change at Week 22 (n= 4, 3, 4)
    0 ± 0
    0 ± 0
    0 ± 0
        CF: Change at Week 26/EOS (n= 2, 2, 3)
    0 ± 0
    0 ± 0
    0 ± 0
        TDS: Baseline (n= 4, 3, 4)
    2.25 ± 0.569
    2.58 ± 0.319
    2.44 ± 0.192
        TDS: Change at Week 22 (n= 4, 3, 4)
    -0.08 ± 0.319
    0.08 ± 0.167
    0.11 ± 0.192
        TDS: Change at Week 26/EOS (n= 2, 2, 3)
    -0.17 ± 0.236
    0.11 ± 0.192
    0 ± 0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS)

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    End point title
    Change from Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS)
    End point description
    Sanfilippo Behavior Rating Scale a parent-scored behavioral inventory measuring: comprehensive language skills, expressive language skills, tantrums, mood and emotions, and other behaviors not otherwise classified. Summary of each scores are the sum of the responses within a given domain for a given subject. Higher values of summary scores indicate undesirable behavior. Here, n = subjects evaluable for specified category for each arm, respectively. 99999 signifies standard deviation not reported as there was only 1 evaluable subject and data was not available for the specific measure. ITT population. Abbreviations: Current Communication (CC), Past Communication (PC), Body Movements (BM), Interaction With Objects (IWO), Activity And Routines (AAR), Emotional Function (EF), Safety-consciousness (SC), Social Interaction (SI), Eye Contact (EC), Comfort Seeking (CS), Self-control/Compliance (SCC), Mood, Anger/Aggression (MAA), Self-gratification (SG)
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        CC: Baseline (n= 4, 4, 2)
    8 ± 5.48
    10 ± 5.66
    6.3 ± 6.85
        CC: Change at Week 22 (n= 4, 4, 2)
    5 ± 13.44
    1.5 ± 2.12
    -0.3 ± 1.26
        CC: Change at Week 26/EOS (n= 3, 2, 2)
    1.3 ± 12.5
    1.5 ± 2.12
    -1 ± 1.41
        PC: Baseline (n= 3, 2, 4)
    7.3 ± 6.03
    11 ± 11.37
    8.5 ± 12.02
        PC: Change at Week 22 (n= 1, 0, 1)
    -8 ± 99999
    0 ± 99999
    99999 ± 99999
        PC: Change at Week 26/EOS (n= 0, 0, 0)
    99999 ± 99999
    99999 ± 99999
    99999 ± 99999
        Orality: Baseline (n= 2, 3, 3)
    7 ± 9.9
    17.3 ± 10.26
    10.3 ± 2.08
        Orality: Change at Week 22 (n= 2, 3, 1)
    2 ± 2.83
    4 ± 99999
    6 ± 5.29
        Orality: Change at Week 26/EOS (n= 1, 1, 1)
    0 ± 99999
    4 ± 99999
    5 ± 99999
        BM: Baseline (n= 4, 4, 2)
    5 ± 4.55
    12 ± 2.83
    2.5 ± 2.08
        BM: Change at Week 22 (n= 3, 4, 2)
    2.3 ± 3.51
    -2 ± 2.83
    2 ± 2.45
        BM: Change at Week 26/EOS (n= 3, 2, 2)
    0.3 ± 1.53
    -2 ± 2.83
    0 ± 0
        IWO: Baseline (n= 4, 3, 4)
    4.5 ± 3.11
    8.5 ± 7.9
    10.3 ± 2.08
        IWO: Change at Week 22 (n= 4, 3, 3)
    3.3 ± 4.27
    -2 ± 3.46
    -2 ± 4.58
        IWO: Change at Week 26/EOS (n= 2, 1, 3)
    1 ± 1.41
    -2 ± 3.46
    -1 ± 99999
        AAR: Baseline (n= 1, 3, 4)
    6 ± 99999
    12.3 ± 9.46
    14.3 ± 3.06
        AAR: Change at Week 22 (n= 1, 3, 4)
    8 ± 99999
    -1.3 ± 6.08
    0.7 ± 0.58
        AAR: Change at Week 26/EOS (n= 0, 1, 3)
    99999 ± 99999
    1.7 ± 2.08
    0 ± 99999
        EF: Baseline (n= 3, 4, 4)
    2 ± 3.46
    7.5 ± 5
    2.5 ± 3.11
        EF: Change at Week 22 (n= 3, 4, 4)
    5.3 ± 1.15
    -2.3 ± 3.5
    0 ± 1.41
        EF: Change at Week 26/EOS (n= 2, 2, 3)
    5 ± 1.41
    -1.31 ± 3.06
    0.5 ± 0.71
        SC: Baseline (n= 4, 4, 4)
    7.8 ± 5.44
    11.5 ± 7.9
    9.5 ± 1.91
        SC: Change at Week 22 (n= 4, 4, 4)
    0.5 ± 1
    -0.8 ± 2.5
    1.8 ± 5.74
        SC: Change at Week 26/EOS (n= 3, 2, 3)
    -1 ± 2.65
    -1 ± 3
    -3 ± 2.83
        Fearfulness: Baseline (n= 3, 3, 3)
    7 ± 7.81
    11 ± 6.08
    10.3 ± 8.74
        Fearfulness: Change at Week 22 (n= 3, 3, 3)
    2.7 ± 1.15
    2 ± 1.73
    -1 ± 5.2
        Fearfulness: Change at Week 26/EOS (n= 2, 1, 3)
    2.5 ± 2.12
    2.3 ± 1.53
    -5 ± 99999
        SI: Baseline (n= 4, 4, 4)
    11 ± 3.37
    14.5 ± 6.76
    12.5 ± 2.38
        SI: Change at Week 22 (n= 4, 3, 4)
    3 ± 4.76
    -0.5 ± 3.7
    0.3 ± 4.04
        SI: Change at Week 26/EOS (n= 3, 2, 3)
    0 ± 8
    -0.7 ± 4.62
    -3.5 ± 4.95
        EC: Baseline (n= 4, 4, 3)
    2.8 ± 3.59
    6.7 ± 5.77
    5.5 ± 3.7
        EC: Change at Week 22 (n= 4, 4, 3)
    1.5 ± 1.73
    -1 ± 2.65
    0 ± 3.27
        EC: Change at Week 26/EOS (n= 3, 2, 3)
    0.3 ± 0.58
    -0.7 ± 3.06
    -2 ± 2.83
        EE: Baseline (n= 2, 4, 4)
    8.5 ± 4.95
    8.3 ± 3.3
    7.3 ± 1.71
        EE: Change at Week 22 (n= 1, 4, 4)
    2 ± 99999
    -0.8 ± 2.87
    -0.5 ± 1.29
        EE: Change at Week 26/EOS (n= 0, 2, 3)
    99999 ± 99999
    0.7 ± 1.15
    -1 ± 1.41
        CS: Baseline (n= 4, 3, 4)
    10.3 ± 5.32
    16.5 ± 6.56
    10.3 ± 3.06
        CS: Change at Week 22 (n= 3, 3, 3)
    1.7 ± 4.73
    -2.3 ± 3.21
    -1.7 ± 3.06
        CS: Change at Week 26/EOS (n= 2, 1, 3)
    0 ± 1.41
    -2.3 ± 3.21
    -1 ± 99999
        Attention: Baseline (n= 4, 4, 4)
    8.3 ± 4.65
    10.5 ± 7.72
    8.8 ± 1.26
        Attention: Change at Week 22 (n= 4, 4, 4)
    1 ± 3.16
    2.3 ± 1.71
    2.5 ± 2.38
        Attention: Change at Week 26/EOS (n= 2, 2, 3)
    1.5 ± 2.12
    3.3 ± 1.15
    0.5 ± 0.71
        SCC: Baseline (n= 4, 4, 4)
    8 ± 4.97
    10 ± 7.3
    7.3 ± 2.22
        SCC: Change at Week 22 (n= 3, 4, 4)
    0.3 ± 4.51
    2 ± 1.83
    3.3 ± 3.2
        SCC: Change at Week 26/EOS (n= 3, 2, 3)
    0.7 ± 4.04
    2.7 ± 1.53
    0.5 ± 0.71
        MAA: Baseline (n= 4, 3, 4)
    5.3 ± 4.11
    17.3 ± 15.65
    9.7 ± 3.51
        MAA: Change at Week 22 (n= 2, 3, 4)
    5.5 ± 7.78
    -0.3 ± 2.5
    3.3 ± 5.13
        MAA: Change at Week 26/EOS (n= 3, 1, 3)
    1.7 ± 3.06
    -0.7 ± 2.89
    4 ± 99999
        SG: Baseline (n= 4, 3, 4)
    0.5 ± 1
    4.5 ± 5.26
    0.3 ± 0.58
        SG: Change at Week 22 (n= 3, 3, 4)
    -0.7 ± 1.15
    -1 ± 4.08
    2 ± 1
        SG: Change at Week 26/EOS (n= 3, 1, 3)
    0.3 ± 0.58
    1 ± 1
    1 ± 99999
    No statistical analyses for this end point

    Secondary: Change from Baseline in Developmental Quotient (DQ) using Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Week 22

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    End point title
    Change from Baseline in Developmental Quotient (DQ) using Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Week 22
    End point description
    VABS-II measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other four domains). The Overall DQ score was calculated from the mean age-equivalent score obtained by averaging out the age equivalent scores for all the sub-domains except for Gross and Fine motor skills. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 4, 4, 4)
    44.78 ± 24.747
    47.71 ± 33.687
    47.24 ± 26.612
        Change at Week 22 (n= 2, 2, 2)
    -11.38 ± 12.478
    -10.18 ± 13.333
    -23.96 ± 10.014
    No statistical analyses for this end point

    Secondary: Change from Baseline in Movement Assessment Battery for Children Second Edition (MABC-2) at Week 26 (EOS)

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    End point title
    Change from Baseline in Movement Assessment Battery for Children Second Edition (MABC-2) at Week 26 (EOS)
    End point description
    Movement Assessment Battery for Children, Second Edition (MABC-II) was to be used to identify, describe and guide the treatment of motor impairment in children from 3.0 to 16:11 years of age. Data was not reported as individual subject listings was only reported.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    Units: units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [6] - Data was not reported as individual subject listings was only reported.
    [7] - Data was not reported as individual subject listings was only reported.
    [8] - Data was not reported as individual subject listings was only reported.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Quality of life (QoL) using Child Health Questionnaire™ Parent Form 50 (CHQ 50) Questions at Week 22 and Week 26 (EOS)

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    End point title
    Change from Baseline in Quality of life (QoL) using Child Health Questionnaire™ Parent Form 50 (CHQ 50) Questions at Week 22 and Week 26 (EOS)
    End point description
    CHQ-PF50 which was designed to measure the physical and psychosocial well-being of children 5 years to 18 years of age, consists of 13 health concepts including 11 multi-item and 2 single item scales: Physical Function (PF), Role/Social-Emotional/Behavioral (REB), Role/Social-Physical (RP), bodily pain (BP), General Behavior (BE), Mental Health (MH), Self Esteem (SE), General Health Perceptions (GH), Change in Health (CH), Parental Impact-Emotional (PE), Parental Impact-Time (PT), Family Activities (FA), and Family Cohesion (FC). Transformed scores for all subscales range from 0 to 100, with a higher score indicating better health. Physical and Psychosocial Summary measures (SM) were scored with the use of norm-based methods that standardize the scores to a mean (± Standard Deviation) of 50 ± 10 on the basis of an assessment of the general United States population. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. 99999= SD not available.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        PF: Baseline (n= 2, 4, 2)
    66.67 ± 47.14
    66.67 ± 23.57
    80.28 ± 35.141
        PF: Change at Week 22 (n= 2, 4, 2)
    -8.33 ± 51.069
    5.56 ± 15.713
    -16.39 ± 23.047
        PF: Change at Week 26/EOS (n= 1, 2, 1)
    33.33 ± 99999
    -11.11 ± 99999
    -24.44 ± 34.57
        RP: Baseline (n= 2, 4, 2)
    66.67 ± 47.14
    66.67 ± 47.14
    50 ± 57.735
        RP: Change at Week 22 (n= 2, 4, 2)
    8.33 ± 11.785
    0 ± 0
    8.33 ± 16.667
        RP: Change at Week 26/EOS (n= 1, 2, 1)
    33.33 ± 99999
    0 ± 99999
    0 ± 0
        BP: Baseline (n= 2, 4, 2)
    90 ± 14.14
    30 ± 0
    67.5 ± 29.86
        BP: Change at Week 22 (n= 2, 4, 2)
    -20 ± 56.57
    45 ± 7.07
    7.5 ± 15
        BP: Change at Week 26/EOS (n= 1, 2, 1)
    20 ± 99999
    50 ± 99999
    0 ± 0
        GH: Baseline (n= 2, 4, 2)
    45.42 ± 2.946
    33.33 ± 23.57
    27.92 ± 21.457
        GH: Change at Week 22 (n= 2, 4, 2)
    -7.75 ± 38.537
    11.25 ± 15.91
    -5.21 ± 10.417
        GH: Change at Week 26/EOS(n= 1, 2, 1)
    17.5 ± 99999
    0 ± 99999
    0 ± 0
        REB: Baseline (n= 2, 4, 2)
    66.67 ± 47.14
    50 ± 70.711
    41.67 ± 50
        REB: Change at Week 22 (n= 2, 4, 2)
    -38.89 ± 86.424
    0 ± 0
    11.11 ± 64.788
        REB: Change at Week 26/EOS (n= 1, 2, 1)
    22.22 ± 99999
    0 ± 99999
    0 ± 0
        BE: Baseline (n= 2, 4, 2)
    62.5 ± 17.678
    45.83 ± 11.785
    61.04 ± 15.296
        BE: Change at Week 22 (n= 2, 4, 2)
    12.08 ± 8.839
    -2.08 ± 2.946
    -2.92 ± 15.716
        BE: Change at Week 26/EOS (n= 1, 2, 1)
    30.83 ± 99999
    -8.33 ± 99999
    -14.37 ± 14.437
        MH: Baseline (n= 2, 4, 2)
    75 ± 7.07
    10 ± 14.14
    68.8 ± 10.31
        MH: Change at Week 22 (n= 2, 4, 2)
    0 ± 21.21
    17.5 ± 17.68
    -2.5 ± 16.58
        MH: Change at Week 26/EOS (n= 1, 2, 1)
    15 ± 99999
    5 ± 99999
    -5 ± 7.07
        SE: Baseline (n= 2, 4, 2)
    62.5 ± 5.893
    47.92 ± 14.731
    61.46 ± 18.122
        SE: Change at Week 22 (n= 2, 4, 2)
    0 ± 11.785
    -4.17 ± 5.893
    -3.13 ± 7.116
        SE: Change at Week 26/EOS (n= 1, 2, 1)
    16.67 ± 99999
    -8.33 ± 99999
    8.33 ± 11.785
        PE: Baseline (n= 2, 4, 2)
    66.67 ± 47.14
    20.83 ± 17.678
    27.08 ± 22.948
        PE: Change at Week 22 (n= 2, 4, 2)
    -8.33 ± 82.496
    4.17 ± 5.893
    -2.08 ± 14.232
        PE: Change at Week 26/EOS (n= 1, 2, 1)
    16.67 ± 99999
    0 ± 99999
    -4.17 ± 5.893
        PT: Baseline (n= 2, 4, 2)
    50 ± 70.711
    5.56 ± 7.857
    33.33 ± 28.689
        PT: Change at Week 22 (n= 2, 4, 2)
    11.11 ± 62.854
    16.67 ± 23.57
    -5.56 ± 26.45
        PT: Change at Week 26/EOS (n= 1, 2, 1)
    44.44 ± 99999
    0 ± 99999
    -5.56 ± 23.57
        FA: Baseline (n= 2, 4, 2)
    56.25 ± 61.872
    10.42 ± 14.731
    42.71 ± 13.767
        FA: Change at Week 22 (n= 2, 4, 2)
    0 ± 58.926
    0 ± 0
    -7.29 ± 13.767
        FA: Change at Week 26/EOS (n= 1, 2, 1)
    16.67 ± 99999
    0 ± 99999
    -6.25 ± 2.946
        FC: Baseline (n= 2, 4, 2)
    57.5 ± 38.89
    15 ± 21.21
    72.5 ± 14.43
        FC: Change at Week 22 (n= 2, 4, 2)
    27.5 ± 38.89
    15 ± 21.21
    -6.3 ± 12.5
        FC: Change at Week 26/EOS (n= 1, 2, 1)
    55 ± 99999
    30 ± 99999
    0 ± 0
        SM Physical: Baseline (n= 2, 4, 2)
    38.44 ± 23.545
    31.27 ± 18.193
    31.62 ± 23.071
        SM Physical: Change at Week 22 (n= 2, 4, 2)
    -4.63 ± 29.276
    9.21 ± 5.095
    -1.82 ± 6.112
        SM Physical: Change at Week 26/EOS (n= 1, 2, 1)
    17.25 ± 99999
    4.96 ± 99999
    -4.99 ± 8.195
        SM Psychosocial: Baseline (n= 2, 4, 2)
    42.16 ± 14.06
    17.57 ± 2.418
    33.8 ± 10.879
        SM Psychosocial: Change at Week 22 (n= 2, 4, 2)
    -1.18 ± 23.341
    2.27 ± 4.972
    -0.26 ± 14.004
        SM Psychosocial:Change at Week 26/EOS (n= 1, 2, 1)
    13.64 ± 99999
    -2.29 ± 99999
    -1.58 ± 2.584
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life (QoL) Using Infant Toddler Quality of Life Questionnaire™ (ITQOL) at Week 22 and Week 26 (EOS)

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    End point title
    Change From Baseline in Quality of Life (QoL) Using Infant Toddler Quality of Life Questionnaire™ (ITQOL) at Week 22 and Week 26 (EOS)
    End point description
    ITQOL was developed for children at least 2 months of age up to 5 years and assesses the physical, mental, and social well being of the child and assesses the quality of the parent/guardian's life. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. 99999 signifies standard deviation not reported as there was only 1 evaluable subject and data was not available for the specific measure. Abbreviation: Overall Health (OH), Physical Abilities (PA), Growth And Development (GAD), Bodily Pain (BP), Temperament And Moods (TAM), General Behavior (GEB), Global Behavior (GLB), Getting Along (GA), General Health Perceptions (GHP), PI-Emotion (PIE), PI-Time (PIT), Family Cohesion (FC).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        OH: Baseline (n= 2, 3, 2)
    80 ± 28.28
    65 ± 49.5
    56.7 ± 49.07
        OH: Change at Week 22 (n= 2, 2, 2)
    0 ± 0
    15 ± 21.21
    -12.5 ± 17.68
        OH: Change at Week 26/EOS (n= 1, 0, 0)
    0 ± 99999
    99999 ± 99999
    99999 ± 99999
        PA: Baseline (n= 2, 3, 2)
    83.35 ± 9.405
    93.35 ± 4.738
    75.57 ± 39.496
        PA: Change at Week 22 (n= 2, 2, 2)
    5 ± 11.738
    -1.7 ± 2.404
    1.65 ± 11.809
        PA: Change at Week 26/EOS (n= 1, 0, 0)
    -3.3 ± 99999
    99999 ± 99999
    99999 ± 99999
        GAD: Baseline (n= 2, 3, 2)
    57.2 ± 18.102
    56.8 ± 6.081
    60.83 ± 25.658
        GAD: Change at Week 22 (n= 2, 2, 2)
    -14.7 ± 28.709
    18.2 ± 0.99
    -22.5 ± 7.071
        GAD: Change at Week 26/EOS (n= 1, 0, 0)
    3.1 ± 99999
    99999 ± 99999
    99999 ± 99999
        BP: Baseline (n= 2, 3, 2)
    95.85 ± 5.869
    62.5 ± 29.416
    58.33 ± 36.294
        BP: Change at Week 22 (n= 2, 2, 2)
    -29.2 ± 17.678
    12.5 ± 41.154
    25 ± 11.738
        BP: Change at Week 26/EOS (n= 1, 0, 0)
    -16.7 ± 99999
    99999 ± 99999
    99999 ± 99999
        TAM: Baseline (n= 2, 3, 2)
    72.2 ± 17.678
    52.8 ± 15.698
    68.97 ± 21.731
        TAM: Change at Week 22 (n= 2, 2, 2)
    -23.6 ± 21.637
    -5.6 ± 19.658
    -2.75 ± 33.446
        TAM: Change at Week 26/EOS (n= 1, 0, 0)
    -12.8 ± 99999
    99999 ± 99999
    99999 ± 99999
        GEB: Baseline (n= 2, 3, 2)
    58.35 ± 32.456
    12.5 ± 5.94
    34.73 ± 17.465
        GEB: Change at Week 22 (n= 2, 2, 2)
    -12.5 ± 8.91
    18.75 ± 0.071
    7.25 ± 25.102
        GEB: Change at Week 26/EOS (n= 1, 0, 0)
    -8.3 ± 99999
    99999 ± 99999
    99999 ± 99999
        GLB: Baseline (n= 2, 3, 2)
    57.5 ± 38.89
    0 ± 0
    40 ± 34.64
        GLB: Change at Week 22 (n= 2, 2, 2)
    -15 ± 21.21
    0 ± 0
    0 ± 42.43
        GLB: Change at Week 26/EOS (n= 1, 0, 0)
    0 ± 99999
    99999 ± 99999
    99999 ± 99999
        GA: Baseline (n= 2, 3, 2)
    62.5 ± 17.678
    35.85 ± 1.202
    55 ± 15
        GA: Change at Week 22 (n= 2, 2, 2)
    -22.5 ± 10.607
    -1.65 ± 16.476
    -2.5 ± 22.345
        GA: Change at Week 26/EOS (n= 1, 0, 0)
    -16.7 ± 99999
    99999 ± 99999
    99999 ± 99999
        GHP: Baseline (n= 2, 3, 2)
    48.9 ± 4.808
    57.95 ± 36.982
    31.8 ± 20.178
        GHP: Change at Week 22 (n= 2, 2, 2)
    -18.2 ± 22.486
    -3.8 ± 11.879
    -5.7 ± 1.556
        GHP: Change at Week 26/EOS (n= 1, 0, 0)
    0 ± 99999
    99999 ± 99999
    99999 ± 99999
        PIE: Baseline (n= 2, 3, 2)
    78.55 ± 30.335
    41.65 ± 23.547
    48.83 ± 33.024
        PIE: Change at Week 22 (n= 2, 2, 2)
    -35.7 ± 25.314
    4.75 ± 3.323
    -3.6 ± 25.314
        PIE: Change at Week 26/EOS (n= 1, 0, 0)
    -17.8 ± 99999
    99999 ± 99999
    99999 ± 99999
        PIT: Baseline (n= 2, 3, 2)
    73.8 ± 37.052
    45.25 ± 63.993
    49.2 ± 26.264
        PIT: Change at Week 22 (n= 2, 2, 2)
    -33.35 ± 6.718
    23.8 ± 20.223
    7.2 ± 23.617
        PIT: Change at Week 26/EOS (n= 1, 0, 0)
    -28.6 ± 99999
    99999 ± 99999
    99999 ± 99999
        FC: Baseline (n= 2, 3, 2)
    85 ± 0
    42.5 ± 60.1
    76.7 ± 14.43
        FC: Change at Week 22 (n= 2, 2, 2)
    -12.5 ± 17.68
    -27.5 ± 99999
    -12.5 ± 17.68
        FC: Change at Week 26/EOS (n= 1, 0, 0)
    -25 ± 99999
    99999 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change from Baseline in Quality of life (QoL) using Child Health Questionnaire™ Child Form 87 (CHQ 87) at Week 26 (EOS)

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    End point title
    Change from Baseline in Quality of life (QoL) using Child Health Questionnaire™ Child Form 87 (CHQ 87) at Week 26 (EOS)
    End point description
    CHQ-CF87 form was designed to be a self-report for subjects 10 years and older. It consists of 87 questions and contains the same scales as the PF-50, (with the omission of the parental impact scales and there are no psychosocial and physical summary scores derived). ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    0 [9]
    0 [10]
    0 [11]
    Units: units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [9] - Individual subject listings was only reported
    [10] - Individual subject listings was only reported
    [11] - Individual subject listings was only reported
    No statistical analyses for this end point

    Secondary: Change from Baseline in Quality of life (QoL) using Children’s Sleep Habits Rating Scale at Week 22 and Week 26 (EOS)

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    End point title
    Change from Baseline in Quality of life (QoL) using Children’s Sleep Habits Rating Scale at Week 22 and Week 26 (EOS)
    End point description
    Children’s sleep habits rating scale consisting of 35 items that yield a Total Sleep Disturbance score (TSDS), as well as eight subscale scores (Bedtime Resistance (BR), Sleep Duration (SD), Parasomnias (P), Sleep Disordered Breathing (SDB), Night Waking (NW), Daytime Sleepiness (DS), Sleep Anxiety (SA), and Sleep Onset Delay (SOD)). The questionnaire was designed for children aged 4 through 12 years. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. 99999 signifies standard deviation not reported as there was only 1 evaluable subject.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22, Week 26/EOS
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: units on a scale
    arithmetic mean (standard deviation)
        BR: Baseline (n= 4, 4, 4)
    8.8 ± 1.89
    11.5 ± 4.65
    7.3 ± 2.5
        BR: Change at Week 22 (n= 4, 4, 4)
    -1.3 ± 1.89
    -0.8 ± 0.96
    1.3 ± 0.96
        BR: Change at Week 26/EOS (n= 3, 2, 2)
    -1 ± 1
    0 ± 0
    1 ± 1.41
        SOD: Baseline (n= 4, 4, 4)
    1.5 ± 1
    2.3 ± 0.96
    1.8 ± 0.96
        SOD: Change at Week 22 (n= 4, 4, 4)
    0 ± 0.82
    0 ± 0.82
    0 ± 0.82
        SOD: Change at Week 26/EOS (n= 3, 2, 2)
    -0.3 ± 0.58
    0 ± 1.41
    -0.5 ± 0.71
        SD: Baseline (n= 4, 4, 4)
    5.3 ± 2.22
    6 ± 2.16
    6.5 ± 2.65
        SD: Change at Week 22 (n= 4, 4, 4)
    -0.8 ± 2.99
    1.3 ± 1.5
    -0.5 ± 1.29
        SD: Change at Week 26/EOS (n= 3, 2, 2)
    -1.7 ± 2.89
    1 ± 1.41
    -1 ± 1.41
        SA: Baseline (n= 4, 4, 4)
    7 ± 1.15
    8.3 ± 3.3
    6 ± 1.41
        SA: Change at Week 22 (n= 4, 4, 3)
    -1.5 ± 1.91
    -0.3 ± 0.58
    0.8 ± 1.71
        SA: Change at Week 26/EOS (n= 3, 2, 2)
    -0.7 ± 1.15
    -0.5 ± 0.71
    0 ± 1.41
        NW: Baseline (n= 4, 4, 4)
    4.3 ± 1.5
    5.8 ± 2.5
    5.5 ± 1.91
        NW: Change at Week 22 (n= 4, 4, 4)
    -0.3 ± 2.06
    -0.5 ± 0.58
    0 ± 1.63
        NW: Change at Week 26/EOS (n= 3, 2, 2)
    -1 ± 1.73
    0 ± 0
    -0.5 ± 0.71
        P: Baseline (n= 2, 4, 4)
    8.5 ± 0.71
    12 ± 2.94
    10 ± 2.31
        P: Change at Week 22 (n= 2, 4, 4)
    -1 ± 0
    -0.3 ± 2.87
    0.3 ± 3.4
        P: Change at Week 26/EOS (n= 1, 2, 2)
    -1 ± 99999
    -0.5 ± 0.71
    -1 ± 0
        SDB: Baseline (n= 4, 4, 4)
    3.3 ± 0.5
    5.8 ± 3.2
    4.3 ± 0.5
        SDB: Change at Week 22 (n= 4, 4, 3)
    0.8 ± 0.96
    -1.7 ± 2.89
    0.5 ± 1.73
        SDB: Change at Week 26/EOS(n= 3, 2, 2)
    0.7 ± 1.15
    0 ± 0
    -0.5 ± 0.71
        DS: Baseline (n= 4, 4, 4)
    9.5 ± 1.29
    11.3 ± 3.4
    11.5 ± 3.87
        DS: Change at Week 22 (n= 4, 4, 4)
    -0.3 ± 0.5
    0.5 ± 2.65
    0.5 ± 0.58
        DS: Change at Week 26/EOS (n= 3, 2, 2)
    0.7 ± 1.15
    1 ± 1.41
    1 ± 0
        TSDS: Baseline (n= 2, 4, 4)
    42.5 ± 2.12
    58.8 ± 16.82
    50.3 ± 12.28
        TSDS: Change at Week 22 (n= 2, 4, 2)
    1.5 ± 4.95
    2 ± 5.66
    2 ± 5.83
        TSDS: Change at Week 26/EOS (n= 1, 2, 2)
    -2 ± 99999
    1 ± 2.83
    -2 ± 4.24
    No statistical analyses for this end point

    Secondary: Change from Baseline in Concentration of Recombinant Human Heparan N-Sulfatase (rhHNS) in Cerebrospinal Fluid (CSF) at Week 22

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    End point title
    Change from Baseline in Concentration of Recombinant Human Heparan N-Sulfatase (rhHNS) in Cerebrospinal Fluid (CSF) at Week 22
    End point description
    Cerebrospinal fluid samples were collected from subjects through an implanted IDDD or via lumbar puncture (LP) immediately prior to each administration of HGT-1410. There was no evidence of accumulation of HGT-1410 in the CSF over the duration of the study. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    0 [12]
    0 [13]
    0 [14]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [12] - There was no evidence of accumulation of HGT-1410 in the CSF over the duration of the study.
    [13] - There was no evidence of accumulation of HGT-1410 in the CSF over the duration of the study.
    [14] - There was no evidence of accumulation of HGT-1410 in the CSF over the duration of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Concentration of Heparan Sulfate and Heparan Sulfate derivatives in Cerebrospinal Fluid (CSF) at Week 6, 10, 14, 18, 22 and 26(EOS)

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    End point title
    Change from Baseline in Concentration of Heparan Sulfate and Heparan Sulfate derivatives in Cerebrospinal Fluid (CSF) at Week 6, 10, 14, 18, 22 and 26(EOS)
    End point description
    Levels of heparan sulfate and its derivatives were evaluated using the proprietary Sensi-Pro (SP) high-performance liquid chromatography (HPLC) based assay. Here, n = subjects evaluable for specified category for each arm, respectively. ITT population. Abbreviation: SP Total Heparan Sulfate (SPTHS), SP Non-Reducing End Assay (SPNREA)
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6, 10, 14, 18, 22 and 26(EOS)
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: picomole per milliliter (pmol/mL)
    arithmetic mean (standard deviation)
        SPTHS: Baseline (n= 4, 4, 4)
    90570.5 ± 38088.67
    83287 ± 26012.16
    69049.7 ± 42659.28
        SPTHS: Change at Week 6 (n= 4, 2, 2)
    -34167.7 ± 20439.34
    -65862.6 ± 23010.52
    -41331.4 ± 38967.66
        SPTHS: Week 10 (n= 4, 4, 3)
    -41825.4 ± 13482.5
    -54343.7 ± 25891.78
    -39441.8 ± 29771.14
        SPTHS: Change at Week 14 (n= 4, 3, 3)
    -40309 ± 15107.94
    -64763.9 ± 25285.97
    -32249.2 ± 21862.89
        SPTHS: Change at Week 22 (n= 4, 4, 4)
    -35469.5 ± 20922.54
    -60931.7 ± 20699.36
    -44669.5 ± 38360.07
        SPNREA: Baseline (n= 4, 4, 4)
    1255.93 ± 471.403
    1487.67 ± 329.79
    1198.34 ± 627.436
        SPNREA: Change at Week 6 (n= 4, 2, 2)
    -213.25 ± 330.836
    -1022.53 ± 163.905
    -677.79 ± 393.281
        SPNREA: Change at Week 10 (n= 4, 4, 3)
    -411.77 ± 268.961
    -788.65 ± 390.761
    -533.38 ± 476.259
        SPNREA: Change at Week 14 (n= 4, 3, 3)
    -359.15 ± 272.695
    -1033.58 ± 371.566
    -491.24 ± 177.701
        SPNREA: Change at Week 22 (n= 4, 4, 4)
    254.07 ± 333.649
    -877.84 ± 435.044
    -686.13 ± 517.558
    No statistical analyses for this end point

    Secondary: Change from Baseline in Brain Magnetic Resonance Imaging (MRI) at Week 22

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    End point title
    Change from Baseline in Brain Magnetic Resonance Imaging (MRI) at Week 22
    End point description
    Brain MRI was measured for grey matter volume (GMV), white matter volume (WMV) and intracranial cerebro spinal fluid (CSF) Volume [ICSFV] (Ventricles + Additional CSF Space). ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: milliliter (mL)
    arithmetic mean (standard deviation)
        GMV: Baseline
    550.5 ± 111.043
    600.28 ± 67.884
    534.25 ± 117.291
        GMV: Change at Week 22
    -42.84 ± 36.793
    -32.87 ± 36.862
    -33.7 ± 24.161
        WMV: Baseline
    403.72 ± 105.575
    442.45 ± 79.814
    348.28 ± 76.854
        WMV: Change at Week 22
    -2.86 ± 13.997
    -0.44 ± 9.793
    3.33 ± 11.419
        ICSFV: Baseline
    26.152 ± 9.2975
    20.925 ± 15.9681
    22.904 ± 20.8459
        ICSFV: Change at Week 22
    4.739 ± 4.6455
    7.375 ± 6.6573
    2.886 ± 3.9153
    No statistical analyses for this end point

    Secondary: Change from Baseline in Mean Auditory Brainstem Response (ABR) at Week 22

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    End point title
    Change from Baseline in Mean Auditory Brainstem Response (ABR) at Week 22
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Mean ABR air and bone conduction threshold were assessed. Mean ABR bone conduction threshold was not possible to be reported as there was insufficient data to be analysed. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. 99999 signifies standard deviation not reported as there was only 1 evaluable subject.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: Decibel Above Normal Adult Hearing Level
    arithmetic mean (standard deviation)
        Right Ear: Baseline (n= 1, 2, 3)
    62.5 ± 99999
    49.17 ± 14.216
    56.25 ± 8.839
        Right Ear: Change at Week 22 (n= 1, 2, 3)
    -10 ± 99999
    -0.83 ± 22.407
    -3.75 ± 15.91
        Left Ear: Baseline (n= 2, 2, 4)
    52.5 ± 10.607
    44.38 ± 24.696
    55 ± 7.071
        Left Ear: Change at Week 22 (n= 2, 2, 4)
    5 ± 7.071
    3.13 ± 10.68
    -5 ± 14.142
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Latencies

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Latencies
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. The Inter-peak Latencies (IPL) were calculated by subtracting the absolute latencies (AL). The Inter-aural Latencies (IAL) were calculated by subtracting the absolute wave V latencies of the right and left ear. IAL, IPL and AL were reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. Abbreviation: Right Ear (RE), Left Ear (LE), Wave (W)
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: millisecond (ms)
    arithmetic mean (standard deviation)
        RE,IPL I-III: Baseline (n= 3, 3, 3)
    2.29 ± 0.257
    2.33 ± 0.193
    2.53 ± 0.153
        RE,IPL I-III: Change at Week 22 (n= 3, 3, 2)
    -0.09 ± 0.147
    0.07 ± 0.014
    -0.11 ± 0.183
        RE,IPL III-V: Baseline (n= 3, 3, 3)
    2.04 ± 0.24
    1.96 ± 0.119
    2.17 ± 0.261
        RE,IPL III-V: Change at Week 22 (n= 3, 3, 2)
    -0.08 ± 0.185
    0.06 ± 0.085
    -0.06 ± 0.304
        RE,IPL I-V: Baseline (n= 3, 3, 3)
    4.34 ± 0.047
    4.29 ± 0.238
    4.71 ± 0.352
        RE,IPL I-V: Change at Week 22 (n= 3, 3, 3)
    -0.17 ± 0.269
    0.2 ± 0.131
    -0.17 ± 0.187
        LE,IPL I-III: Baseline (n= 3, 3, 4)
    2.32 ± 0.206
    2.4 ± 0.303
    2.53 ± 0.153
        LE,IPL I-III: Change at Week 22 (n= 3, 3, 3)
    -0.01 ± 0.129
    0.11 ± 0.219
    -0.24 ± 0.065
        LE,IPL III-V: Baseline (n= 3, 3, 4)
    2.06 ± 0.255
    2.09 ± 0.311
    2.15 ± 0.225
        LE,IPL III-V: Change at Week 22 (n= 3, 3, 3)
    -0.02 ± 0.075
    0.06 ± 0.04
    0.09 ± 0.091
        LE,IPL I-V: Baseline (n= 3, 3, 4)
    4.39 ± 0.264
    4.48 ± 0.394
    4.68 ± 0.33
        LE,IPL I-V: Week 22 (n= 3, 3, 3)
    -0.03 ± 0.185
    0.17 ± 0.191
    -0.15 ± 0.07
        IAL: Baseline (n= 3, 3, 3)
    -0.05 ± 0.061
    0.07 ± 0.081
    -0.07 ± 0.058
        IAL: Change at Week 22 (n= 3, 3, 3)
    0.04 ± 0.301
    0.46 ± 0.849
    0.28 ± 0.312
        AL-RE,WI: Baseline (n= 3, 3, 3)
    1.73 ± 0.237
    1.76 ± 0.012
    1.59 ± 0.156
        AL-RE,WI: Change at Week 22 (n= 3, 3, 3)
    0 ± 0.466
    0.47 ± 0.987
    0.46 ± 0.54
        AL-RE,WIII: Baseline (n= 3, 3, 3)
    4.02 ± 0.45
    4.09 ± 0.181
    4.12 ± 0.197
        AL-RE,WIII: Change at Week 22 (n= 3, 3, 2)
    -0.09 ± 0.355
    -0.03 ± 0.042
    0.35 ± 0.687
        AL-RE,WV: Baseline (n= 3, 3, 3)
    6.06 ± 0.283
    6.06 ± 0.227
    6.3 ± 0.454
        AL-RE,WV: Change at Week 22 (n= 3, 3, 3)
    -0.17 ± 0.478
    0.67 ± 1.109
    0.29 ± 0.633
        AL-LE,WI: Baseline (n= 3, 3, 4)
    1.73 ± 0.13
    1.78 ± 0.233
    1.68 ± 0.144
        AL-LE,WI: Change at Week 22 (n= 3, 3, 3)
    -0.18 ± 0.111
    0.04 ± 0.16
    0.16 ± 0.33
        AL-LE,WIII: Baseline (n= 3, 3, 4)
    4.05 ± 0.323
    4.18 ± 0.504
    4.22 ± 0.189
        AL-LE,WIII: Change at Week 22 (n= 3, 3, 3)
    -0.19 ± 0.165
    0.15 ± 0.306
    -0.08 ± 0.266
        AL-LE,WV: Baseline (n= 3, 3, 4)
    6.12 ± 0.278
    6.26 ± 0.612
    6.36 ± 0.412
        AL-LE,WV: Change at Week 22 (n= 3, 3, 4)
    -0.21 ± 0.178
    0.24 ± 0.227
    0.01 ± 0.324
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Amplitudes

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Amplitudes
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR amplitudes by left ear (LE) and right ear (RE) were reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: microvolt (mcV)
    arithmetic mean (standard deviation)
        RE, Wave I: Baseline (n= 2, 3, 3)
    0.49 ± 0.042
    0.26 ± 0.097
    0.42 ± 0.118
        RE, Wave I: Change at Week 22 (n= 2, 3, 3)
    -0.23 ± 0.042
    -0.03 ± 0.216
    -0.17 ± 0.147
        RE, Wave III: Baseline (n= 2, 3, 3)
    0.33 ± 0.156
    0.24 ± 0.113
    0.35 ± 0.195
        RE, Wave III: Change at Week 22 (n= 2, 3, 2)
    -0.05 ± 0.099
    -0.16 ± 0.156
    -0.12 ± 0.117
        RE, Wave V: Baseline (n= 2, 3, 3)
    0.64 ± 0.403
    0.32 ± 0.101
    0.47 ± 0.144
        RE, Wave V: Change at Week 22 (n= 2, 3, 3)
    -0.28 ± 0.354
    -0.14 ± 0.201
    -0.09 ± 0.145
        LE, Wave I: Baseline (n= 2, 3, 4)
    0.4 ± 0.028
    0.26 ± 0.133
    0.44 ± 0.199
        LE, Wave I: Change at Week 22 (n= 2, 3, 3)
    -0.1 ± 0.17
    -0.01 ± 0.135
    0.02 ± 0.221
        LE, Wave III: Baseline (n= 2, 3, 4)
    0.22 ± 0.106
    0.21 ± 0.102
    0.38 ± 0.194
        LE, Wave III: Change at Week 22 (n= 2, 3, 3)
    0.05 ± 0.057
    0.02 ± 0.047
    -0.09 ± 0.188
        LE, Wave V: Baseline (n= 2, 3, 4)
    0.52 ± 0.269
    0.29 ± 0.17
    0.48 ± 0.123
        LE, Wave V: Change at Week 22 (n= 2, 3, 4)
    -0.13 ± 0.24
    -0.01 ± 0.085
    -0.02 ± 0.134
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Amplitude Ratio

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Amplitude Ratio
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR amplitudes(A), log-transformed amplitudes (LTA), square-root transformed amplitudes (STA) by left ear (LE) and right ear (RE) wave V/I in ratio was reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively. 99999 signifies standard deviation not reported as there was only 1 evaluable subject and data was not available for the specific measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: ratio
    arithmetic mean (standard deviation)
        A-RE, Wave V/I: Baseline (n= 2, 2, 2)
    1.34 ± 0.94
    1.83 ± 0.403
    1.09 ± 0.057
        A-RE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.14 ± 0.269
    -1.48 ± 99999
    0.42 ± 99999
        A-LE, Wave V/I: Baseline (n= 2, 2, 2)
    1.33 ± 0.764
    2.43 ± 2.341
    1.26 ± 0.014
        A-LE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.37 ± 0.453
    -0.15 ± 99999
    0.28 ± 99999
        LTA-RE, Wave V/I: Baseline (n= 2, 2, 2)
    0.146 ± 0.7733
    0.589 ± 0.2227
    0.086 ± 0.0519
        LTA-RE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.188 ± 0.3011
    -3.245 ± 99999
    0.336 ± 99999
        LTA-LE, Wave V/I: Baseline (n= 2, 2, 2)
    0.195 ± 0.6093
    0.572 ± 1.1791
    0.231 ± 0.0112
        LTA-LE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.188 ± 0.1787
    -0.217 ± 99999
    0.202 ± 99999
        STA-RE, Wave V/I: Baseline (n= 2, 2, 2)
    1.116 ± 0.4212
    1.347 ± 0.1496
    1.044 ± 0.0271
        STA-RE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.082 ± 0.1409
    -0.996 ± 99999
    0.188 ± 99999
        STA-LE, Wave V/I: Baseline (n= 2, 2, 2)
    1.128 ± 0.3385
    1.449 ± 0.8078
    1.122 ± 0.0063
        STA-LE, Wave V/I: Change at Week 22 (n= 2, 1, 1)
    0.13 ± 0.1448
    -0.09 ± 99999
    0.119 ± 99999
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Log Tranformed Latencies

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Log Tranformed Latencies
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR log-transformed latencies (LTL) by left and right ear were reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: log tranformed (latency [ms])
    arithmetic mean (standard deviation)
        LTL-RE, Wave I: Baseline (n= 3, 3, 3)
    0.54 ± 0.1326
    0.567 ± 0.0066
    0.461 ± 0.0956
        LTL-RE, Wave I: Change at Week 22 (n= 3, 3, 3)
    -0.006 ± 0.2585
    0.179 ± 0.4104
    0.242 ± 0.2791
        LTL-RE, Wave III: Baseline (n= 3, 3, 3)
    1.387 ± 0.1121
    1.409 ± 0.0439
    1.416 ± 0.0483
        LTL-RE, Wave III: Change at Week 22 (n= 3, 3, 2)
    -0.019 ± 0.0882
    -0.008 ± 0.0108
    0.074 ± 0.148
        LTL-RE, Wave V: Baseline (n= 3, 3, 3)
    1.802 ± 0.0461
    1.801 ± 0.0374
    1.838 ± 0.0731
        LTL-RE, Wave V: Change at Week 22 (n= 3, 3, 3)
    -0.028 ± 0.0794
    0.093 ± 0.1529
    0.044 ± 0.0963
        LTL-LE, Wave I: Baseline (n= 3, 3, 4)
    0.546 ± 0.0769
    0.57 ± 0.1268
    0.518 ± 0.0838
        LTL-LE, Wave I: Change at Week 22 (n= 3, 3, 3)
    -0.106 ± 0.0653
    0.019 ± 0.0927
    0.088 ± 0.1812
        LTL-LE, Wave III: Baseline (n= 3, 3, 4)
    1.397 ± 0.0804
    1.424 ± 0.1213
    1.438 ± 0.0455
        LTL-LE, Wave III: Change at Week 22 (n= 3, 3, 3)
    -0.046 ± 0.0394
    0.032 ± 0.0657
    -0.02 ± 0.0624
        LTL-LE, Wave V: Baseline (n= 3, 3, 4)
    1.81 ± 0.045
    1.831 ± 0.0955
    1.849 ± 0.0658
        LTL-LE, Wave V: Change at Week 22 (n= 3, 3, 4)
    -0.034 ± 0.0281
    0.036 ± 0.0338
    0.002 ± 0.0494
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Log Tranformed Amplitude

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Log Tranformed Amplitude
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR log-transformed amplitudes (LTA) by left and right ear were reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: log transformed (amplitude [mcV])
    arithmetic mean (standard deviation)
        LTA-RE, Wave I: Baseline (n= 2, 3, 3)
    -0.715 ± 0.0867
    -1.379 ± 0.3627
    -0.893 ± 0.2741
        LTA-RE, Wave I: Change at Week 22 (n= 2, 3, 3)
    -0.659 ± 0.2456
    -0.24 ± 1.018
    -0.76 ± 0.8475
        LTA-RE, Wave III: Baseline (n= 2, 3, 3)
    -1.168 ± 0.4901
    -1.527 ± 0.589
    -1.17 ± 0.6224
        LTA-RE, Wave III: Change at Week 22 (n= 2, 3, 2)
    -0.116 ± 0.2867
    -1.239 ± 1.5038
    -0.549 ± 0.4627
        LTA-RE, Wave V: Baseline (n= 2, 3, 3)
    -0.567 ± 0.6834
    -1.19 ± 0.3631
    -0.792 ± 0.2929
        LTA-RE, Wave V: Change at Week 22 (n= 2, 3, 3)
    -0.474 ± 0.5435
    -1.237 ± 1.5458
    -0.214 ± 0.3107
        LTA-LE, Wave I: Baseline (n= 2, 3, 4)
    -0.918 ± 0.0708
    -1.445 ± 0.5468
    -0.875 ± 0.4212
        LTA-LE, Wave I: Change at Week 22 (n= 2, 3, 3)
    -0.409 ± 0.6445
    0.078 ± 0.5695
    -0.268 ± 0.8163
        LTA-LE, Wave III: Baseline (n= 2, 3, 4)
    -1.602 ± 0.5149
    -1.643 ± 0.5086
    -1.057 ± 0.4761
        LTA-LE, Wave III: Change at Week 22 (n= 2, 3, 3)
    0.265 ± 0.3271
    0.053 ± 0.151
    -0.374 ± 0.7773
        LTA-LE, Wave V: Baseline (n= 2, 3, 4)
    -0.726 ± 0.5418
    -1.372 ± 0.5377
    -0.748 ± 0.2486
        LTA-LE, Wave V: Change at Week 22 (n= 2, 3, 4)
    -0.217 ± 0.4692
    0.006 ± 0.3379
    -0.066 ± 0.2771
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Tranformed Latencies

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Tranformed Latencies
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR square-root log-transformed latency (STL) by left and right ear were reported. ITT population.Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: square-root transformed (latency [ms])
    arithmetic mean (standard deviation)
        STL-RE, Wave I: Baseline (n= 3, 3, 3)
    1.312 ± 0.0886
    1.328 ± 0.0044
    1.26 ± 0.061
        STL-RE, Wave I: Change at Week 22 (n= 3, 3, 3)
    -0.002 ± 0.1734
    0.145 ± 0.3167
    0.166 ± 0.1935
        STL-RE, Wave III: Baseline (n= 3, 3, 3)
    2.003 ± 0.1123
    2.023 ± 0.0446
    2.03 ± 0.0487
        STL-RE, Wave III:Change at Week 22 (n= 3, 3, 2)
    -0.021 ± 0.0884
    -0.008 ± 0.0107
    0.08 ± 0.1593
        STL-RE, Wave V: Baseline (n= 3, 3, 3)
    2.462 ± 0.0571
    2.461 ± 0.0461
    2.508 ± 0.091
        STL-RE, Wave V: Change at Week 22 (n= 3, 3, 3)
    -0.035 ± 0.0974
    0.125 ± 0.2057
    0.056 ± 0.1233
        STL-LE, Wave I: Baseline (n= 3, 3, 4)
    1.315 ± 0.05
    1.332 ± 0.0858
    1.297 ± 0.055
        STL-LE, Wave I: Change at Week 22 (n= 3, 3, 3)
    -0.068 ± 0.0425
    0.014 ± 0.0608
    0.059 ± 0.1223
        STL-LE, Wave III: Baseline (n= 3, 3, 4)
    2.012 ± 0.0805
    2.04 ± 0.1236
    2.053 ± 0.0464
        STL-LE, Wave III: Change at Week 22 (n= 3, 3, 3)
    -0.047 ± 0.0403
    0.035 ± 0.0709
    -0.019 ± 0.0644
        STL-LE, Wave V: Baseline (n= 3, 3, 4)
    2.473 ± 0.0559
    2.5 ± 0.1208
    2.522 ± 0.0824
        STL-LE, Wave V: Change at Week 22 (n= 3, 3, 4)
    -0.042 ± 0.0354
    0.047 ± 0.0438
    0.002 ± 0.0633
    No statistical analyses for this end point

    Secondary: Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Tranformed Amplitude

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    End point title
    Change from Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Tranformed Amplitude
    End point description
    ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR square-root transformed amplitude (STA) by left and right ear were reported. ITT population. Here, n = subjects evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 22
    End point values
    HGT-1410 10 mg HGT-1410 90 mg HGT-1410 45 mg
    Number of subjects analysed
    4
    4
    4
    Units: square-root transformed(amplitude [mcV])
    arithmetic mean (standard deviation)
        STA-RE, Wave I: Baseline (n= 2, 3, 3)
    0.7 ± 0.0303
    0.507 ± 0.0933
    0.644 ± 0.0896
        STA-RE, Wave I: Change at Week 22 (n= 2, 3, 3)
    -0.193 ± 0.0535
    -0.044 ± 0.2298
    -0.172 ± 0.1615
        STA-RE, Wave III: Baseline (n= 2, 3, 3)
    0.566 ± 0.1374
    0.479 ± 0.1274
    0.575 ± 0.171
        STA-RE, Wave III: Change at Week 22 (n= 2, 3, 2)
    -0.038 ± 0.0838
    -0.211 ± 0.2317
    -0.122 ± 0.0927
        STA-RE, Wave V: Baseline (n= 2, 3, 3)
    0.775 ± 0.2599
    0.557 ± 0.0954
    0.678 ± 0.1022
        STA-RE, Wave V: Change at Week 22 (n= 2, 3, 3)
    -0.18 ± 0.2183
    -0.197 ± 0.2547
    -0.069 ± 0.1049
        STA-LE, Wave I: Baseline (n= 2, 3, 4)
    0.632 ± 0.0224
    0.499 ± 0.133
    0.655 ± 0.1437
        STA-LE, Wave I: Change at Week 22 (n= 2, 3, 3)
    0.101 ± 0.1638
    0.006 ± 0.1365
    -0.028 ± 0.1961
        STA-LE, Wave III: Baseline (n= 2, 3, 4)
    0.456 ± 0.1162
    0.45 ± 0.1131
    0.601 ± 0.1508
        STA-LE, Wave III: Change at Week 22 (n= 2, 3, 3)
    0.057 ± 0.068
    0.015 ± 0.0422
    -0.085 ± 0.1798
        STA-LE, Wave V: Baseline (n= 2, 3, 4)
    0.709 ± 0.1896
    0.518 ± 0.1488
    0.692 ± 0.0873
        STA-LE, Wave V: Change at Week 22 (n= 2, 3, 4)
    -0.084 ± 0.167
    -0.004 ± 0.0832
    -0.019 ± 0.0956
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline to Week 30 (follow-up)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    10 mg rhHNS
    Reporting group description
    10 mg monthly via an IDDD (every 28 [+/-7 days]) for a total of 6 months Recombinant human heparan N-sulfatase (rhHNS)

    Reporting group title
    90 mg rhHNS
    Reporting group description
    90 mg monthly via an IDDD (every 28 [+/-7 days]) for a total of 6 months Recombinant human heparan N-sulfatase (rhHNS)

    Reporting group title
    45 mg rhHNS
    Reporting group description
    45 mg monthly via an IDDD (every 28 [+/-7 days]) for a total of 6 months Recombinant human heparan N-sulfatase (rhHNS)

    Serious adverse events
    10 mg rhHNS 90 mg rhHNS 45 mg rhHNS
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 4 (25.00%)
    3 / 4 (75.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Surgical and medical procedures
    Medical device change
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Device breakage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device component issue
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Postoperative wound infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    10 mg rhHNS 90 mg rhHNS 45 mg rhHNS
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Pallor
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Infection prophylaxis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Administration site pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Device breakage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Device failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Catheter site erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    Implant site swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Malaise
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    Medical device complication
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Irritability
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 4 (25.00%)
    2 / 4 (50.00%)
         occurrences all number
    5
    2
    7
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Depressed mood
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Restlessness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Penile adhesion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Labia enlarged
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Open wound
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Post procedural discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Procedural site reaction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Procedural vomiting
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Csf white blood cell count increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    Csf protein increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Norovirus test positive
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Serum ferritin decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    2
    Nervous system disorders
    Cauda equina syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    6
    0
    Crying
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Cognitive disorder
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Drooling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    4
    10
    0
    Dizziness
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Motor dysfunction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Memory impairment
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 4 (50.00%)
         occurrences all number
    0
    0
    2
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    Tympanic membrane disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Abnormal faeces
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 4 (50.00%)
         occurrences all number
    5
    0
    3
    Constipation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Regurgitation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
         occurrences all number
    6
    2
    1
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    6
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Trigger finger
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Candida nappy rash
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    Otitis media
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Post procedural infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Proteus infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    2 / 4 (50.00%)
         occurrences all number
    3
    2
    4
    Postoperative wound infection
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
         occurrences all number
    2
    2
    1
    Viral rash
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Jan 2010
    Clarified that the study’s primary investigation is focused on the safety and tolerability of the investigation drug, HGT-1410. This clarification was achieved through the modification of the primary objective and primary endpoint with the removal of language stating the safety, tolerability, and patency of the IDDD will be an objective and endpoint of the study. In addition, the need to draw a blood sample of PK analysis on Day 1 of the IT dosing week. As PK blood samples are drawn only prior to or following HGT-1410 IT injection.
    25 Feb 2010
    Clarified the Shire HGT safety review and communication process before the enrollment and implantation of an IDDD in a new subject.
    14 May 2010
    Clarified the IDDD replacement timeframe (if the failure of device is confirmed [defined as two successive months of non-operation); to update safety information on IT drug delivery via lumbar puncture; to shorten both the required time a subject must stay after study drug treatment and the PK sampling time points to 3 days (formerly 7 days) to be less onerous on the subject and family. In addition, the inclusion criterion requiring confirmation of MPS IIIA allowed the subject to have a documented mutations for MPS IIIA were added as alternative criterion for the diagnosis of MPS IIIA in screened subjects, since this type of testing has been found to be fairly common in subjects with MPS IIIA.
    13 Dec 2010
    Incorporated: a change in Medical Monitor, a reduction in the amount of time a subject would be required to remain at a study center, a harmonization and clarification of the study stopping rules as they relate to study drug dose escalation and data monitoring committee (DMC) review, and the addition of a requirement of pregnancy testing for female subjects who have reached menarche.
    14 Jul 2011
    Changed Cohort 3’s dose and dosing schedule. Additionally, the protocol was amended to align the protocol study processes with the processes followed at the study site, in particular: subjects may miss the Day 1 visit if a subject meets specific criteria, and ABR and MRI may be performed under the same anesthesia as that of the IDDD implantation. In addition, the text regarding the management of IDDD-related issues was simplified in the protocol, with the management details specified in a new protocol Appendix 5.
    28 Sep 2011
    Stipulated the total number of times that a subject may have an IDDD revision (partial or complete replacement) during the course of the trial was 2, and the total number of times a subject may have an X-ray was limited to 6. It was also specified that in the event that the IDDD failed again after the 2 permissible revisions that HGT-1410 may have been administered and CSF collected by lumbar puncture for the remainder of the subject's participation in the study. Additionally, the ABR language was modified for clarity and it was specifically stated that all subjects were to undergo ABR testing.

    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.
    Comparison to values obtained in a longitudinal, 12 month, natural history study of untreated subjects with MPS IIIA was not reported as it was to be compared with another study protocol HGT-SAN-053
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