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    Clinical Trial Results:
    A Phase 3, randomized, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of UX007 in the treatment of movement disorders associated with Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

    Summary
    EudraCT number
    2015-005536-17
    Trial protocol
    DE   ES   FR   GB   IT  
    Global end of trial date
    09 Oct 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Apr 2020
    First version publication date
    24 Apr 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    UX007G-CL301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02960217
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    EMA/190573: Unique Product Identifier (UPI)
    Sponsors
    Sponsor organisation name
    Ultragenyx Pharmaceutical Inc.
    Sponsor organisation address
    60 Leveroni Court, Novato, United States, California 94949
    Public contact
    Medical Information, Ultragenyx Pharmaceutical Inc, +1 888- 756-8657, medinfo@ultragenyx.com
    Scientific contact
    Medical Information, Ultragenyx Pharmaceutical Inc, +1 888- 756-8657, medinfo@ultragenyx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Oct 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Oct 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Primary Objectives: •Evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS
    Protection of trial subjects
    The trial was designed, conducted, recorded, and reported in accordance with the principles established by the 18th World Medical Association General Assembly (Helsinki, 1964) and subsequent amendments and clarifications adopted by the General Assemblies. The investigators made every effort to ensure that the study was conducted in full conformance with Helsinki principles, international Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines, current Food and Drug Administration (FDA) regulations, EU Clinical Trial Directive 2001/20/EC, and local ethical and regulatory requirements. Each investigator was thoroughly familiar with the appropriate administration and potential risks of administration of the study drug, as described in the protocol and Investigator’s Brochure, prior to the initiation of the study. The method of obtaining and documenting informed consent and the contents of the informed consent form (ICF) complied with ICH GCP guidelines, the requirements of 21 CFR Part 50, “Protection of Human Subjects,” the Health Insurance Portability and Accountability Act regulations, and all other applicable regulatory requirements. Investigators were responsible for preparing the ICF and submitting it to the Sponsor for approval prior to submission to the Institutional Review Board (IRB). All ICFs were written in regional language and contained the minimum elements for consent as mandated by the ICH guidelines. An IRB-approved ICF was provided by the Sponsor prior to initiation of the study. Investigators obtained signed written informed consent from each potential study subject prior to the conduct of any study procedures and after the methods, objectives, requirements, and potential risks of the study were fully explained to each potential subject. Consent for participation could be withdrawn at any time for any reason by the subject.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Apr 2017
    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
    France: 8
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 15
    Country: Number of subjects enrolled
    Italy: 5
    Worldwide total number of subjects
    44
    EEA total number of subjects
    29
    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)
    9
    Adults (18-64 years)
    28
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    During a 6-week Run-in Period, subjects recorded disabling paroxysmal movement disorder events in a daily electronic Glut1 DS movement disorder diary.

    Pre-assignment period milestones
    Number of subjects started
    44
    Number of subjects completed
    43

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Randomized not treated: 1
    Period 1
    Period 1 title
    Maintenance Phase: Treatment Period 1
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor
    Blinding implementation details
    Double-blind conditions were established during this period so that neither the sponsor, subject, or site personnel involved in study conduct knew the identity of a subject’s treatment. After all subjects completed the double-blind period, unblinding of the study occurred.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-Blind UX007 Followed by Placebo
    Arm description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    triheptanoin
    Investigational medicinal product code
    UX007
    Other name
    C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Arm title
    Double-Blind Placebo Followed by UX007
    Arm description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    safflower oil
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Number of subjects in period 1 [1]
    Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007
    Started
    22
    21
    Completed
    21
    21
    Not completed
    1
    0
         Adverse event
    1
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One subject was randomized but did not receive any treatment due to a protocol violation; this subject was not included in any analyses in this study.
    Period 2
    Period 2 title
    Maintenance Phase: Crossover Washout
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-Blind UX007 Followed by Placebo
    Arm description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Double-Blind Placebo Followed by UX007
    Arm description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007
    Started
    21
    21
    Completed
    21
    21
    Period 3
    Period 3 title
    Maintenance Phase: Treatment Period 2
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor
    Blinding implementation details
    Double-blind conditions were established during this period so that neither the sponsor, subject, or site personnel involved in study conduct knew the identity of a subject’s treatment. After all subjects completed the double-blind period, unblinding of the study occurred.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-Blind UX007 Followed by Placebo
    Arm description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    safflower oil
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Arm title
    Double-Blind Placebo Followed by UX007
    Arm description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    triheptanoin
    Investigational medicinal product code
    UX007
    Other name
    C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Number of subjects in period 3
    Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007
    Started
    21
    21
    Completed
    20
    18
    Not completed
    1
    3
         Other, not specified
    -
    1
         Adverse event
    -
    1
         Lack of efficacy
    1
    -
         Consent withdrawn by subject
    -
    1
    Period 4
    Period 4 title
    Open-Label Extension Phase
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-Blind UX007 Followed by Placebo-->Open Label UX007
    Arm description
    Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.
    Arm type
    Experimental

    Investigational medicinal product name
    triheptanoin
    Investigational medicinal product code
    UX007
    Other name
    C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Arm title
    Double-Blind Placebo Followed by UX007-->Open Label UX007
    Arm description
    Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.
    Arm type
    Experimental

    Investigational medicinal product name
    triheptanoin
    Investigational medicinal product code
    UX007
    Other name
    C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

    Number of subjects in period 4 [2]
    Double-Blind UX007 Followed by Placebo-->Open Label UX007 Double-Blind Placebo Followed by UX007-->Open Label UX007
    Started
    20
    13
    Completed
    0
    0
    Not completed
    20
    13
         Other, not specified
    -
    1
         Adverse event
    1
    -
         Lack of efficacy
    1
    1
         Sponsor decision
    18
    11
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 5 subjects completed the double blind period but did not continue in the open label period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double-Blind UX007 Followed by Placebo
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.

    Reporting group title
    Double-Blind Placebo Followed by UX007
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.

    Reporting group values
    Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007 Total
    Number of subjects
    22 21 43
    Age categorical
    Units: Subjects
        < 18 years old
    7 9 16
        >= 18 years old
    15 12 27
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    23.41 ± 13.156 18.37 ± 5.730 -
    Gender categorical
    Units: Subjects
        Female
    12 12 24
        Male
    10 9 19
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    1 0 1
        Not Hispanic or Latino
    17 17 34
        Unknown or Not Reported
    4 4 8
    Race
    Units: Subjects
        Black or African American
    0 1 1
        White
    18 16 34
        Missing
    4 4 8

    End points

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    End points reporting groups
    Reporting group title
    Double-Blind UX007 Followed by Placebo
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.

    Reporting group title
    Double-Blind Placebo Followed by UX007
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Reporting group title
    Double-Blind UX007 Followed by Placebo
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.

    Reporting group title
    Double-Blind Placebo Followed by UX007
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Reporting group title
    Double-Blind UX007 Followed by Placebo
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks.

    Reporting group title
    Double-Blind Placebo Followed by UX007
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
    Reporting group title
    Double-Blind UX007 Followed by Placebo-->Open Label UX007
    Reporting group description
    Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

    Reporting group title
    Double-Blind Placebo Followed by UX007-->Open Label UX007
    Reporting group description
    Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

    Subject analysis set title
    Full Analysis Set: Double-Blind UX007
    Subject analysis set type
    Full analysis
    Subject analysis set description
    UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Full Analysis Set: all randomized subjects who received at least 1 dose of study drug.

    Subject analysis set title
    Full Analysis Set: Double-Blind Placebo
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Placebo for 10 weeks. Full Analysis Set: all randomized subjects who received at least 1 dose of study drug.

    Subject analysis set title
    Safety Analysis Set: Double-Blind UX007
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Safety Analysis Set: all randomized subjects who received at least 1 dose of study drug.

    Subject analysis set title
    Safety Analysis Set: Double-Blind Placebo
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Placebo for 10 weeks. Safety Analysis Set: all randomized subjects who received at least 1 dose of study drug.

    Subject analysis set title
    Safety Analysis Set: Open-Label UX007
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    UX007 treatment continuation for up to 3 years. Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.

    Primary: Maintenance Phase Movement Disorder Frequency

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    End point title
    Maintenance Phase Movement Disorder Frequency [1]
    End point description
    The frequency of paroxysmal movement disorders captured as disabling movement disorder events (normalized to a 4-week rate) observed during the Maintenance Phase in participants treated with UX007 versus placebo, as recorded by the subject/caregiver in an event-based daily Glut1 DS symptom diary.
    End point type
    Primary
    End point timeframe
    Maintenance Phase (up to Week 22)
    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: Statistical analyses are attached as a pdf.
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    43
    42
    Units: movement disorder events per 4 weeks
        median (full range (min-max))
    14.26 (0.0 to 112.0)
    11.81 (0.5 to 112.0)
    Attachments
    Untitled (Filename: Statistical Analysis for Maintenance Phase Movement Disorder Frequency.docx)
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

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    End point title
    Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs [2]
    End point description
    An Adverse Event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. Serious adverse events (SAE) was defined as an AE that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); a congenital anomaly/birth defect; other important medical event. All reported AEs with with a start date that occurred or worsened in severity on or after the first dose of study drug in the corresponding treatment period and before the first dose of study drug in the next treatment period were defined as TEAEs. AEs were graded as 1=mild, 2=moderate, 3=severe, 4=life=threatening, 5=death.
    End point type
    Primary
    End point timeframe
    From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, and 305.0 (122.71) days for open-label UX007.
    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 are presented per protocol.
    End point values
    Safety Analysis Set: Double-Blind UX007 Safety Analysis Set: Double-Blind Placebo Safety Analysis Set: Open-Label UX007
    Number of subjects analysed
    43
    42
    33
    Units: subjects
        TEAEs
    40
    34
    28
        Serious TEAEs
    2
    1
    2
        Treatment-Related TEAEs
    33
    19
    17
        Treatment-Related Serious TEAEs
    1
    0
    0
        Grade 3 or 4 TEAEs
    4
    3
    3
        Grade 4 TEAEs
    0
    0
    0
        Gastrointestinal TEAEs
    32
    17
    18
        TEAEs Leading to Treatment Discontinuation
    2
    1
    0
        TEAEs Leading to Study Discontinuation
    2
    1
    0
        TEAEs Leading to Death
    0
    0
    0
    No statistical analyses for this end point

    Primary: Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period

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    End point title
    Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period [3]
    End point description
    The C-SSRS is a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, and self-injurious behavior with no suicidal intent (yes or no responses). Positive responses (i.e., 'Yes') to C-SSRS questions correspond to events in these categories with the exception of the category 'No events'. Suicidal ideation includes the following subcategories: passive; active-nonspecific; active-method/no intent/no plan; active-intent/with or without method/no plan; active-method/intent/plan. Suicidal behavior includes the following subcategories: suicide attempt; interrupted attempt; aborted attempt; preparatory actions toward immanent suicidal behaviors; completed suicide. Suicidal ideation and/or suicidal behavior category includes participants with positive responses in the category suicidal ideation and/or suicidal behavior.
    End point type
    Primary
    End point timeframe
    Baseline, up to Week 22
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics are presented per protocol.
    End point values
    Safety Analysis Set: Double-Blind UX007 Safety Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    40 [4]
    40 [5]
    Units: participants
        BL: No Events
    38
    38
        PB: No Events
    40
    39
        BL: Suicidal Ideation
    1
    1
        PB: Suicidal Ideation
    0
    0
        BL: Suicidal Behavior
    1
    1
        PB: Suicidal Behavior
    0
    1
        BL: Suicidal Ideation and/or Behavior
    2
    2
        PB: Suicidal Ideation and/or Behavior
    0
    1
        BL: Self-Injurious Behavior, No Suicidal Intent
    1
    1
        PB: Self-Injurious Behavior, No Suicidal Intent
    0
    1
    Notes
    [4] - Subjects with a baseline (BL) and postbaseline (PB) assessment
    [5] - Subjects with a baseline (BL) and postbaseline (PB) assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

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    End point title
    Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10
    End point description
    Walking capacity and endurance, as determined by the distance in meters walked in 12 minutes during the 12MWT.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    36 [6]
    38 [7]
    Units: meters
        least squares mean (standard error)
    -15.9 ± 25.63
    -33.0 ± 24.91
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in 12MWT Distance.docx)
    Notes
    [6] - subjects with an assessment
    [7] - subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10

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    End point title
    Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Physical Function Mobility Domain, increases in score indicate greater mobility.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [8]
    25 [9]
    Units: T-score
        least squares mean (standard error)
    -0.9 ± 0.67
    -0.9 ± 0.65
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Physical Function Score.docx)
    Notes
    [8] - adult subjects with an assessment
    [9] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [10]
    25 [11]
    Units: T-score
        least squares mean (standard error)
    2.9 ± 1.40
    0.9 ± 1.36
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score.docx)
    Notes
    [10] - adult subjects with an assessment
    [11] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Sleep Disturbance Domain, decreases in score indicate less sleep disturbance.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [12]
    25 [13]
    Units: T-score
        least squares mean (standard error)
    0.4 ± 1.24
    0.7 ± 1.20
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance.docx)
    Notes
    [12] - adult subjects with an assessment
    [13] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in scores indicate less pain interference.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [14]
    25 [15]
    Units: T-score
        least squares mean (standard error)
    4.5 ± 1.64
    3.7 ± 1.58
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference.docx)
    Notes
    [14] - adult subjects with an assessment
    [15] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. The Cognitive Function Domain measures cognitive function impairment. Decreases in score indicate less cognitive function impairment.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [16]
    25 [17]
    Units: T-score
        least squares mean (standard error)
    2.0 ± 1.29
    1.2 ± 1.25
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function.docx)
    Notes
    [16] - adult subjects with an assessment
    [17] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Social Roles and Activities Domain, decreases in score indicate worse /less or decrease of performance in social roles and activities.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [18]
    25 [19]
    Units: T-score
        least squares mean (standard error)
    -4.1 ± 1.35
    -2.3 ± 1.32
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities.docx)
    Notes
    [18] - adult subjects with an assessment
    [19] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Anxiety Domain, decreases in scores indicate less anxiety.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    23 [20]
    25 [21]
    Units: T-score
        least squares mean (standard error)
    3.1 ± 1.49
    0.5 ± 1.45
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score.docx)
    Notes
    [20] - adult subjects with an assessment
    [21] - adult subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Mobility Domain, decreases in score indicate less mobility.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    16 [22]
    13 [23]
    Units: T-score
        least squares mean (standard error)
    -1.0 ± 1.62
    0.0 ± 1.73
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Mobility Score.docx)
    Notes
    [22] - pediatric subjects with an assessment
    [23] - pediatric subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Upper Extremity Domain, decreases in score indicate less upper extremity movement.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    16 [24]
    13 [25]
    Units: T-score
        least squares mean (standard deviation)
    -0.4 ± 1.91
    1.3 ± 2.11
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Upper Extremity.docx)
    Notes
    [24] - pediatric subjects with an assessment
    [25] - pediatric subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    16 [26]
    13 [27]
    Units: T-score
        least squares mean (standard error)
    -1.8 ± 2.40
    -0.6 ± 2.64
    Attachments
    Untitled (Filename: Statistical Analysis 2 for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Fatigue.docx)
    Notes
    [26] - pediatric subjects with an assessment
    [27] - pediatric subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in score indicate less pain interference.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    16 [28]
    13 [29]
    Units: T-score
        least squares mean (standard error)
    3.2 ± 1.84
    1.6 ± 1.96
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Pain Interference.docx)
    Notes
    [28] - pediatric subjects with an assessment
    [29] - pediatric subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10

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    End point title
    Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10
    End point description
    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Peer Relationships Domain, decreases in score indicate worse functioning in peer relationships.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    16 [30]
    13 [31]
    Units: T-score
        least squares mean (standard error)
    2.0 ± 1.57
    -0.0 ± 1.64
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Peer Relationships.docx)
    Notes
    [30] - pediatric subjects with an assessment
    [31] - pediatric subjects with an assessment
    No statistical analyses for this end point

    Secondary: Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10

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    End point title
    Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10
    End point description
    Participant/caregiver global impression of change in clinical status using the CGI-I. The CGI-I is a 7-point scale that assesses how much the participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much better; 2=much better; 3=a little better; 4=no change; 5=a little worse; 6=much worse; 7=very much worse.
    End point type
    Secondary
    End point timeframe
    Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    38
    40
    Units: score on a scale
        least squares mean (standard error)
    3.5 ± 0.20
    3.6 ± 0.20
    Attachments
    Untitled (Filename: Statistical Analysis for Clinical Global Impression - Improvement (CGI-I).docx)
    No statistical analyses for this end point

    Secondary: Duration of Movement Disorder Events During Maintenance Phase

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    End point title
    Duration of Movement Disorder Events During Maintenance Phase
    End point description
    Duration of disabling paroxysmal movement disorder events observed during the Maintenance Period of treatment, as recorded by the subject/caregiver in an event-based daily electronic Glut1 DS symptom diary.
    End point type
    Secondary
    End point timeframe
    Maintenance Phase (up to 22 weeks)
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    43
    42
    Units: hours
        arithmetic mean (standard deviation)
    0.9 ± 1.98
    0.7 ± 1.53
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10

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    End point title
    Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10
    End point description
    Cognitive function as measured by the CANTAB. CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SSP Span Length assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    13
    14
    Units: units on a scale
        least squares mean (standard error)
    0.1 ± 0.31
    0.6 ± 0.29
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP).docx)
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10

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    End point title
    Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10
    End point description
    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMBE assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    13
    14
    Units: units on a scale
        least squares mean (standard error)
    -0.2 ± 2.94
    0.2 ± 2.83
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE).docx)
    No statistical analyses for this end point

    Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10

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    End point title
    Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10
    End point description
    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMS assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    13 [32]
    14 [33]
    Units: units on a scale
        least squares mean (standard error)
    0.6 ± 0.77
    -0.4 ± 0.74
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS).docx)
    Notes
    [32] - subjects with an assessment
    [33] - subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10

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    End point title
    Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10
    End point description
    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PALTEA assesses the cognitive domain of episodic memory/new learning, with scores on a discrete, ordinal scale from 0 to 137; lower scores indicate better function.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    13 [34]
    15 [35]
    Units: units on a scale
        least squares mean (standard error)
    -2.0 ± 4.74
    -8.5 ± 4.41
    Attachments
    Untitled (Filename: Statistical Analysis 2 for Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA).docx)
    Notes
    [34] - subjects with an assessment
    [35] - subjects with an assessment
    No statistical analyses for this end point

    Secondary: Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10

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    End point title
    Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10
    End point description
    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PALFTMS assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function.
    End point type
    Secondary
    End point timeframe
    Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10
    End point values
    Full Analysis Set: Double-Blind UX007 Full Analysis Set: Double-Blind Placebo
    Number of subjects analysed
    13 [36]
    15 [37]
    Units: units on a scale
        least squares mean (standard error)
    -0.1 ± 1.12
    0.9 ± 1.04
    Attachments
    Untitled (Filename: Statistical Analysis for Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS).docx)
    Notes
    [36] - subjects with an assessment
    [37] - subjects with an assessment
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, respectively, and 305.0 (122.71) days for open-label UX007.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    DB UX007
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.

    Reporting group title
    OL UX007
    Reporting group description
    Open-Label Extension Phase: Subjects continued UX007 treatment for up to 3 years.

    Reporting group title
    DB Placebo
    Reporting group description
    Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks.

    Serious adverse events
    DB UX007 OL UX007 DB Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 33 (6.06%)
    1 / 42 (2.38%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Head Injury
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 33 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Movement Disorder
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 33 (3.03%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychomotor Hyperactivity
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 33 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Limb Asymmetry
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 33 (3.03%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    DB UX007 OL UX007 DB Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    36 / 43 (83.72%)
    22 / 33 (66.67%)
    26 / 42 (61.90%)
    Investigations
    Blood Ketone Body Increased
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 33 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    3
    0
    2
    Weight Increased
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 33 (6.06%)
    1 / 42 (2.38%)
         occurrences all number
    3
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 33 (9.09%)
    0 / 42 (0.00%)
         occurrences all number
    2
    4
    0
    Oropharyngeal Pain
         subjects affected / exposed
    4 / 43 (9.30%)
    1 / 33 (3.03%)
    3 / 42 (7.14%)
         occurrences all number
    4
    1
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 33 (6.06%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    2
    Dyskinesia
         subjects affected / exposed
    3 / 43 (6.98%)
    3 / 33 (9.09%)
    2 / 42 (4.76%)
         occurrences all number
    3
    4
    2
    Headache
         subjects affected / exposed
    7 / 43 (16.28%)
    6 / 33 (18.18%)
    6 / 42 (14.29%)
         occurrences all number
    15
    17
    12
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 43 (6.98%)
    3 / 33 (9.09%)
    5 / 42 (11.90%)
         occurrences all number
    3
    5
    5
    Gait Disturbance
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 33 (6.06%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    1
    Pyrexia
         subjects affected / exposed
    4 / 43 (9.30%)
    2 / 33 (6.06%)
    1 / 42 (2.38%)
         occurrences all number
    5
    2
    1
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 33 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    4
    0
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 33 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    10
    0
    0
    Abdominal Pain
         subjects affected / exposed
    6 / 43 (13.95%)
    5 / 33 (15.15%)
    1 / 42 (2.38%)
         occurrences all number
    9
    6
    1
    Abdominal Pain Upper
         subjects affected / exposed
    14 / 43 (32.56%)
    7 / 33 (21.21%)
    6 / 42 (14.29%)
         occurrences all number
    35
    22
    11
    Anal Incontinence
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 33 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    4
    0
    0
    Constipation
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 33 (9.09%)
    1 / 42 (2.38%)
         occurrences all number
    1
    5
    1
    Diarrhoea
         subjects affected / exposed
    22 / 43 (51.16%)
    9 / 33 (27.27%)
    5 / 42 (11.90%)
         occurrences all number
    50
    46
    12
    Nausea
         subjects affected / exposed
    7 / 43 (16.28%)
    4 / 33 (12.12%)
    5 / 42 (11.90%)
         occurrences all number
    10
    6
    7
    Vomiting
         subjects affected / exposed
    13 / 43 (30.23%)
    8 / 33 (24.24%)
    8 / 42 (19.05%)
         occurrences all number
    23
    14
    11
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    5 / 43 (11.63%)
    1 / 33 (3.03%)
    1 / 42 (2.38%)
         occurrences all number
    5
    1
    1
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 33 (3.03%)
    0 / 42 (0.00%)
         occurrences all number
    3
    1
    0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 33 (6.06%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    1
    Influenza
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 33 (6.06%)
    0 / 42 (0.00%)
         occurrences all number
    3
    3
    0
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    5 / 43 (11.63%)
    2 / 33 (6.06%)
    2 / 42 (4.76%)
         occurrences all number
    7
    4
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Sep 2018
    • Section 4.6 was included to define subgroups for analysis. Section 8.8.1 and Appendix A were updated with the statistical methods for analyses of the subgroups defined in Section 4.6. • Revised Section 5.8 to define PROMIS final T scores from the PROMIS online scoring system. • Revised SAP to align with changes to the Protocol made in Amendment 3.

    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
    The status of studies in GB is no longer updated from 1.1.2021
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