Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02960217
Recruitment Status : Terminated (Study was halted prematurely due to lack of efficacy.)
First Posted : November 9, 2016
Results First Posted : April 24, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Interventions Drug: UX007
Drug: Placebo
Enrollment 44
Recruitment Details  
Pre-assignment Details

During a 6-week Run-in Period, participants recorded disabling paroxysmal movement disorder events in a daily electronic Glut1 DS movement disorder diary.

One participant was randomized but did not receive any treatment due to a protocol violation; this participant was not included in any analysis population.

Arm/Group Title Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007
Hide Arm/Group Description

Double-Blind Maintenance Phase: Participants 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.

Participants had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.

Double-Blind Maintenance Phase: Participants 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.

Participants had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.

Period Title: Maintenance Phase: Treatment Period 1
Started [1] 22 21
Completed 21 21
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
[1]
Randomized and treated
Period Title: Maintenance Phase: Crossover Washout
Started 21 21
Completed 21 21
Not Completed 0 0
Period Title: Maintenance Phase: Treatment Period 2
Started 21 21
Completed 20 18
Not Completed 1 3
Reason Not Completed
Adverse Event             0             1
Withdrawal by Subject             0             1
Lack of Efficacy             1             0
Other, Not Specified             0             1
Period Title: Open-Label Extension Phase
Started 20 13 [1]
Completed 0 0
Not Completed 20 13
Reason Not Completed
Adverse Event             1             0
Sponsor Decision             18             11
Lack of Efficacy             1             1
Other, Not Specified             0             1
[1]
5 participants completed the double blind period but did not continue in the open label period.
Arm/Group Title Double-Blind UX007 Followed by Placebo Double-Blind Placebo Followed by UX007 Total
Hide Arm/Group Description

Double-Blind Maintenance Period: Participants 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.

Participants had the option of rolling into the Open-Label Extension Period, to continue UX007 treatment for up to 3 years.

Double-Blind Maintenance Period: Participants 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.

Participants had the option of rolling into the Open-Label Extension Period, to continue UX007 treatment for up to 3 years.

Total of all reporting groups
Overall Number of Baseline Participants 22 21 43
Hide Baseline Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 21 participants 43 participants
23.41  (13.156) 18.37  (5.730) 20.95  (10.425)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
< 18 years old
7
  31.8%
9
  42.9%
16
  37.2%
>/= 18 years old
15
  68.2%
12
  57.1%
27
  62.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
Female
12
  54.5%
12
  57.1%
24
  55.8%
Male
10
  45.5%
9
  42.9%
19
  44.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
Hispanic or Latino
1
   4.5%
0
   0.0%
1
   2.3%
Not Hispanic or Latino
17
  77.3%
17
  81.0%
34
  79.1%
Unknown or Not Reported
4
  18.2%
4
  19.0%
8
  18.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
Black or African American
0
   0.0%
1
   4.8%
1
   2.3%
White
18
  81.8%
16
  76.2%
34
  79.1%
Missing
4
  18.2%
4
  19.0%
8
  18.6%
1.Primary Outcome
Title Maintenance Phase Movement Disorder Frequency
Hide 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.
Time Frame Maintenance Phase (up to Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 43 42
Median (Full Range)
Unit of Measure: movement disorder events per 4 weeks
14.26
(0.0 to 112.0)
11.81
(0.5 to 112.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Participants completing both UX007 treatment period and placebo period (n=42). Per protocol, when the normality assumption is not met (p value for Wilk-Shapiro test < 0.05), Wilcoxon rank-sum test will be considered as the primary analysis to assess treatment difference in movement disorder event frequency.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2684
Comments Hodges-Lehmann estimate of the location shift with 95% confidence interval (CI) and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
-1.12 to 4.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilk-Shapiro test for normality
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
Hide 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo Open-Label UX007
Hide Arm/Group Description:
Double-Blind Maintenance Phase: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Double-Blind Maintenance Phase: Participants received placebo for 10 weeks.
Open-Label Extension Phase: Participants continued UX007 treatment for up to 3 years.
Overall Number of Participants Analyzed 43 42 33
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
40
  93.0%
34
  81.0%
28
  84.8%
Serious TEAEs
2
   4.7%
1
   2.4%
2
   6.1%
Treatment-Related TEAEs
33
  76.7%
19
  45.2%
17
  51.5%
Treatment-Related Serious TEAEs
1
   2.3%
0
   0.0%
0
   0.0%
Grade 3 or 4 TEAEs
4
   9.3%
3
   7.1%
3
   9.1%
Grade 4 TEAEs
0
   0.0%
0
   0.0%
0
   0.0%
Gastrointestinal TEAEs
32
  74.4%
17
  40.5%
18
  54.5%
TEAEs Leading to Treatment Discontinuation
2
   4.7%
1
   2.4%
0
   0.0%
TEAEs Leading to Study Discontinuation
2
   4.7%
1
   2.4%
0
   0.0%
TEAEs Leading to Death
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period
Hide 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.
Time Frame Baseline, up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with a baseline (BL) and postbaseline (PB) assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 40 40
Measure Type: Count of Participants
Unit of Measure: Participants
BL: No Events
38
  95.0%
38
  95.0%
PB: No Events
40
 100.0%
39
  97.5%
BL: Suicidal Ideation
1
   2.5%
1
   2.5%
PB: Suicidal Ideation
0
   0.0%
0
   0.0%
BL: Suicidal Behavior
1
   2.5%
1
   2.5%
PB: Suicidal Behavior
0
   0.0%
1
   2.5%
BL: Suicidal Ideation and/or Behavior
2
   5.0%
2
   5.0%
PB: Suicidal Ideation and/or Behavior
0
   0.0%
1
   2.5%
BL: Self-Injurious Behavior, No Suicidal Intent
1
   2.5%
1
   2.5%
PB: Self-Injurious Behavior, No Suicidal Intent
0
   0.0%
1
   2.5%
4.Secondary Outcome
Title Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10
Hide Description Walking capacity and endurance, as determined by the distance in meters walked in 12 minutes during the 12MWT.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 36 38
Least Squares Mean (Standard Error)
Unit of Measure: meters
-15.9  (25.63) -33.0  (24.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=34).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6419
Comments Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value 25.00
Confidence Interval (2-Sided) 95%
-62.5 to 91.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
5.Secondary Outcome
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
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-0.9  (0.67) -0.9  (0.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9513
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.0 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8214
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
6.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
2.9  (1.40) 0.9  (1.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1572
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-0.8 to 4.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8451
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
7.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
0.4  (1.24) 0.7  (1.20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8345
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-3.8 to 3.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2894
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
8.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
4.5  (1.64) 3.7  (1.58)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=21).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4898
Comments Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-5.4 to 5.8
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
2.0  (1.29) 1.2  (1.25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5853
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-2.2 to 3.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1066
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
10.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-4.1  (1.35) -2.3  (1.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1875
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-4.6 to 1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2034
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
11.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 23 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
3.1  (1.49) 0.5  (1.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1138
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-0.7 to 5.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1478
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
12.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 16 13
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-1.0  (1.62) 0.0  (1.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5505
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-4.6 to 2.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4459
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
13.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 16 13
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-0.4  (1.91) 1.3  (2.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5544
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-8.1 to 4.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1104
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
14.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 16 13
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-1.8  (2.40) -0.6  (2.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7145
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-8.5 to 6.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8255
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
15.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 16 13
Least Squares Mean (Standard Error)
Unit of Measure: T-score
3.2  (1.84) 1.6  (1.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4176
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-2.5 to 5.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6557
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
16.Secondary Outcome
Title Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 16 13
Least Squares Mean (Standard Error)
Unit of Measure: T-score
2.0  (1.57) -0.0  (1.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0935
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-0.4 to 4.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7267
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
17.Secondary Outcome
Title Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10
Hide 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.
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 38 40
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
3.5  (0.20) 3.6  (0.20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8329
Comments Based on an ANCOVA model including covariate for study baseline CGI-S score, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2348
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
18.Secondary Outcome
Title Duration of Movement Disorder Events During Maintenance Phase
Hide 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.
Time Frame Maintenance Phase (up to 22 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 43 42
Mean (Standard Deviation)
Unit of Measure: hours
0.9  (1.98) 0.7  (1.53)
19.Secondary Outcome
Title Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 13 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.1  (0.31) 0.6  (0.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0315
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=13).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2425
Comments Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.5 to 0.5
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 13 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.2  (2.94) 0.2  (2.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0072
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=12).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-14.5 to 13.5
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 13 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.6  (0.77) -0.4  (0.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1076
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.3 to 2.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7698
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 13 15
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (4.74) -8.5  (4.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0138
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=13).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3907
Comments Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
Method Wilcoxon Rank Sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate (Median Diff.)
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-3.5 to 20.5
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug. Participants who had an assessment.
Arm/Group Title Double-Blind UX007 Double-Blind Placebo
Hide Arm/Group Description:
UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.
Placebo for 10 weeks.
Overall Number of Participants Analyzed 13 15
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.1  (1.12) 0.9  (1.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5233
Comments Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-4.4 to 2.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind UX007, Double-Blind Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6918
Comments [Not Specified]
Method Wilk-Shapiro Test for Normality
Comments [Not Specified]
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DB UX007 DB Placebo OL UX007
Hide Arm/Group Description Double-Blind Maintenance Phase: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Double-Blind Maintenance Phase: Participants received placebo for 10 weeks. Open-Label Extension Phase: Participants continued UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.
All-Cause Mortality
DB UX007 DB Placebo OL UX007
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)   0/42 (0.00%)   0/33 (0.00%) 
Hide Serious Adverse Events
DB UX007 DB Placebo OL UX007
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/43 (4.65%)   1/42 (2.38%)   2/33 (6.06%) 
Injury, poisoning and procedural complications       
Head Injury  1  1/43 (2.33%)  0/42 (0.00%)  0/33 (0.00%) 
Musculoskeletal and connective tissue disorders       
Limb Asymmetry  1  0/43 (0.00%)  0/42 (0.00%)  1/33 (3.03%) 
Nervous system disorders       
Movement Disorder  1  1/43 (2.33%)  0/42 (0.00%)  1/33 (3.03%) 
Psychomotor Hyperactivity  1  0/43 (0.00%)  1/42 (2.38%)  0/33 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DB UX007 DB Placebo OL UX007
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/43 (83.72%)   26/42 (61.90%)   22/33 (66.67%) 
Gastrointestinal disorders       
Abdominal Discomfort  1  4/43 (9.30%)  0/42 (0.00%)  0/33 (0.00%) 
Abdominal Pain  1  6/43 (13.95%)  1/42 (2.38%)  5/33 (15.15%) 
Abdominal Pain Upper  1  14/43 (32.56%)  6/42 (14.29%)  7/33 (21.21%) 
Anal Incontinence  1  3/43 (6.98%)  0/42 (0.00%)  0/33 (0.00%) 
Constipation  1  1/43 (2.33%)  1/42 (2.38%)  3/33 (9.09%) 
Diarrhoea  1  22/43 (51.16%)  5/42 (11.90%)  9/33 (27.27%) 
Nausea  1  7/43 (16.28%)  5/42 (11.90%)  4/33 (12.12%) 
Vomiting  1  13/43 (30.23%)  8/42 (19.05%)  8/33 (24.24%) 
General disorders       
Fatigue  1  3/43 (6.98%)  5/42 (11.90%)  3/33 (9.09%) 
Gait Disturbance  1  0/43 (0.00%)  1/42 (2.38%)  2/33 (6.06%) 
Pyrexia  1  4/43 (9.30%)  1/42 (2.38%)  2/33 (6.06%) 
Infections and infestations       
Gastroenteritis  1  3/43 (6.98%)  0/42 (0.00%)  1/33 (3.03%) 
Gastroenteritis Viral  1  0/43 (0.00%)  1/42 (2.38%)  2/33 (6.06%) 
Influenza  1  3/43 (6.98%)  0/42 (0.00%)  2/33 (6.06%) 
Viral Upper Respiratory Tract Infection  1  5/43 (11.63%)  2/42 (4.76%)  2/33 (6.06%) 
Investigations       
Blood Ketone Body Increased  1  3/43 (6.98%)  2/42 (4.76%)  0/33 (0.00%) 
Weight Increased  1  3/43 (6.98%)  1/42 (2.38%)  2/33 (6.06%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  5/43 (11.63%)  1/42 (2.38%)  1/33 (3.03%) 
Nervous system disorders       
Dizziness  1  1/43 (2.33%)  2/42 (4.76%)  2/33 (6.06%) 
Dyskinesia  1  3/43 (6.98%)  2/42 (4.76%)  3/33 (9.09%) 
Headache  1  7/43 (16.28%)  6/42 (14.29%)  6/33 (18.18%) 
Psychiatric disorders       
Aggression  1  4/43 (9.30%)  0/42 (0.00%)  0/33 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/43 (4.65%)  0/42 (0.00%)  3/33 (9.09%) 
Oropharyngeal Pain  1  4/43 (9.30%)  3/42 (7.14%)  1/33 (3.03%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8567
EMail: medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02960217    
Other Study ID Numbers: UX007G-CL301
First Submitted: November 7, 2016
First Posted: November 9, 2016
Results First Submitted: April 8, 2020
Results First Posted: April 24, 2020
Last Update Posted: June 16, 2020