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Trial record 1 of 1 for:    NCT02731690
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A Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER; UX001) Tablets in Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy [HIBM]) Patients With Severe Ambulatory Impairment

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ClinicalTrials.gov Identifier: NCT02731690
Recruitment Status : Terminated
First Posted : April 7, 2016
Results First Posted : February 19, 2019
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hereditary Inclusion Body Myopathy
Distal Myopathy With Rimmed Vacuoles
Distal Myopathy, Nonaka Type
GNE Myopathy
Quadriceps Sparing Myopathy
Inclusion Body Myopathy 2
Intervention Drug: Aceneuramic Acid Extended-Release
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Period Title: Overall Study
Started 42
Completed 12
Not Completed 30
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             3
Discontinuation of Study by Sponsor             26
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Baseline Participants 42
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants
46.0  (13.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants
Female
25
  59.5%
Male
17
  40.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
42
 100.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 42 participants
31
  73.8%
Asian Number Analyzed 42 participants
2
   4.8%
Other (Not Specified) Number Analyzed 42 participants
9
  21.4%
Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 41 participants
10.63  (7.816)
[1]
Measure Description: GNEM-FAS Expanded Version Mobility subscale scores have 13 items and range from 0 to 52 with higher scores representing greater mobility.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Upper Extremity Domain Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 41 participants
15.20  (8.897)
[1]
Measure Description: GNEM-FAS Expanded Version Upper Extremity subscale scores have 9 items and range from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Self-Care Domain Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 41 participants
13.00  (7.413)
[1]
Measure Description: GNEM-FAS Expanded Version Self-Care subscale scores have 8 items range from 0 to 32 with higher scores representing greater independence with functional care activities.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Total Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 41 participants
38.83  (23.116)
[1]
Measure Description: GNEM-FAS Expanded Version Total Score were calculated as the sum of the subscale Scores range from 0 to 120 with higher scores representing greater independence with functional activities.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Hand-Held Dynamometry (HHD) Raw Strength: Average Grip   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 41 participants
5.535  (7.6778)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kilogram-force [kgf]) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Average Shoulder Abduction   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 41 participants
3.880  (4.4583)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Average Wrist Extension   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 41 participants
3.532  (3.5177)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Lower Extremity Muscle Strength: Average Knee Extension   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 41 participants
10.50  (8.001)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Key Pinch   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 41 participants
1.790  (2.1614)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Hide Description An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction 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); congenital anomaly/birth defect. TEAEs were defined as any AE that occurred after the first dose of study drug.
Time Frame 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
30
  71.4%
Serious TEAEs
1
   2.4%
TEAEs Causing Study Drug Discontinuation
1
   2.4%
TEAEs Causing Study Discontinuation
1
   2.4%
2.Secondary Outcome
Title Number of Participants Taking Prior and Concomitant Medications
Hide Description Prior medications are any medications which started before the date of the first dose of investigational product. Concomitant medications are any medications that are taken on or after the date of the first dose of investigational product excluding concomitant medications started after the date of the last dose of investigational product.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Count of Participants
Unit of Measure: Participants
Prior Medications 31
Concomitant Medications 33
3.Secondary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations
Hide Description Complete physical examinations included assessments of general appearance; head, eyes, ears, nose, and throat; the cardiovascular, dermatologic, lymphatic, respiratory, GI, musculoskeletal, and neurologic systems. The neurologic system examination included assessments of cognition, cranial nerves, motor function, coordination and gait, reflexes, and sensory function. Brief physical examinations included assessments of general appearance, cardiovascular and respiratory systems, and a focus on any presenting complaints.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: participants
0
4.Secondary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline In Vital Signs
Hide Description Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: participants
0
5.Secondary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results
Hide Description The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: participants
Hematology 0
Clinical Chemistry 2
Urinalysis 0
6.Secondary Outcome
Title Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline
Hide Description As evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS), a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses).
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 42
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Suicidal Behaviors: Baseline 1
Overall Suicidal Behaviors: Post-Baseline 0
Non-Suicide Self-Injurious Behavior: Baseline 0
Non-Suicide Self-Injurious Behavior: Post-Baseline 0
Completed Suicide: Post-Baseline 0
Overall Suicidal Ideation: Baseline 7
Overall Suicidal Ideation: Post-Baseline 1
7.Secondary Outcome
Title Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time
Hide Description GNEM-FAS Expanded Version Mobility subscale scores have 13 items and range from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 12
0.16
(-0.33 to 0.64)
Week 24
-0.65
(-1.56 to 0.27)
Week 36
-0.69
(-1.57 to 0.18)
Week 48
-1.03
(-2.15 to 0.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5303
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1646
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1189
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0706
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time
Hide Description GNEM-FAS Expanded Version Upper Extremity subscale scores have 9 items and range from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 12
0.57
(-0.05 to 1.19)
Week 24
-0.62
(-1.50 to 0.26)
Week 36
-0.51
(-1.58 to 0.55)
Week 48
-1.91
(-3.93 to 0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0715
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1697
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3428
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0642
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time
Hide Description GNEM-FAS Expanded Version Self-Care subscale scores have 8 items range from 0 to 32 with higher scores representing greater independence with functional care activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 12
-0.39
(-0.79 to 0.01)
Week 24
-0.71
(-1.43 to 0.01)
Week 36
-0.83
(-1.64 to -0.02)
Week 48
-0.40
(-1.78 to 0.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0568
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0533
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0459
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5678
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time
Hide Description GNEM-FAS Expanded Version Total Score were calculated as the sum of the subscale Scores range from 0 to 120 with higher scores representing greater independence with functional activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 12
0.35
(-0.89 to 1.58)
Week 24
-1.95
(-3.87 to -0.03)
Week 36
-2.02
(-4.46 to 0.42)
Week 48
-3.34
(-6.90 to 0.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5810
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0465
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1047
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0661
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in HHD Raw Strength (Grip) Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 12
0.258
(-0.103 to 0.620)
Week 24
0.128
(-0.377 to 0.632)
Week 36
0.038
(-0.724 to 0.799)
Week 48
-0.261
(-1.325 to 0.803)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1615
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6201
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9229
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6307
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 12
0.339
(0.085 to 0.592)
Week 24
0.379
(-0.228 to 0.987)
Week 36
0.437
(0.075 to 0.800)
Week 48
-0.277
(-0.698 to 0.144)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2213
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0180
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1970
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 12
0.235
(-0.024 to 0.495)
Week 24
0.152
(-0.486 to 0.791)
Week 36
0.358
(-0.228 to 0.943)
Week 48
-0.123
(-0.924 to 0.678)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0752
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Statistical Test of Hypothesis P-Value 0.6403
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Statistical Test of Hypothesis P-Value 0.2316
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7635
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 12
0.80
(-0.12 to 1.73)
Week 24
1.35
(0.36 to 2.33)
Week 36
2.05
(0.52 to 3.58)
Week 48
2.45
(0.01 to 4.88)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0872
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0086
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX001 6g/Day
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0489
Comments Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Method GEE model
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in HHD Raw Strength (Key Pinch) Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
Time Frame Baseline, Weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement at given time point.
Arm/Group Title UX001 6g/Day
Hide Arm/Group Description:
Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Number of Participants Analyzed 41
Mean (Standard Deviation)
Unit of Measure: kgf
Week 12 Number Analyzed 41 participants
0.110  (0.7083)
Week 24 Number Analyzed 30 participants
0.112  (0.6534)
Week 36 Number Analyzed 23 participants
0.049  (0.8090)
Week 48 Number Analyzed 11 participants
0.318  (0.9509)
Time Frame 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ace-ER 6 g/Day
Hide Arm/Group Description Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
All-Cause Mortality
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   0/42 (0.00%) 
Hide Serious Adverse Events
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   1/42 (2.38%) 
Infections and infestations   
Pyelonephritis  1  1/42 (2.38%) 
Sepsis  1  1/42 (2.38%) 
Renal and urinary disorders   
Nephrolithiasis  1  1/42 (2.38%) 
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   26/42 (61.90%) 
Gastrointestinal disorders   
Abdominal distension  1  7/42 (16.67%) 
Abdominal pain upper  1  6/42 (14.29%) 
Dyspepsia  1  3/42 (7.14%) 
Dysphagia  1  3/42 (7.14%) 
Flatulence  1  7/42 (16.67%) 
Nausea  1  3/42 (7.14%) 
General disorders   
Fatigue  1  3/42 (7.14%) 
Oedema peripheral  1  3/42 (7.14%) 
Infections and infestations   
Upper respiratory tract infection  1  7/42 (16.67%) 
Urinary tract infection  1  3/42 (7.14%) 
Injury, poisoning and procedural complications   
Fall  1  4/42 (9.52%) 
Metabolism and nutrition disorders   
Diabetes mellitus  1  3/42 (7.14%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/42 (7.14%) 
Back pain  1  3/42 (7.14%) 
Muscular weakness  1  4/42 (9.52%) 
Pain in extremity  1  4/42 (9.52%) 
Nervous system disorders   
Headache  1  3/42 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  3/42 (7.14%) 
1
Term from vocabulary, MedDRA 17.1
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: 1-888-756-8657
EMail: medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02731690    
Other Study ID Numbers: UX001-CL203
First Submitted: March 24, 2016
First Posted: April 7, 2016
Results First Submitted: January 7, 2019
Results First Posted: February 19, 2019
Last Update Posted: February 19, 2019