Trial Outcomes & Findings for 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 (NCT NCT02731690)

NCT ID: NCT02731690

Last Updated: 2019-02-19

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
• Results posted on: 2019-02-19

Participant Flow

Participant milestones

Measure	UX001 6g/Day Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Study STARTED	42
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	30

Reasons for withdrawal

Measure	UX001 6g/Day Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	3
Overall Study Discontinuation of Study by Sponsor	26

Baseline Characteristics

Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

Baseline characteristics by cohort

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Age, Continuous	46.0 years STANDARD_DEVIATION 13.97 • n=42 Participants
Sex: Female, Male Female	25 Participants n=42 Participants
Sex: Female, Male Male	17 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=42 Participants
Race/Ethnicity, Customized White	31 Participants n=42 Participants
Race/Ethnicity, Customized Asian	2 Participants n=42 Participants
Race/Ethnicity, Customized Other (Not Specified)	9 Participants n=42 Participants
Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score	10.63 units on a scale STANDARD_DEVIATION 7.816 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Upper Extremity Domain Score	15.20 units on a scale STANDARD_DEVIATION 8.897 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Self-Care Domain Score	13.00 units on a scale STANDARD_DEVIATION 7.413 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
GNEM-FAS Total Score	38.83 units on a scale STANDARD_DEVIATION 23.116 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
Hand-Held Dynamometry (HHD) Raw Strength: Average Grip	5.535 kgf STANDARD_DEVIATION 7.6778 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Average Shoulder Abduction	3.880 kgf STANDARD_DEVIATION 4.4583 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Average Wrist Extension	3.532 kgf STANDARD_DEVIATION 3.5177 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Lower Extremity Muscle Strength: Average Knee Extension	10.50 kgf STANDARD_DEVIATION 8.001 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
HHD Raw Strength: Key Pinch	1.790 kgf STANDARD_DEVIATION 2.1614 • n=41 Participants • Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

PRIMARY outcome

Timeframe: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAEs	30 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Serious TEAEs	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAEs Causing Study Discontinuation	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAEs Causing Study Drug Discontinuation	1 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants Taking Prior and Concomitant Medications Prior Medications	31 Participants
Number of Participants Taking Prior and Concomitant Medications Concomitant Medications	33 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations	0 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature.

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants With Clinically Significant Changes From Baseline In Vital Signs	0 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis.

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results Hematology	0 participants
Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results Clinical Chemistry	2 participants
Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results Urinalysis	0 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.

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).

Outcome measures

Measure	UX001 6g/Day n=42 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Overall Suicidal Ideation: Baseline	7 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Overall Suicidal Behaviors: Baseline	1 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Overall Suicidal Behaviors: Post-Baseline	0 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Non-Suicide Self-Injurious Behavior: Baseline	0 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Non-Suicide Self-Injurious Behavior: Post-Baseline	0 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Completed Suicide: Post-Baseline	0 Participants
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Overall Suicidal Ideation: Post-Baseline	1 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time Week 12	0.16 units on a scale Interval -0.33 to 0.64
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time Week 24	-0.65 units on a scale Interval -1.56 to 0.27
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time Week 36	-0.69 units on a scale Interval -1.57 to 0.18
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time Week 48	-1.03 units on a scale Interval -2.15 to 0.09

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time Week 12	0.57 units on a scale Interval -0.05 to 1.19
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time Week 24	-0.62 units on a scale Interval -1.5 to 0.26
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time Week 36	-0.51 units on a scale Interval -1.58 to 0.55
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time Week 48	-1.91 units on a scale Interval -3.93 to 0.11

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time Week 12	-0.39 units on a scale Interval -0.79 to 0.01
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time Week 24	-0.71 units on a scale Interval -1.43 to 0.01
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time Week 36	-0.83 units on a scale Interval -1.64 to -0.02
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time Week 48	-0.40 units on a scale Interval -1.78 to 0.98

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time Week 12	0.35 units on a scale Interval -0.89 to 1.58
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time Week 24	-1.95 units on a scale Interval -3.87 to -0.03
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time Week 36	-2.02 units on a scale Interval -4.46 to 0.42
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time Week 48	-3.34 units on a scale Interval -6.9 to 0.22

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in HHD Raw Strength (Grip) Over Time Week 12	0.258 kgf Interval -0.103 to 0.62
Change From Baseline in HHD Raw Strength (Grip) Over Time Week 24	0.128 kgf Interval -0.377 to 0.632
Change From Baseline in HHD Raw Strength (Grip) Over Time Week 36	0.038 kgf Interval -0.724 to 0.799
Change From Baseline in HHD Raw Strength (Grip) Over Time Week 48	-0.261 kgf Interval -1.325 to 0.803

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time Week 12	0.339 kgf Interval 0.085 to 0.592
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time Week 24	0.379 kgf Interval -0.228 to 0.987
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time Week 48	-0.277 kgf Interval -0.698 to 0.144
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time Week 36	0.437 kgf Interval 0.075 to 0.8

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time Week 12	0.235 kgf Interval -0.024 to 0.495
Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time Week 24	0.152 kgf Interval -0.486 to 0.791
Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time Week 48	-0.123 kgf Interval -0.924 to 0.678
Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time Week 36	0.358 kgf Interval -0.228 to 0.943

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time Week 36	2.05 kgf Interval 0.52 to 3.58
Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time Week 12	0.80 kgf Interval -0.12 to 1.73
Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time Week 24	1.35 kgf Interval 0.36 to 2.33
Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time Week 48	2.45 kgf Interval 0.01 to 4.88

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, and 48

Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement at given time point.

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.

Outcome measures

Measure	UX001 6g/Day n=41 Participants Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Change From Baseline in HHD Raw Strength (Key Pinch) Over Time Week 24	0.112 kgf Standard Deviation 0.6534
Change From Baseline in HHD Raw Strength (Key Pinch) Over Time Week 36	0.049 kgf Standard Deviation 0.8090
Change From Baseline in HHD Raw Strength (Key Pinch) Over Time Week 48	0.318 kgf Standard Deviation 0.9509
Change From Baseline in HHD Raw Strength (Key Pinch) Over Time Week 12	0.110 kgf Standard Deviation 0.7083

Adverse Events

Ace-ER 6 g/Day

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ace-ER 6 g/Day n=42 participants at risk Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Infections and infestations Pyelonephritis	2.4% 1/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Infections and infestations Sepsis	2.4% 1/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Renal and urinary disorders Nephrolithiasis	2.4% 1/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)

Other adverse events

Measure	Ace-ER 6 g/Day n=42 participants at risk Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen.
Gastrointestinal disorders Abdominal distension	16.7% 7/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Gastrointestinal disorders Abdominal pain upper	14.3% 6/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Gastrointestinal disorders Dyspepsia	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Gastrointestinal disorders Dysphagia	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Gastrointestinal disorders Flatulence	16.7% 7/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Gastrointestinal disorders Nausea	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
General disorders Fatigue	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
General disorders Oedema peripheral	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Infections and infestations Upper respiratory tract infection	16.7% 7/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Infections and infestations Urinary tract infection	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Injury, poisoning and procedural complications Fall	9.5% 4/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Metabolism and nutrition disorders Diabetes mellitus	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Musculoskeletal and connective tissue disorders Back pain	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Musculoskeletal and connective tissue disorders Muscular weakness	9.5% 4/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 4/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Nervous system disorders Headache	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)

Additional Information

Medical Information

Ultragenyx Pharmaceutical Inc

Phone: 1-888-756-8657

Email: medinfo@ultragenyx.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER