Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Sialic Acid in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite [UEC] score) as measured by dynamometry.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Aceneuramic Acid Extended-Release (Ace-ER) Ace-ER 6 g/day, divided 3 times per day (TID) for 48 weeks. |
Drug: aceneuramic acid extended-release (Ace-ER)
tablets for oral use
Other Names:
|
| Placebo Comparator: Placebo Matching placebo TID for 48 weeks. |
Drug: Placebo
tablets for oral use
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in UEC Score (Total Force in kg) at Week 48 [Baseline, Week 48]
Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg).
Secondary Outcome Measures
- Change From Baseline in Muscle Strength in the Knee Extensors at Week 48 [Baseline, Week 48]
Lower extremity muscle strength in the knee extensors was measured by dynamometry. Bilateral total force was defined as the average of the right and left force values (measured in kg).
- Change From Baseline in LEC Score (Total Force in kg) at Week 48 [Baseline, Week 48]
Muscle strength based on MVIC against a dynamometer was measured bilaterally in the following lower extremity muscle groups: knee flexors, hip flexors, hip extensors, hip abductors and hip adductors. The LEC is derived from the sum of the average of the right and left total force values (measured in kg).
- Change From Baseline in GNEM FAS Mobility Domain Score at Week 48 [Baseline, Week 48]
Lower extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the lower extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
- Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48 [Baseline, Week 48]
Upper extremity function was assessed using a weighted arm lift test performed bilaterally. The number of times the participant can raise a 1 kg weight above the head in a 30-second period was recorded.
- Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48 [Baseline, Week 48]
Lower extremity function was assessed using a sit-to-stand test. The number of times the participant can rise from a seated to a standing position in a 30-second period was recorded.
- Change From Baseline in Meters Walked in the 6MWT at Week 48 [Baseline, Week 48]
The total distance walked (meters) in a 6-minute period was measured.
- Change From Baseline in Percent Predicted Meters Walked in the 6MWT at Week 48 [Baseline, Week 48]
The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated.
- Change From Baseline in GNEM FAS Upper Extremity Domain Score at Week 48 [Baseline, Week 48]
Upper extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the upper extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female, aged 18 to 55 years, inclusive
-
Willing and able to provide written, signed informed consent after the nature of the study has been explained, and before any research-related procedures are conducted
-
Have a documented diagnosis of GNEM, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/N-acetylmannosamine kinase (MNK) enzyme (genotyping will not be conducted in this study)
-
Able to provide reproducible force in elbow flexors (i.e. two dynamometry force values with no more than 15% variability in the dominant arm) at Screening
-
Able to walk a minimum of 200 meters during the six-meter walk test (6MWT) at Screening without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (ankle foot orthosis/orthoses are permitted)
-
Willing and able to comply with all study procedures
-
Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use a highly effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence [when this is in line with the preferred and usual lifestyle of the subject], which means not having sex because the subject chooses not to), from the period following the signing of the informed consent through 3 months after last dose of study drug
-
Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause for at least two years, have had tubal ligation at least one year prior to Screening, or who have had a total hysterectomy or bilateral salpingo-oophorectomy
Exclusion Criteria:
-
Ingestion of N-acetyl-D-mannosamine (ManNAc), sialic acid (SA), or related metabolites; intravenous immunoglobulin (IVIG); or anything that can be metabolized to produce SA in the body within 60 days prior to the Screening Visit
-
History of more than 30 days treatment with SA-ER and/or Sialic Acid Immediate Release (SA-IR) in prior clinical trials in the past year
-
Has had any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
-
Has serum transaminase (i.e. aspartate aminotransferase [AST] or gamma-glutamyl transpeptidase [GGT]) levels greater than 3X the upper limit of normal (ULN) for age/gender, or serum creatinine of greater than 2X ULN at Screening
-
Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study
-
Use of any investigational product or investigational medical device within 30 days prior to Screening, or anticipated requirement for any investigational agent prior to completion of all scheduled study assessments
-
Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe participation in the study
-
Has a concurrent disease, active suicidal ideation, or other condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, Irvine | Irvine | California | United States | 92697 |
| 2 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 3 | New York University School of Medicine | New York | New York | United States | 10016 |
| 4 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 5 | UMHAT "Alexandrovska" | Sofia | Bulgaria | ||
| 6 | McMaster University | Hamilton | Ontario | Canada | L8N3Z5 |
| 7 | CHU La Réunion - site GHSR | Saint-Pierre | Reunion | France | |
| 8 | Institut de Myologie GH Pitié-Salpêtrière | Paris | France | ||
| 9 | Hadassah-Hebrew University Medical Center | Jerusalem | Israel | ||
| 10 | University of Messina | Messina | Italy | ||
| 11 | University of Milan | Milan | Italy | ||
| 12 | Università Cattolica | Rome | Italy | ||
| 13 | The Newcastle upon Tyne Hospitals | Newcastle Upon Tyne | Tyne And Wear | United Kingdom | NE1 4LP |
Sponsors and Collaborators
- Ultragenyx Pharmaceutical Inc
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- UX001-CL301
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Aceneuramic acid extended-release (Ace-ER) 6 g/day, divided 3 times per day (TID) for 48 weeks. | Matching placebo TID for 48 weeks. |
| Period Title: Overall Study | ||
| STARTED | 45 | 44 |
| COMPLETED | 44 | 43 |
| NOT COMPLETED | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Ace-ER 6 g/Day | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. | Total of all reporting groups |
| Overall Participants | 45 | 43 | 88 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
33.8
(7.91)
|
36.2
(8.59)
|
35.0
(8.29)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
20
44.4%
|
20
46.5%
|
40
45.5%
|
| Male |
25
55.6%
|
23
53.5%
|
48
54.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
5
11.1%
|
7
16.3%
|
12
13.6%
|
| Not Hispanic or Latino |
39
86.7%
|
33
76.7%
|
72
81.8%
|
| Unknown or Not Reported |
1
2.2%
|
3
7%
|
4
4.5%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
6
13.3%
|
7
16.3%
|
13
14.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
36
80%
|
32
74.4%
|
68
77.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
3
6.7%
|
4
9.3%
|
7
8%
|
| Upper Extremity Composite (UEC) Score (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
55.99
(26.950)
|
56.31
(29.287)
|
56.14
(27.954)
|
| Muscle Strength in the Knee Extensors (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
26.53
(9.035)
|
26.65
(8.969)
|
26.59
(8.951)
|
| Lower Extremity Composite (LEC) Score (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
53.52
(33.751)
|
55.17
(39.324)
|
54.33
(36.378)
|
| Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
26.38
(7.581)
|
26.23
(6.403)
|
26.31
(6.990)
|
| Stands in Sit-to-Stand Test (stands) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [stands] |
12.38
(4.103)
|
12.58
(4.316)
|
12.48
(4.185)
|
| Lifts in Weighted Arm Lift Test (arm lifts) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [arm lifts] |
30.50
(10.452)
|
28.18
(9.824)
|
29.33
(10.137)
|
| Distance Walked in 6-Minute Walk Test (6MWT) (meters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [meters] |
367.0
(115.07)
|
361.2
(109.87)
|
364.2
(111.95)
|
| Percent of Predicted Distance Walked in 6MWT (percentage of predicted meters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [percentage of predicted meters] |
49.97
(15.521)
|
49.87
(14.823)
|
49.92
(15.097)
|
Outcome Measures
| Title | Change From Baseline in UEC Score (Total Force in kg) at Week 48 |
|---|---|
| Description | Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg). |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [kg] |
-2.25
|
-2.99
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5387 |
| Comments | Generalized estimating equation (GEE) model includes change from Baseline (BL) as dependent variable, visit, treatment and visit by treatment as fixed factors, and BL values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% -1.61 to 3.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Ace-ER - placebo | |
| Title | Change From Baseline in Muscle Strength in the Knee Extensors at Week 48 |
|---|---|
| Description | Lower extremity muscle strength in the knee extensors was measured by dynamometry. Bilateral total force was defined as the average of the right and left force values (measured in kg). |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [kg] |
0.05
|
0.45
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6938 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -2.38 to 1.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Ace-ER - placebo | |
| Title | Change From Baseline in LEC Score (Total Force in kg) at Week 48 |
|---|---|
| Description | Muscle strength based on MVIC against a dynamometer was measured bilaterally in the following lower extremity muscle groups: knee flexors, hip flexors, hip extensors, hip abductors and hip adductors. The LEC is derived from the sum of the average of the right and left total force values (measured in kg). |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [kg] |
-1.92
|
-0.44
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5023 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.49 | |
| Confidence Interval |
(2-Sided) 95% -5.83 to 2.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Ace-ER - placebo | |
| Title | Change From Baseline in GNEM FAS Mobility Domain Score at Week 48 |
|---|---|
| Description | Lower extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the lower extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-2.49
|
-1.77
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2739 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.72 | |
| Confidence Interval |
(2-Sided) 95% -2.01 to 0.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Ace-ER - placebo | |
| Title | Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48 |
|---|---|
| Description | Upper extremity function was assessed using a weighted arm lift test performed bilaterally. The number of times the participant can raise a 1 kg weight above the head in a 30-second period was recorded. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [arm lifts] |
0.03
|
2.79
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1235 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.76 | |
| Confidence Interval |
(2-Sided) 95% -6.27 to 0.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference: Ace-ER 6 g/day - placebo | |
| Title | Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48 |
|---|---|
| Description | Lower extremity function was assessed using a sit-to-stand test. The number of times the participant can rise from a seated to a standing position in a 30-second period was recorded. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [stands] |
0.11
|
0.53
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3907 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.43 | |
| Confidence Interval |
(2-Sided) 95% -1.40 to 0.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference: Ace-ER 6 g/day - placebo | |
| Title | Change From Baseline in Meters Walked in the 6MWT at Week 48 |
|---|---|
| Description | The total distance walked (meters) in a 6-minute period was measured. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [meters] |
-17.79
|
-6.81
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1964 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -10.98 | |
| Confidence Interval |
(2-Sided) 95% -27.64 to 5.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference: Ace-ER 6 g/day - placebo | |
| Title | Change From Baseline in Percent Predicted Meters Walked in the 6MWT at Week 48 |
|---|---|
| Description | The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [percentage of predicted meters] |
-2.37
|
-0.97
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2241 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.40 | |
| Confidence Interval |
(2-Sided) 95% -3.66 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference: Ace-ER - placebo | |
| Title | Change From Baseline in GNEM FAS Upper Extremity Domain Score at Week 48 |
|---|---|
| Description | Upper extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the upper extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Primary Analysis Set: participants who had a Baseline and at least 1 postbaseline measurement. |
| Arm/Group Title | Ace-ER 6 g/Day | Placebo |
|---|---|---|
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. |
| Measure Participants | 45 | 43 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-1.40
|
-1.08
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ace-ER 6 g/Day, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5608 |
| Comments | GEE model includes change from Baseline as dependent variable, visit, treatment and visit by treatment as fixed factors, and Baseline values, sex, and region as covariates, with compound symmetry covariance structure. | |
| Method | GEE model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.32 | |
| Confidence Interval |
(2-Sided) 95% -1.39 to 0.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference: Ace-ER 6 g/day - placebo | |
Adverse Events
| Time Frame | Screening through Week 48 plus 28 days (+5 days). The mean (SD) duration of treatment was 340.2 (12.02) days and 332.9 (40.86) days for the Ace-ER and placebo groups, respectively. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Ace-ER 6 g/Day | Placebo | ||
| Arm/Group Description | Ace-ER 6 g/day, divided TID for 48 weeks. | Matching placebo TID for 48 weeks. | ||
All Cause Mortality |
||||
| Ace-ER 6 g/Day | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/45 (0%) | 0/44 (0%) | ||
Serious Adverse Events |
||||
| Ace-ER 6 g/Day | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/45 (4.4%) | 1/44 (2.3%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/45 (2.2%) | 0/44 (0%) | ||
| Gastrointestinal disorders | ||||
| Gastritis | 1/45 (2.2%) | 0/44 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion | 0/45 (0%) | 1/44 (2.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Ace-ER 6 g/Day | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/45 (84.4%) | 30/44 (68.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 4/45 (8.9%) | 4/44 (9.1%) | ||
| Abdominal pain upper | 10/45 (22.2%) | 3/44 (6.8%) | ||
| Diarrhoea | 8/45 (17.8%) | 6/44 (13.6%) | ||
| Flatulence | 6/45 (13.3%) | 5/44 (11.4%) | ||
| Frequent bowel movements | 3/45 (6.7%) | 0/44 (0%) | ||
| Nausea | 5/45 (11.1%) | 2/44 (4.5%) | ||
| General disorders | ||||
| Asthenia | 2/45 (4.4%) | 3/44 (6.8%) | ||
| Fatigue | 4/45 (8.9%) | 4/44 (9.1%) | ||
| Influenza like illness | 4/45 (8.9%) | 11/44 (25%) | ||
| Pain | 1/45 (2.2%) | 3/44 (6.8%) | ||
| Infections and infestations | ||||
| Influenza | 1/45 (2.2%) | 4/44 (9.1%) | ||
| Upper respiratory tract infection | 5/45 (11.1%) | 1/44 (2.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 4/45 (8.9%) | 0/44 (0%) | ||
| Fall | 7/45 (15.6%) | 7/44 (15.9%) | ||
| Skin abrasion | 0/45 (0%) | 3/44 (6.8%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 4/45 (8.9%) | 2/44 (4.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/45 (20%) | 5/44 (11.4%) | ||
| Back pain | 5/45 (11.1%) | 4/44 (9.1%) | ||
| Muscular weakness | 6/45 (13.3%) | 3/44 (6.8%) | ||
| Musculoskeletal pain | 4/45 (8.9%) | 2/44 (4.5%) | ||
| Myalgia | 6/45 (13.3%) | 1/44 (2.3%) | ||
| Pain in extremity | 4/45 (8.9%) | 3/44 (6.8%) | ||
| Nervous system disorders | ||||
| Dizziness | 3/45 (6.7%) | 1/44 (2.3%) | ||
| Dysgeusia | 3/45 (6.7%) | 0/44 (0%) | ||
| Headache | 7/45 (15.6%) | 7/44 (15.9%) | ||
| Sciatica | 0/45 (0%) | 3/44 (6.8%) | ||
| Psychiatric disorders | ||||
| Sleep disorder | 0/45 (0%) | 4/44 (9.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/45 (11.1%) | 4/44 (9.1%) | ||
| Nasal congestion | 4/45 (8.9%) | 1/44 (2.3%) | ||
| Oropharyngeal pain | 4/45 (8.9%) | 2/44 (4.5%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Medical Information |
|---|---|
| Organization | Ultragenyx Pharmaceutical Inc |
| Phone | 1-888-756-8567 |
| medinfo@ultragenyx.com |
- UX001-CL301