Back to resultsStudy to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Primary Purpose
Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aceneuramic Acid Extended-Release Tablets
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Inclusion Body Myopathy focused on measuring GNE Myopathy, GNEM, Nonaka, Hereditary Inclusion Body Myopathy, HIBM, DMRV, QSM
Eligibility Criteria
Inclusion Criteria:
- Have completed UX001-CL202, UX001-CL301 or UX001-CL203 study
- 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
- Willing to comply with all study procedures
- Female participants of child-bearing potential or male participants with female 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 30 days 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:
Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
- Ingestion of N-acetyl-D-mannosamine (ManNAc) 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
- Has had any hypersensitivity to sialic acid (SA) or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
- 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
Sites / Locations
- UCLA
- University of California, Irvine
- Washington University School of Medicine, St. Louis
- New York University School of Medicine
- Icahn School of Medicine at Mount Sinai
- UMHAT Alexandrovska, Bulgaria
- McMaster University
- CHU La Réunion - site GHSR
- Institut de Myologie GH Pitié-Salpêtrière
- Hadassah-Hebrew University Medical Center
- University of Messina
- University of Milan
- Università Cattolica
- The Newcastle upon Tyne Hospitals
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Drug: Aceneuramic Acid Extended-Release Tablets
Arm Description
Participants will take 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day (TID).
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
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. The severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death.
Change From Baseline in HHD UEC Score Over Time
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. The UEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the baseline value as a covariate.
Secondary Outcome Measures
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
GNEM-FAS Expanded Version Mobility subscale score has 13 items and ranges from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
GNEM-FAS Expanded Version Upper Extremity subscale score has 9 items and ranges 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 baseline value as a covariate.
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
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. The LEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in Meters Walked in 6MWT Over Time
The total distance walked (meters) in a 6-minute period was measured. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
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. Predicted 6MWT distance (meters) = 868.8 - (2.99 x Age) - (74.7 x Sex), where age is baseline age in years, and sex = 0 for males, and 1 for females. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in Total Force in Knee Extensors Over Time
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. Bilateral total force was defined as the average of the right and left force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
The percent predicted total force value of lower extremity muscle strength in the knee extensors was determined based on reference equations adjusting for age, gender, height, and weight. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Full Information
NCT ID
NCT02736188
First Posted
April 4, 2016
Last Updated
March 22, 2023
Sponsor
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT02736188
Brief Title
Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Official Title
Phase 3B Open-Label Extension Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Study Start Date
May 2, 2016 (Actual)
Primary Completion Date
January 10, 2018 (Actual)
Study Completion Date
January 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to evaluate the long-term safety and efficacy of Ace-ER treatment in subjects with GNEM.
Detailed Description
This Phase 3b extension study will assess the long-term safety of Ace-ER in patients who participated in and completed study UX001-CL301 (NCT02377921), study UX001-CL202 (NCT01830972), and study UX001-CL203 (NCT02731690).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type, GNE Myopathy, Quadriceps Sparing Myopathy
Keywords
GNE Myopathy, GNEM, Nonaka, Hereditary Inclusion Body Myopathy, HIBM, DMRV, QSM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
143 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Drug: Aceneuramic Acid Extended-Release Tablets
Arm Type
Experimental
Arm Description
Participants will take 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day (TID).
Intervention Type
Drug
Intervention Name(s)
Aceneuramic Acid Extended-Release Tablets
Other Intervention Name(s)
UX001, Sialic Acid Extended Release, Ace-ER
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
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. The severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death.
Time Frame
From first dose of study drug through the end of treatment plus 30 days (+5 days). Mean (SD) duration of treatment was 256.3 (101.54) days.
Title
Change From Baseline in HHD UEC Score Over Time
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. The UEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, 48
Secondary Outcome Measure Information:
Title
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Description
GNEM-FAS Expanded Version Mobility subscale score has 13 items and ranges from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, 48
Title
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Description
GNEM-FAS Expanded Version Upper Extremity subscale score has 9 items and ranges 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 baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, 48
Title
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
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. The LEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in Meters Walked in 6MWT Over Time
Description
The total distance walked (meters) in a 6-minute period was measured. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
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. Predicted 6MWT distance (meters) = 868.8 - (2.99 x Age) - (74.7 x Sex), where age is baseline age in years, and sex = 0 for males, and 1 for females. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in Total Force in Knee Extensors Over Time
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. Bilateral total force was defined as the average of the right and left force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
Title
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Description
The percent predicted total force value of lower extremity muscle strength in the knee extensors was determined based on reference equations adjusting for age, gender, height, and weight. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame
Baseline, Weeks 8, 16, 24, and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have completed UX001-CL202, UX001-CL301 or UX001-CL203 study
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
Willing to comply with all study procedures
Female participants of child-bearing potential or male participants with female 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 30 days 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:
Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
Ingestion of N-acetyl-D-mannosamine (ManNAc) 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
Has had any hypersensitivity to sialic acid (SA) or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Washington University School of Medicine, St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
UMHAT Alexandrovska, Bulgaria
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
CHU La Réunion - site GHSR
City
Saint-Pierre
State/Province
Reunion
Country
France
Facility Name
Institut de Myologie GH Pitié-Salpêtrière
City
Paris
Country
France
Facility Name
Hadassah-Hebrew University Medical Center
City
Jerusalem
Country
Israel
Facility Name
University of Messina
City
Messina
Country
Italy
Facility Name
University of Milan
City
Milan
Country
Italy
Facility Name
Università Cattolica
City
Rome
Country
Italy
Facility Name
The Newcastle upon Tyne Hospitals
City
Newcastle Upon Tyne
State/Province
Tyne And Wear
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
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