- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02731690
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
February 13, 2019 updated by: Ultragenyx Pharmaceutical Inc
A Phase 2 Open-label Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER) Tablets in GNE Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy (HIBM)) Patients With Severe Ambulatory Impairment
The primary objective of this Phase 2 study is to evaluate the safety of open-label 6 g/day Ace-ER in GNEM participants with severe ambulatory impairment.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
42
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Sofia, Bulgaria, 1431
- University Alexandrovska, Bulgaria
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Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
- McMaster University
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California
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Orange, California, United States, 92868
- University of California, Irvine
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University, St. Louis
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New York
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New York, New York, United States, 10016
- NYU Langone Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female, aged ≥ 18 years old
- 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).
Should meet the criteria for severe ambulatory impairment defined below:
- Unable to rise from a seated position to standing without help from another person, assistive device(s), stationary object, or other support AND
- Unable to walk without the assistance of another person OR if able to walk (use of assistive device(s) permitted), requires at least 2 minutes to walk 40 meters (one full lap of the 6-minute walk test [6MWT] course) AND
- Use of wheelchair or scooter for activities outside of the home or unable to leave the home independently
- 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 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:
- Ingestion of N-acetyl-D-mannosamine (ManNAc), 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
- Prior participation in a clinical trial involving treatment with Ace-ER/placebo and/or Sialic Acid immediate release (SA-IR) in the past year
- Has had any hypersensitivity to aceneuramic acid 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Open Label UX001, 6g/day
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oral tablets
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Time Frame: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
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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.
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48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants Taking Prior and Concomitant Medications
Time Frame: 48 weeks
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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.
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48 weeks
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Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations
Time Frame: 48 weeks
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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.
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48 weeks
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Number of Participants With Clinically Significant Changes From Baseline In Vital Signs
Time Frame: 48 weeks
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Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature.
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48 weeks
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Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results
Time Frame: 48 weeks
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The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis.
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48 weeks
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Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline
Time Frame: 48 weeks
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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).
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48 weeks
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Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in HHD Raw Strength (Grip) Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Change From Baseline in HHD Raw Strength (Key Pinch) Over Time
Time Frame: Baseline, Weeks 12, 24, 36, and 48
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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.
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Baseline, Weeks 12, 24, 36, and 48
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 29, 2016
Primary Completion (Actual)
January 10, 2018
Study Completion (Actual)
January 10, 2018
Study Registration Dates
First Submitted
March 24, 2016
First Submitted That Met QC Criteria
April 6, 2016
First Posted (Estimate)
April 7, 2016
Study Record Updates
Last Update Posted (Actual)
February 19, 2019
Last Update Submitted That Met QC Criteria
February 13, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UX001-CL203
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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