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

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

Tracking Information
First Submitted Date  ICMJE March 24, 2016
First Posted Date  ICMJE April 7, 2016
Results First Submitted Date  ICMJE January 7, 2019
Results First Posted Date  ICMJE February 19, 2019
Last Update Posted Date February 19, 2019
Actual Study Start Date  ICMJE April 29, 2016
Actual Primary Completion Date January 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
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) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2016)
Evaluate the safety of Ace-ER in GNEM subjects with severe ambulatory impairment (frequency of adverse events (AEs) and serious adverse events (SAEs)) [ Time Frame: 48 Weeks ]
The primary endpoint of the study is the incidence and frequency of adverse events (AEs) and serious adverse events (SAEs) assessed as related to Ace-ER over the duration of the study.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
  • Number of Participants Taking Prior and Concomitant Medications [ Time Frame: 48 weeks ]
    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.
  • Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations [ Time Frame: 48 weeks ]
    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.
  • Number of Participants With Clinically Significant Changes From Baseline In Vital Signs [ Time Frame: 48 weeks ]
    Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature.
  • Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results [ Time Frame: 48 weeks ]
    The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis.
  • Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline [ Time Frame: 48 weeks ]
    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).
  • Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in HHD Raw Strength (Grip) Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
  • Change From Baseline in HHD Raw Strength (Key Pinch) Over Time [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2016)
  • Change in GNEM-FAS(GNE Myopathy Functional Activities Scale) Expanded Version scores (including domain scores) from baseline over the duration of the study [ Time Frame: 48 Weeks ]
  • Change in muscle strength in the upper extremity as measured by dynamometry over the duration of study [ Time Frame: 48 Weeks ]
  • Change in lower extremity muscle strength in the knee extensors as measured by dynamometry over the duration of the study [ Time Frame: 48 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 6, 2016)
  • Change in health-related quality of life as assessed by using Short Form Health Survey -36 (SF-36) over the duration of the study [ Time Frame: 48 Weeks ]
  • Change in symptom severity as measured by the Patient Global Impression of Change (PGI-C) over the duration of the study [ Time Frame: 48 Weeks ]
  • Changes in serum creatine kinase (CK) as a marker of muscle injury over the duration of the study [ Time Frame: 48 Weeks ]
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hereditary Inclusion Body Myopathy
  • Distal Myopathy With Rimmed Vacuoles
  • Distal Myopathy, Nonaka Type
  • GNE Myopathy
  • Quadriceps Sparing Myopathy
  • Inclusion Body Myopathy 2
Intervention  ICMJE Drug: Aceneuramic Acid Extended-Release
oral tablets
Other Names:
  • Ace-ER
  • Sialic Acid Extended Release
  • UX001
Study Arms  ICMJE Experimental: Open Label UX001, 6g/day
Intervention: Drug: Aceneuramic Acid Extended-Release
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 12, 2018)
42
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2016)
30
Actual Study Completion Date  ICMJE January 10, 2018
Actual Primary Completion Date January 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02731690
Other Study ID Numbers  ICMJE UX001-CL203
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ultragenyx Pharmaceutical Inc
Study Sponsor  ICMJE Ultragenyx Pharmaceutical Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Ultragenyx Pharmaceutical Inc
PRS Account Ultragenyx Pharmaceutical Inc
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP