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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

Terminated Phase 2 Results posted Last updated 19 February 2019
What this trial tests

Phase 2 trial testing Aceneuramic Acid Extended-Release in Hereditary Inclusion Body Myopathy in 42 participants. Terminated before completion.

Timeline
29 April 2016
Primary endpoint
10 January 2018
10 January 2018

Quick facts

Lead sponsorUltragenyx Pharmaceutical Inc
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment42
Start date29 April 2016
Primary completion10 January 2018
Estimated completion10 January 2018
Sites5 locations across Canada, United States, Bulgaria

Drugs / interventions tested

Conditions studied

Sponsor

Ultragenyx Pharmaceutical Inc — full company profile →

Who can join

18 and older, any sex, with Hereditary Inclusion Body Myopathy or Distal Myopathy With Rimmed Vacuoles. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Primary · 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 defi

TEAEs
GroupValue95% CI
UX001 6g/Day30
Serious TEAEs
GroupValue95% CI
UX001 6g/Day1
TEAEs Causing Study Drug Discontinuation
GroupValue95% CI
UX001 6g/Day1
TEAEs Causing Study Discontinuation
GroupValue95% CI
UX001 6g/Day1
Number of Participants Taking Prior and Concomitant Medications Secondary · 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.

Prior Medications
GroupValue95% CI
UX001 6g/Day31
Concomitant Medications
GroupValue95% CI
UX001 6g/Day33
Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations Secondary · 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.

GroupValue95% CI
UX001 6g/Day0
Number of Participants With Clinically Significant Changes From Baseline In Vital Signs Secondary · 48 weeks

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

GroupValue95% CI
UX001 6g/Day0
Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results Secondary · 48 weeks

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

Hematology
GroupValue95% CI
UX001 6g/Day0
Clinical Chemistry
GroupValue95% CI
UX001 6g/Day2
Urinalysis
GroupValue95% CI
UX001 6g/Day0
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline Secondary · 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).

Overall Suicidal Behaviors: Baseline
GroupValue95% CI
UX001 6g/Day1
Overall Suicidal Behaviors: Post-Baseline
GroupValue95% CI
UX001 6g/Day0
Non-Suicide Self-Injurious Behavior: Baseline
GroupValue95% CI
UX001 6g/Day0
Non-Suicide Self-Injurious Behavior: Post-Baseline
GroupValue95% CI
UX001 6g/Day0
Completed Suicide: Post-Baseline
GroupValue95% CI
UX001 6g/Day0
Overall Suicidal Ideation: Baseline
GroupValue95% CI
UX001 6g/Day7
Overall Suicidal Ideation: Post-Baseline
GroupValue95% CI
UX001 6g/Day1
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time Secondary · 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.

Week 12
GroupValue95% CI
UX001 6g/Day0.16-0.33 – 0.64
Week 24
GroupValue95% CI
UX001 6g/Day-0.65-1.56 – 0.27
Week 36
GroupValue95% CI
UX001 6g/Day-0.69-1.57 – 0.18
Week 48
GroupValue95% CI
UX001 6g/Day-1.03-2.15 – 0.09
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time Secondary · 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.

Week 12
GroupValue95% CI
UX001 6g/Day0.57-0.05 – 1.19
Week 24
GroupValue95% CI
UX001 6g/Day-0.62-1.50 – 0.26
Week 36
GroupValue95% CI
UX001 6g/Day-0.51-1.58 – 0.55
Week 48
GroupValue95% CI
UX001 6g/Day-1.91-3.93 – 0.11
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time Secondary · 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.

Week 12
GroupValue95% CI
UX001 6g/Day-0.39-0.79 – 0.01
Week 24
GroupValue95% CI
UX001 6g/Day-0.71-1.43 – 0.01
Week 36
GroupValue95% CI
UX001 6g/Day-0.83-1.64 – -0.02
Week 48
GroupValue95% CI
UX001 6g/Day-0.40-1.78 – 0.98
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time Secondary · 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.

Week 12
GroupValue95% CI
UX001 6g/Day0.35-0.89 – 1.58
Week 24
GroupValue95% CI
UX001 6g/Day-1.95-3.87 – -0.03
Week 36
GroupValue95% CI
UX001 6g/Day-2.02-4.46 – 0.42
Week 48
GroupValue95% CI
UX001 6g/Day-3.34-6.90 – 0.22
Change From Baseline in HHD Raw Strength (Grip) Over Time Secondary · 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 th

Week 12
GroupValue95% CI
UX001 6g/Day0.258-0.103 – 0.620
Week 24
GroupValue95% CI
UX001 6g/Day0.128-0.377 – 0.632
Week 36
GroupValue95% CI
UX001 6g/Day0.038-0.724 – 0.799
Week 48
GroupValue95% CI
UX001 6g/Day-0.261-1.325 – 0.803
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time Secondary · 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 th

Week 12
GroupValue95% CI
UX001 6g/Day0.3390.085 – 0.592
Week 24
GroupValue95% CI
UX001 6g/Day0.379-0.228 – 0.987
Week 36
GroupValue95% CI
UX001 6g/Day0.4370.075 – 0.800
Week 48
GroupValue95% CI
UX001 6g/Day-0.277-0.698 – 0.144

Adverse events — posted to ClinicalTrials.gov

Time frame: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ace-ER 6 g/Day
Serious: 1/42 (2%)
Deaths: 0/42

Serious adverse events (3 terms)

ReactionSystemAce-ER 6 g/Day
PyelonephritisInfections and infestations
SepsisInfections and infestations
NephrolithiasisRenal and urinary disorders
Other adverse events (18 terms — click to expand)

ReactionSystemAce-ER 6 g/Day
Abdominal distensionGastrointestinal disorders
FlatulenceGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Abdominal pain upperGastrointestinal disorders
FallInjury, poisoning and procedural complications
Muscular weaknessMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DyspepsiaGastrointestinal disorders
DysphagiaGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Diabetes mellitusMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pyelonephritis, Sepsis, Nephrolithiasis.

Data from ClinicalTrials.gov NCT02731690 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges.
    Carrillo N, Malicdan MC, Huizing M. · · 2018 · cited 69× · PMID 30338442 · DOI 10.1007/s13311-018-0671-y
  2. CDG Therapies: From Bench to Bedside.
    Brasil S, Pascoal C, Francisco R, Marques-da-Silva D, et al · · 2018 · cited 66× · PMID 29702557 · DOI 10.3390/ijms19051304
  3. Phenotypic stratification and genotype-phenotype correlation in a heterogeneous, international cohort of GNE myopathy patients: First report from the GNE myopathy Disease Monitoring Program, registry portion.
    Pogoryelova O, Cammish P, Mansbach H, Argov Z, et al · · 2018 · cited 46× · PMID 29305133 · DOI 10.1016/j.nmd.2017.11.001
  4. GNE myopathy: from clinics and genetics to pathology and research strategies.
    Pogoryelova O, González Coraspe JA, Nikolenko N, Lochmüller H, et al · · 2018 · cited 38× · PMID 29720219 · DOI 10.1186/s13023-018-0802-x
  5. Patient reported outcomes in GNE myopathy: incorporating a valid assessment of physical function in a rare disease.
    Slota C, Bevans M, Yang L, Shrader J, et al · · 2018 · cited 10× · PMID 28637129 · DOI 10.1080/09638288.2017.1283712
  6. Decoding GNE Myopathy: From Molecular Basis to Therapeutic Advances.
    Yoshioka W, Noguchi S, Nishino I. · · 2025 · PMID 41082181 · DOI 10.4103/aian.aian_837_25

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