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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02731690
Recruitment Status : Terminated
First Posted : April 7, 2016
Last Update Posted : November 14, 2018
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

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.

Condition or disease Intervention/treatment Phase
Hereditary Inclusion Body Myopathy Distal Myopathy With Rimmed Vacuoles Distal Myopathy, Nonaka Type GNE Myopathy Quadriceps Sparing Myopathy Inclusion Body Myopathy 2 Drug: Aceneuramic Acid Extended-Release Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 29, 2016
Actual Primary Completion Date : January 10, 2018
Actual Study Completion Date : January 10, 2018

Arm Intervention/treatment
Experimental: Open Label UX001, 6g/day Drug: Aceneuramic Acid Extended-Release
oral tablets
Other Names:
  • Ace-ER
  • Sialic Acid Extended Release
  • UX001

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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 ]
  2. Change in muscle strength in the upper extremity as measured by dynamometry over the duration of study [ Time Frame: 48 Weeks ]
  3. Change in lower extremity muscle strength in the knee extensors as measured by dynamometry over the duration of the study [ Time Frame: 48 Weeks ]

Other Outcome Measures:
  1. 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 ]
  2. 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 ]
  3. Changes in serum creatine kinase (CK) as a marker of muscle injury over the duration of the study [ Time Frame: 48 Weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02731690

United States, California
University of California, Irvine
Orange, California, United States, 92868
United States, Missouri
Washington University, St. Louis
Saint Louis, Missouri, United States, 63110
United States, New York
NYU Langone Medical Center
New York, New York, United States, 10016
University Alexandrovska, Bulgaria
Sofia, Bulgaria, 1431
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8N 3Z5
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Study Director: Medical Director Ultragenyx Pharmaceutical Inc

Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT02731690     History of Changes
Other Study ID Numbers: UX001-CL203
First Posted: April 7, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Keywords provided by Ultragenyx Pharmaceutical Inc:
GNE Myopathy
Hereditary Inclusion Body Myopathy

Additional relevant MeSH terms:
Muscular Diseases
Distal Myopathies
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Muscular Dystrophies
Muscular Disorders, Atrophic
Genetic Diseases, Inborn