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Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Sialic Acid in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM) (GNEM)

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ClinicalTrials.gov Identifier: NCT02377921
Recruitment Status : Completed
First Posted : March 4, 2015
Results First Posted : July 9, 2018
Last Update Posted : June 27, 2019
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Tracking Information
First Submitted Date  ICMJE February 27, 2015
First Posted Date  ICMJE March 4, 2015
Results First Submitted Date  ICMJE June 7, 2018
Results First Posted Date  ICMJE July 9, 2018
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE May 20, 2015
Actual Primary Completion Date June 9, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2018)
Change From Baseline in UEC Score (Total Force in kg) at Week 48 [ Time Frame: Baseline, Week 48 ]
Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg).
Original Primary Outcome Measures  ICMJE
 (submitted: March 3, 2015)
Upper Extremity Muscle Strength [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
Upper extremity muscle strength will be measured by dynamometry
Change History Complete list of historical versions of study NCT02377921 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2018)
  • Change From Baseline in Muscle Strength in the Knee Extensors at Week 48 [ Time Frame: Baseline, Week 48 ]
    Lower extremity muscle strength in the knee extensors was measured by dynamometry. Bilateral total force was defined as the average of the right and left force values (measured in kg).
  • Change From Baseline in LEC Score (Total Force in kg) at Week 48 [ Time Frame: Baseline, Week 48 ]
    Muscle strength based on MVIC against a dynamometer was measured bilaterally in the following lower extremity muscle groups: knee flexors, hip flexors, hip extensors, hip abductors and hip adductors. The LEC is derived from the sum of the average of the right and left total force values (measured in kg).
  • Change From Baseline in GNEM FAS Mobility Domain Score at Week 48 [ Time Frame: Baseline, Week 48 ]
    Lower extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the lower extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
  • Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48 [ Time Frame: Baseline, Week 48 ]
    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.
  • Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48 [ Time Frame: Baseline, Week 48 ]
    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.
  • Change From Baseline in Meters Walked in the 6MWT at Week 48 [ Time Frame: Baseline, Week 48 ]
    The total distance walked (meters) in a 6-minute period was measured.
  • Change From Baseline in Percent Predicted Meters Walked in the 6MWT at Week 48 [ Time Frame: Baseline, Week 48 ]
    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.
  • Change From Baseline in GNEM FAS Upper Extremity Domain Score at Week 48 [ Time Frame: Baseline, Week 48 ]
    Upper extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the upper extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2015)
  • GNEM-FAS Mobility Domain Score [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
  • GNEM-FAS Upper Extremity Domain Score [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
  • Lower Extremity Muscle Strength [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
    Lower extremity muscle strength will be measured by dynamometry
  • Timed Sit-to-Stand Test [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
  • Timed Weighted Arm Lift Test [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
  • Lower Extremity Muscle Strength in the Knee Extensors [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
    Lower extremity muscle strength in the knee extensors will be measured by dynamometry
  • Distance Walked in the Six-minute Walk Test [ Time Frame: Change from Baseline at Weeks 8, 16, 24, 32, 40, and 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Sialic Acid in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Official Title  ICMJE A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended-Release Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
Brief Summary The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite [UEC] score) as measured by dynamometry.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hereditary Inclusion Body Myopathy
  • Distal Myopathy With Rimmed Vacuoles
  • Distal Myopathy, Nonaka Type
  • GNE Myopathy
Intervention  ICMJE
  • Drug: aceneuramic acid extended-release (Ace-ER)
    tablets for oral use
    Other Names:
    • UX001
    • sialic acid extended-release (SA-ER)
  • Drug: Placebo
    tablets for oral use
Study Arms  ICMJE
  • Experimental: Aceneuramic Acid Extended-Release (Ace-ER)
    Ace-ER 6 g/day, divided 3 times per day (TID) for 48 weeks.
    Intervention: Drug: aceneuramic acid extended-release (Ace-ER)
  • Placebo Comparator: Placebo
    Matching placebo TID for 48 weeks.
    Intervention: Drug: Placebo
Publications * Lochmüller H, Behin A, Caraco Y, Lau H, Mirabella M, Tournev I, Tarnopolsky M, Pogoryelova O, Woods C, Lai A, Shah J, Koutsoukos T, Skrinar A, Mansbach H, Kakkis E, Mozaffar T. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy. Neurology. 2019 Apr 30;92(18):e2109-e2117. doi: 10.1212/WNL.0000000000006932. Epub 2019 Jan 25.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: August 9, 2017)
89
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2015)
80
Actual Study Completion Date  ICMJE June 9, 2017
Actual Primary Completion Date June 9, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female, aged 18 to 55 years, inclusive
  • 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)
  • Able to provide reproducible force in elbow flexors (i.e. two dynamometry force values with no more than 15% variability in the dominant arm) at Screening
  • Able to walk a minimum of 200 meters during the six-meter walk test (6MWT) at Screening without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (ankle foot orthosis/orthoses are permitted)
  • 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 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 3 months 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), sialic acid (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
  • History of more than 30 days treatment with SA-ER and/or Sialic Acid Immediate Release (SA-IR) in prior clinical trials in the past year
  • Has had any hypersensitivity to SA 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 to 55 Years   (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,   France,   Israel,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02377921
Other Study ID Numbers  ICMJE UX001-CL301
Has Data Monitoring Committee Yes
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 Not Provided
PRS Account Ultragenyx Pharmaceutical Inc
Verification Date June 2019

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