GNE Myopathy, also known as Hereditary Inclusion Body Myopathy (HIBM), Distal Myopathy with Rimmed Vacuoles (DMRV), Nonaka’s disease, or quadriceps sparing myopathy (QSM) MedDRA version: 20.0 Level: LLT Classification code 10075048 Term: Hereditary inclusion body myopathy System Organ Class: 100000004850
Conditions
Interventions
Product Name: Sialic acid (INN: aceneuramic acid)
Product Code: UX001
Pharmaceutical Form: Tablet
INN or Proposed INN: ACENEURAMIC ACID
CAS Number: 131-48-6
Concentration unit: mg milligram(s)
Concent
Sponsors
Ultragenyx Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female, aged 18 - 50 years, inclusive 2) 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 3) Have a documented diagnosis of GNEM, HIBM, DMRV, or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/MNK enzyme (genotyping will not be conducted in this study) 4) 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 5) Able to walk a minimum of 200 meters during the 6MWT at Screening without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (AFOs are permitted) 6) Willing and able to comply with all study procedures 7) 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 an 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) from the period following the signing of the informed consent through 3 months after last dose of study drug 8) 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 89 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) 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 2) History of more than 30 days treatment with SA-ER and/or SA-IR in prior clinical trials in the past year 3) 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 4) 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 5) Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study 6) 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 7) 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 8) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Key secondary objectives: Evaluate the effect of 6 g/day of SA-ER treatment of subjects with GNEM on: • Lower extremity muscle strength composite score (LEC score) as measured by dynamometry • Lower extremity muscle strength in the knee extensors as measured by dynamometry • Physical functioning as measured using the GNEM-FAS mobility domain score Other secondary objectives Evaluate the effect of 6 g/day of SA-ER treatment of subjects with GNEM on: • Physical functioning as measured using the GNEM-FAS upper extremity domain score • Lower extremity function as measured by a timed sit-to-stand test • Upper extremity function as measured by a timed weighted arm lift test • Lower extremity function as measured by distance walked in the 6MWT ;Main Objective: Evaluate the effect of 6 g/day SA-ER treatment of subjects with GNEM on upper extremity muscle strength (UEC score) as measured by dynamometry;Primary end point(s): Change from Baseline in Upper Extremity Composite Score ;Timepoint(s) of evaluation of this end point: Week 8, 16, 24, 32, 40, and 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints 1) Change from Baseline in lower extremity muscle strength composite score (LEC score) as measured by dynamometry 2) Change from Baseline in lower extremity muscle strength in the knee extensors as measured by dynamometry 3) Change from Baseline in Physical functioning as measured using the GNEM-FAS mobility domain score Other secondary endpoints 1) Change from Baseline in Physical functioning as measured using the GNEM-FAS upper extremity domain score 2) Change from Baseline in lower extremity function as measured by a timed sit-to-stand test 3) Change from Baseline in upper extremity function as measured by a timed weighted arm lift test 4) Change from Baseline in lower extremity function as measured by distance walked in the 6MWT;Timepoint(s) of evaluation of this end point: Week 8, 16, 24, 32, 40, and 48 | — |
Countries
Bulgaria, Canada, France, Israel, Italy, United Kingdom, United States
Contacts
Public ContactClinical Operations
Ultragenyx Pharmaceutical Inc.
Outcome results
None listed