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: Acido Sialico - Sialic acid (INN: aceneuramic acid)
Product Code: UX001
Pharmaceutical Form: Prolonged-release tablet
Pharmaceutical form of the placebo: Prolonged-release tablet
Route o
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 childbearing potential who have not undergone a bilateral salpingooophorectomy 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 salpingooophorectomy 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 |
|---|---|
| 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;Secondary Objective: Key Secondary Objectives: Evaluate the effect of 6 g/day of SA-ER treatment of subjects with GNEM on: ¿ Lower extremity composite muscle strength score (LEC score) as measured by dynamometry ¿ 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 ;Primary end point(s): The primary clinical efficacy analysis will be the change from baseline in UEC score for the SA-ER group compared with placebo based on bilateral strength recorded in the following muscle groups using a dynamometer: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the muscle groups. Each muscle group value will represent the average of the right and left total values (measured in kg). The comparison of the two treatment groups will be based on the change from baseline in mean UEC score between SA-ER and placebo using GEE repeated measures analysis with baseline, gender, and geographic region as covariates. ;Timepoint(s) of evaluation of this end point: Baseline, Week 8, 16, 24, 32, 40, 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: the key secondary clinical efficacy analyses will assess the change from baseline for the SA-ER group compared with the placebo group using GEE for the following variables: ¿ LEC score based on a sum of the mean bilateral strength recorded in the following muscle groups: knee flexors, hip flexors, hip extensors, hip abductors and hip adductors ¿ Muscle strength in the knee extensors: bilateral total force (measured in kg) ¿ GNEM-FAS mobility domain score Other Secondary Endpoints: the analysis of other secondary endpoints will assess the change from baseline for the SA-ER group compared to the placebo group using GEE for the following variables: ¿ GNEM-FAS upper extremity domain score ¿ Sit-to-stand score calculated as the number of times a subject can rise from a sitting to a standing position in a 30-second period ¿ Weighted arm lift score calculated as the number of times a subject can raise a 1 kg weight overhead in a 30-second period ¿ Walking ability as measured by the 6MWT, which will be reported as distance in meters and percent predicted based on normative data for age and gender. ;Timepoint(s) of evaluation of this end point: Baseline, Week 8, 16, 24, 32, 40, 48 | — |
Countries
Bulgaria, Canada, France, Israel, Italy, United Kingdom, United States
Contacts
Public ContactClinical Operations
Ultragenyx Pharmaceutical Inc.
Outcome results
None listed