GNE Myopathy
Conditions
Keywords
GNEM, Hereditary Inclusion Body Myopathy (HIBM), Distal Myopathy with Rimmed Vacuoles (DMRV), Inclusion Body Myopathy 2 (IBM2), Nonaka Myopathy
Brief summary
The goal of this study is to assess the safety and dose of UX016 and its impact on muscle strength in adults with GNE Myopathy (GNEM).
Interventions
DRUGUX016
Tablets for oral use
OTHERPlacebo
Tablets for oral use. Tablets will match the UX016 tablets, but contain no active ingredients
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* A confirmed diagnosis of GNEM (also known as distal myopathy with rimmed vacuoles \[DMRV\], hereditary inclusion body myopathy \[HIBM\], inclusion body myopathy 2 \[IBM2\], and Nonaka myopathy in Japan) by Clinical Laboratory Improvement Amendments (CLIA)-certified genetic testing with identification of a disease-associated variant in the gene encoding the GNE/MNK enzyme. Genotyping will not be conducted in this protocol * Ability to walk a minimum of 20 m independently during Screening. The use of assistive devices and orthotics is allowed. * Has ≤ 80% of normal biceps strength (dominant side) assessed by hand-held dynamometry (HHD) associated with a clinical pattern of weakening in the upper extremity and ability to provide reproducible force in unilateral elbow flexors (dominant side) during HHD testing (unilateral between test variability of ≤ 15%) during Screening. * Willing and able to comply with all study procedures including needle muscle biopsies of the quadriceps muscle. * From informed consent to after the last dose of study drug, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant and willing to have additional pregnancy testing during the study. Females considered not of childbearing potential include those who have been in menopause for at least 2 years, have had tubal ligation at least 1 year prior to Screening, or who have had a total hysterectomy. If male, agree not to father a child or donate sperm. * Provide informed consent after the nature of the study has been explained and prior to any research-related procedures.
Exclusion criteria
* Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites, including 6-sialyllactose; intravenous immune globulin; supplements; or anything that can be metabolized to produce significant amounts of SA in the body for the prior 60 days through the end of the study. * Any changes in diet or exercise routine in the prior 30 days. Subjects are strongly discouraged from making any changes to their diet and exercise routines following enrollment. * Receiving concomitant oral medications that are substrates for CYP2B6, P-glycoprotein (P-gp) transporters, or breast cancer resistance protein (BCRP) transporters. * Known hypersensitivity to SA or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects. * Any of the following laboratory abnormalities at Screening: * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or glutamate dehydrogenase (GLDH) \> 3 × upper limit of normal (ULN) * Total bilirubin \> 2 × ULN * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 based on cystatin C. * Men with a Fridericia-corrected QT interval (QTcF) \> 450 msec and women with a QTcF \> 460 msec at Screening. * Presence or history of any condition, laboratory abnormality, or infection that, in the Investigator's judgment, would interfere with participation, pose undue safety risk, or confound interpretation of study results. * 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 requirement for any investigational agent prior to completion of all scheduled study assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | Up to Week 96 (Double Blind and Extension Periods) |
| Upper Extremity Composite (UEC) Score Change From Baseline | Baseline, 48 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Area Under the Curve (AUC) of UX016 and Free Sialic Acid (SA) | Baseline, 12 Weeks |
| Plasma Maximum Concentration (Cmax) of UX016 and SA | Baseline, 12 Weeks |
| Excretion in Urine of UX016 and SA | Baseline, 12 Weeks |
| Free, Total, and Calculated Bound Sialic Acid (SA) in Muscle (Quadriceps) Change From Baseline | Baseline, 12 Weeks |
| Lower Extremity Composite (LEC) Score Change From Baseline | Baseline, 48 Weeks |
| 6-Minute Walk Test (6MWT) Change From Baseline | Baseline, 48 Weeks |
| GNEM Functional Activities Scale (GNEM-FAS) Change From Baseline | Baseline, 48 Weeks |
Countries
United States
Contacts
CONTACTPatient Contact: Trial Recruitment
CONTACTHCP Contact: Medical Information
STUDY_DIRECTORMedical Director
Ultragenyx Pharmaceutical Inc
Outcome results
None listed