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)

Conditions: Hereditary Inclusion Body Myopathy; Distal Myopathy With Rimmed Vacuoles; Distal Myopathy, Nonaka Type; GNE Myopathy

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.


Eligibility criteria:
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

Keywords: gne myopathy gnem hibm nonaka hereditary inclusion body myopathy dmrv