safety and pharmacokinetics of sialic acid tables in patients with hereditary inclusion body myopathy (hibm)

Conditions: Hereditary Inclusion Body Myopathy (HIBM)

Summary: hereditary inclusion body myopathy (hibm) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (sa), a critical component of many muscle proteins, resulting in a deficiency in sa in the muscles of hibm patients. the effective replacement of the missing sa substrate is theoretically simple, and, in animal models, replacement with sa showed significant restoration of sialylation biochemistry and excellent reduction in muscle disease. these data show that replacement can achieve significant clinical benefit in muscle pathology, function, and survival.


Eligibility criteria:
inclusion criteria: 1. must be 18 years to 70 years of age. 2. willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. 3. must have a documented diagnosis, confirmed by genetic testing, of hereditary inclusion body myopathy (hibm), also known as distal myopathy, rimmed vacuoles (dmrv), or nonaka myopathy due to demonstrated mutations in gene encoding the gne/mnk enzyme. 4. willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or phase 1 unit. 5. sexually active subjects must be willing to use an acceptable method of contraception (i.e double barrier method)while participating in the study and for 30 days after receiving the last dose of sa-er. 6. 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 at least 2 years, or had bilateral tubal ligation at least 1 year prior to screening, or who have had total hysterectomy. exclusion criteria: 1. pregnant or breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study. 2. 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. 3. ingestion of mannac, sialic acid, or related metabolites or sialic acid donors that provide this substrate in either chemical or nutritional supplement form during the 30 days prior to screening. if mannac or other substrate was used more than 30 days prior to screening, the time period of use, the compound used, and the dose and dose regimen should be recorded in the patient's history. if a patient has been on substrate replacement therapy in the past, the investigator must consider the potential confounding effects of this therapy before enrolling the patient. 4. presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment. 5. presence or history of any hypersensitivity to sa or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects. 6. presence of a concurrent disease or condition that would interfere with study participation or affect safety such as swallowing difficulties. 7. presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study. 8. serum transaminase (alt, ast, ggt) levels \> 3 x upper limit of normal (uln) or serum creatinine \> 2.0 mg/dl.

Keywords: phase 1 safety and pharmacokinetic study