GM2 Gangliosidoses, Sandhoff Disease, Tay-Sachs
Conditions
Brief summary
We want to see if Zavesca (or miglustat) is safe and can be tolerated by patients with acute infantile onset GM2 gangliosidosis - classical Tay-Sachs and infantile onset Sandhoff disease. We know that miglustat inhibits the formation of GM2 ganglioside, the compound that is stored in the brains of children with Tay-Sachs and Sandhoff disease. Since it inhibits the synthesis of ganglioside, miglustat may be able to reduce or delay the onset of clinical symptoms.
Detailed description
Specific Aims The primary objective of the study is to investigate the pharmacokinetics of ZAVESCA® (miglustat, OGT918), when given as a single dose and at steady state, in infantile patients with GM2 gangliosidosis. The secondary objectives are to evaluate the tolerability and safety of single and multiple doses of miglustat and to monitor disease progression using physical and developmental assessments and disease-specific biomarkers.
Interventions
DRUGZavesca (Miglustat)
Sponsors
Actelion
Children's National Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of GM2 gangliosidosis, confirmed by demonstration of profound deficiency of -hexosaminidase A or A & B in peripheral blood leukocytes or in cultured skin fibroblasts, within the previous 1 year in non-bone marrow transplant recipients who are \< 2 years of age, or prior to stem cell transplant in stably engrafted transplant patients who are \< 5 years of age. 2. Onset of characteristic clinical symptoms of the disease before the age of 9 months. 3. Normal renal and hepatic function. 4. Written informed consent from parent or legal guardian.
Exclusion criteria
1. Patients who are unable to comply with the study procedures of this protocol, including the refusal to swallow the food used to mask the taste of the study drug and whose parents are unwilling to administer the drug through a nasogastric or gastrostomy tube. 2. Patients receiving other investigational agents within 3 months of study initiation. 3. Patients who are anemic (hemoglobin \< 11 g/dl, and/or hematocrit \< 34%) 4. Patients who have a history of significant gastrointestinal disorders, including clinically significant diarrhea (\>3 liquid stools per day for \> 7 days), without definable cause within 3 months of baseline visit. 5. Patients with a high probability of dying during the 6-month assessment period of the study. 6. Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Biomarkers (level of GM2 ganglioside, chitotriosidase activity, anti-GM2 antibodies) in plasma, serum and CSF will be measured at initial visit (run-in period), Week 13, and Week 25. | — |
Secondary
| Measure | Time frame |
|---|---|
| Neurophysiologic Assessment - EEG and BEAR tests will be done at initial visit (run-in period), Week 13, and Week 25. | — |
| Ophthalmology Assessment - comparision of the cherry-red macula changes will be made at initial visit (run-in period) and Week 25. | — |
Countries
United States
Outcome results
None listed