Gangliosidoses GM2
Conditions
Keywords
pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat
Brief summary
The purpose of the study is to investigate the pharmacokinetics of Zavesca (miglustat, OGT918) when given as single and multiple doses in juvenile patients with GM2 gangliosidosis.
Detailed description
The GM2 gangliosidoses are a group of neuro-degenerative lysosomal storage diseases resulting from accumulation of GM2 and related glycolipids in the central nervous system (CNS). Tay-Sachs and Sandhoff disease are two variants which are indistinguishable in clinical grounds. According to the onset and rate of disease progression, the condition can be categorized in infantile, juvenile and adult forms. This open-label, single-arm study is designed to assess the pharmacokinetics, safety and tolerability of miglustat in juvenile patients. Miglustat will be administered at a maximum dose of 600 mg/day, divided into three doses per day. The dose used for patients in this pediatric age range will be related to the patient's body surface area. The pharmacokinetics assessments for the study will be performed in-hospital during a 24 hour period, and will take place at the day one and at the month 3 visits. The clinical (which includes safety and tolerability) assessments will be performed throughout the 24-month study period.
Interventions
DRUGmiglustat
Target dose of 320 mg/m\^2/day (divided in 3 doses) will be based on the Body Surface Area (BSA). For children with a BSA \> 1.3, 200 mg TID will be administered. For children with a BSA of 0.8-1.3, 100 mg TID will be administered.
Sponsors
Actelion
The Hospital for Sick Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 20 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of GM2 gangliosidosis confirmed by demonstration of profound deficiency of β-hexosaminidase A or A & B in peripheral blood leukocytes or cultured skin fibroblasts * Aged 6 to 20 years * Onset of characteristic clinical symptoms of the disease before age 15 years * Normal renal or hepatic function
Exclusion criteria
* Fertile patients who do not agree to use adequate contraception throughout the study and for 3 months after cessation of miglustat treatment. * Patients who cannot tolerate the study procedures, cannot be compliant to therapy or who are unable to travel to the study center as required by this protocol. * Patients receiving other investigational agents within 3 months of study initiation. * Patients with disease that may affect absorption or elimination of drugs. * Patients suffering from clinically significant diarrhea (\>3 liquid stools per day for \> 7 days) without definable cause within 3 months of baseline visit, or who have a history of significant gastrointestinal disorders. * Patients with swallowing difficulties. * Patients with a high probability of dying during the study. * 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 |
|---|---|
| Concentration of miglustat in plasma | Periodic intervals up to 24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Changes in volume loss and signal intensity from baseline MRI | 12 months |
| Change in single-voxel N acetylaspartate (NAA) from baseline MRS | 1 month, 3 months, 6 months, 9 months, and 12 months |
| Change in neuropsychological testing from baseline | 6 months and 12 months |
| Change in nerve conduction | 6 months and 12 months |
| Change in neurological examination from baseline | 1 month, 3 months, 6 months, 9 months, and 12 months |
Countries
Canada
Outcome results
None listed