Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses

Conditions
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Gangliosidoses GM2

Intervention / Treatment
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* Drug: miglustat


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: miglustat<br>* 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.<br>* Other names: Zavesca;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of miglustat in plasma |  | Periodic intervals up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat