Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses

NCT00672022 | Completed Phase 3

• 1 other identifier: 3445
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

GM2 Gangliosidoses; Tay-Sachs; Sandhoff Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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.

Interventions

Zavesca (Miglustat) DRUG

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Onset of characteristic clinical symptoms of the disease before the age of 9 months.
• Normal renal and hepatic function.
• Written informed consent from parent or legal guardian.

You may not qualify if:

• 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.
• Patients receiving other investigational agents within 3 months of study initiation.
• Patients who are anemic (hemoglobin \< 11 g/dl, and/or hematocrit \< 34%)
• 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.
• Patients with a high probability of dying during the 6-month assessment period of the study.
• Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.

Sponsors & Collaborators

• Children's National Research Institute: lead
• Actelion: collaborator

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Gangliosidoses, GM2; Sandhoff Disease

Interventions

miglustat

Condition Hierarchy (Ancestors)

Gangliosidoses; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Cynthia J TIfft, MD, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 2, 2008
• First Posted: May 6, 2008
• Study Start: July 1, 2004
• Primary Completion: August 1, 2007
• Study Completion: August 1, 2007
• Last Updated: May 6, 2008

Record last verified: 2005-07

Locations

US (1)