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

Primary Purpose

GM2 Gangliosidoses, Tay-Sachs, Sandhoff Disease

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Zavesca (Miglustat)
Sponsored by
Children's National Research Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for GM2 Gangliosidoses

Eligibility Criteria

6 Months - 5 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's National Medical Center

Outcomes

Primary Outcome Measures

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 Outcome Measures

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.

Full Information

First Posted
May 2, 2008
Last Updated
May 5, 2008
Sponsor
Children's National Research Institute
Collaborators
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT00672022
Brief Title
Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses
Official Title
Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset GM2 Gangliosidosis: Single and Steady State Oral Doses
Study Type
Interventional

2. Study Status

Record Verification Date
July 2005
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Children's National Research Institute
Collaborators
Actelion

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GM2 Gangliosidoses, Tay-Sachs, Sandhoff Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zavesca (Miglustat)
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Neurophysiologic Assessment - EEG and BEAR tests will be done at initial visit (run-in period), Week 13, and Week 25.
Title
Ophthalmology Assessment - comparision of the "cherry-red" macula changes will be made at initial visit (run-in period) and Week 25.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria 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. Exclusion criteria 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia J TIfft, MD, PhD
Organizational Affiliation
Children's National Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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