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

Primary Purpose

Gangliosidoses GM2

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

miglustat

About this trial

This is an interventional treatment trial for Gangliosidoses GM2 focused on measuring pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat

Eligibility Criteria

6 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

The Hospital for Sick Children

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Concentration of miglustat in plasma

Secondary Outcome Measures

Changes in volume loss and signal intensity from baseline MRI

Change in single-voxel N acetylaspartate (NAA) from baseline MRS

Change in neuropsychological testing from baseline

Change in nerve conduction

Change in neurological examination from baseline

Full Information

NCT ID

NCT00418847

First Posted

January 4, 2007

Last Updated

May 18, 2016

Sponsor

The Hospital for Sick Children

Collaborators

Actelion

1. Study Identification

Unique Protocol Identification Number

NCT00418847

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Completed

Study Start Date

July 2004 (undefined)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Hospital for Sick Children

Collaborators

Actelion

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gangliosidoses GM2

Keywords

pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

miglustat

Other Intervention Name(s)

Zavesca

Intervention Description

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.

Primary Outcome Measure Information:

Title

Concentration of miglustat in plasma

Time Frame

Periodic intervals up to 24 hours

Secondary Outcome Measure Information:

Title

Changes in volume loss and signal intensity from baseline MRI

Time Frame

12 months

Title

Change in single-voxel N acetylaspartate (NAA) from baseline MRS

Time Frame

1 month, 3 months, 6 months, 9 months, and 12 months

Title

Change in neuropsychological testing from baseline

Time Frame

6 months and 12 months

Title

Change in nerve conduction

Time Frame

6 months and 12 months

Title

Change in neurological examination from baseline

Time Frame

1 month, 3 months, 6 months, 9 months, and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joe TR Clarke, MD

Organizational Affiliation

The Hospital for Sick Children, Toronto Canada

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

19595619

Citation

Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT. Substrate reduction therapy in juvenile GM2 gangliosidosis. Mol Genet Metab. 2009 Sep-Oct;98(1-2):215-24. doi: 10.1016/j.ymgme.2009.06.005. Epub 2009 Jun 12.

Results Reference

result

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

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