Gangliosidoses GM2Phase 2NCT00418847
Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis
A Phase 2 study testing miglustat in people with Gangliosidoses GM2, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 20 years
- Conditions the study is for
- Gangliosidoses GM2
- What is being tested?
- miglustat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2004to Apr 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses
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.
Read the 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.
- Conditions
- Gangliosidoses GM2
- Being tested
- miglustat
- Keywords
- pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat
- Medical subject headings
- Gangliosidoses, GM2, Lysosomal Storage Diseases, Tay-Sachs Disease, Sandhoff Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
miglustatDrug
Also called Zavesca
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: miglustat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of miglustat in plasma
Measured: Periodic intervals up to 24 hours
Secondary outcomes (5)
Changes in volume loss and signal intensity from baseline MRI
Measured: 12 months
Change in single-voxel N acetylaspartate (NAA) from baseline MRS
Measured: 1 month, 3 months, 6 months, 9 months, and 12 months
Change in neuropsychological testing from baseline
Measured: 6 months and 12 months
Change in nerve conduction
Measured: 6 months and 12 months
Change in neurological examination from baseline
Measured: 1 month, 3 months, 6 months, 9 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2007 (estimated)
- Study startJul 2004
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gangliosidoses GM2Studies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Actelion
- Responsible party
- Sponsor
- Investigators
- Joe TR Clarke, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418847
- Sponsor's protocol ID
- 1000004763
- Status last verified
- May 2016
- First submitted
- 4 Jan 2007
- Last updated
- 19 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19595619
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses
- ClinicalTrials.gov ID
- NCT00418847
- Acronym / sponsor ID
- 1000004763
- Conditions
- Gangliosidoses GM2
- Keywords
- pediatrics, lysosomal storage diseases, Gangliosidoses GM2, Tay-Sachs disease, Sandhoff disease, Infantile GM2-activator deficiency, Miglustat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Actelion
- Study start
- Jul 2004
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 5 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: miglustat |
Who may qualify
- Ages
- 6 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| miglustatAlso: ZavescaTarget 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. | Drug | 1 |
Primary outcome
Concentration of miglustat in plasma
Time frame: Periodic intervals up to 24 hours
5 secondary outcomes
Changes in volume loss and signal intensity from baseline MRI
Time frame: 12 months
Change in single-voxel N acetylaspartate (NAA) from baseline MRS
Time frame: 1 month, 3 months, 6 months, 9 months, and 12 months
Change in neuropsychological testing from baseline
Time frame: 6 months and 12 months
Change in nerve conduction
Time frame: 6 months and 12 months
Change in neurological examination from baseline
Time frame: 1 month, 3 months, 6 months, 9 months, and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2016.
- Results publication: PubMed 19595619Maegawa 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.
Related trials for Gangliosidoses GM2
RecruitingObservational study
Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Neurological Regression, Myoclonus
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease (NPC)
Niemann-Pick Type C Disease
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease, GM1 Gangliosidosis or GM2 Gangliosidosis
Niemann-Pick Type C Disease, GM1 Gangliosidosis
Not yet recruitingPhase 2/3
Long-Term Safety and Tolerability of Nizubaglustat in Participants With Rare Lysosomal Disorders
Niemann-Pick Disease Type C, GM2 Gangliosidosis
Active, not recruitingPhase 2
A Study to Evaluate the Safety and Efficacy of Nizubaglustat (AZ-3102) in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease
GM2 Gangliosidosis, Niemann-Pick Type C Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joe TR Clarke, MD principal investigator
The Hospital for Sick Children, Toronto Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing miglustat in people with Gangliosidoses GM2, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of miglustat in plasma (time frame: Periodic intervals up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00418847, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2016.