- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01303146
Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation (Azylis)
February 23, 2011 updated by: Assistance Publique - Hôpitaux de Paris
and Safety of METAZYM (Recombinant Human Arylsulfatase A or rhASA) for the Treatment of Patients With Late Infantile MLD Who Had Previously Hematopoietic Stem Cell Transplantation
There is currently no effective treatment for late infantile MLD once clinical symptoms are evident.
METAZYM is a recombinant human arylsulfatase A developed for an intravenous ERT for the treatment of late infantile MLD.
The overall objective of this study is to evaluate the efficacy and safety of intravenous rhASA treatment in a patient with late infantile MLD who had previously received hematopoietic stem cell transplantation (HCT).
Study Overview
Detailed Description
Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disorder caused by the deficiency of the Arylsulfatase A enzyme (ARSA), resulting in accumulation of galactosyl sulfatide (cerebroside sulfate), a major constituent of the myelin sheath.
Accumulation of galactosyl sulfatides leads to a progressive degeneration of the white matter in the central and peripheral nervous system (CNS, PNS) and neuronal degeneration.
The late infantile form of MLD, which usually is diagnosed in the second year of life, is the most frequent and severe form of the disease.
The prognosis is severe, leading to vegetative stage or death within few years after the diagnosis.
There is no treatment for patients affected with this early onset form of the disease.
In patients with late-onset MLD (juvenile and adult forms), allogeneic hematopoietic stem cell transplantation can stabilize the cerebral demyelination.
This treatment is however inefficient in patients with late infantile MLD at a symptomatic stage.
The overall objective is to evaluate the efficacy and safety of rhASA treatment in a patient with late infantile MLD who had received HCT at a presymptomatic stage of the disease.
Patient will receive rhARSA (100 U/kg) intravenously every other week for a period of 18 months.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Paris, France, 75014
- Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 months and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities.
- The patient must have a confirmed diagnosis of MLD as defined by:ARSA activity < 10 nmol/h/mg in leukocytes prior to HCT; Presence of elevated sulfatide in urine prior to HCT
- The patient must have a residual level of voluntary function (as judged by the investigator), including presence of residual cognitive function (attention, executive and visual functions) as well as the presence of residual voluntary motor function in one upper or lower limb as a minimum.
- The patient must have an age at the time of screening ≥ 6 months
- The patient must have had onset of symptoms before the age of 4 years
- The subject and his/her guardian(s) must have the ability to comply with the clinical protocol
- The patients' medical record must document that the legal guardian(s) has had independent counselling or a consultation regarding stem cell transplantation in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative
Exclusion Criteria:
Patient will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply:
- Presence of a gross motor function measure (GMFM < 25)
- Presence of severe pseudo-bulbar signs (weakness and disco-ordination of tongue and swallowing muscles leading to severe difficulty with swallowing)
- Spasticity so severe to inhibit transportation
- Known multiple sulfatase deficiency
- Presence of major congenital abnormality
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development
- Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
- Use of any investigational product within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations
- Received ERT with rhASA from any source
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Enzyme replacement therapy
intravenous infusion 100U/kg every other week for 18 months
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intravenous infusion 100U/kg every other week for 18 months
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;
Time Frame: every 6 months
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every 6 months
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Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;
Time Frame: week 26
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week 26
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Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months
Time Frame: every 6 months
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every 6 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy of METAZYM on central nervous system involvement by evaluation of cognitive and neurological function, somatosensory and auditory evoked potentials, and brain MRI every 6 months;
Time Frame: every 6 months
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every 6 months
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Safety profile of METAZYM by monitoring AE's, vital sign parameters and physical examination findings before each injection, as well as ECGs and routine clinical laboratory tests every 3 months.
Time Frame: every 3 months
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every 3 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Patrick Aubourg, MD, PhD, Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital, Paris
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2008
Primary Completion (Actual)
March 1, 2010
Study Completion (Actual)
April 1, 2010
Study Registration Dates
First Submitted
February 23, 2011
First Submitted That Met QC Criteria
February 23, 2011
First Posted (Estimate)
February 24, 2011
Study Record Updates
Last Update Posted (Estimate)
February 24, 2011
Last Update Submitted That Met QC Criteria
February 23, 2011
Last Verified
February 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Demyelinating Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Leukoencephalopathies
- Hereditary Central Nervous System Demyelinating Diseases
- Sulfatidosis
- Leukodystrophy, Metachromatic
Other Study ID Numbers
- P070805
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metachromatic Leukodystrophy
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Assistance Publique - Hôpitaux de ParisEuropean Leukodystrophy AssociationCompletedLate Infantile Metachromatic LeukodystrophyFrance
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ShireTerminatedMetabolic Diseases | Brain Diseases | Central Nervous System Diseases | Nervous System Diseases | Demyelinating Diseases | Genetic Diseases, Inborn | Metabolism, Inborn Errors | Lysosomal Storage Diseases | Lipid Metabolism Disorders | Sphingolipidoses | Hereditary Central Nervous System Demyelinating Diseases and other conditionsUnited States, Denmark, France, Argentina, Belgium, Brazil, Canada, Germany, Japan, Turkey