Metachromatic LeukodystrophyPhase 2AzylisNCT01303146
Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation
A Phase 2 study testing rhARSA in people with Metachromatic Leukodystrophy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Metachromatic Leukodystrophy
- What is being tested?
- rhARSA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2008to Apr 2010
- 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 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital
Paris, 75014
About this study
Official title: 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).
Read the 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.
- Conditions
- Metachromatic Leukodystrophy
- Being tested
- rhARSA
- Keywords
- Metachromatic Leukodystrophy, Enzyme replacement therapy, Allogeneic hematopoietic stem cell transplantation
- Medical subject headings
- Leukodystrophy, Metachromatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhARSADrug
Also called HGT-1111, Metazym
intravenous infusion 100U/kg every other week for 18 months
| Study group | Role | What they receive |
|---|---|---|
| Enzyme replacement therapy | Experimental | intravenous infusion 100U/kg every other week for 18 months Receives: Drug: rhARSA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;
Measured: every 6 months
Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;
Measured: week 26
Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months
Measured: every 6 months
Secondary outcomes (2)
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;
Measured: every 6 months
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.
Measured: every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study startOct 2008
- Primary completionMar 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metachromatic LeukodystrophyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- European Leukodystrophy Association, Zymenex A/S, Shire, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Patrick Aubourg, MD, PhD, Study chair, Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital, Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01303146
- Sponsor's protocol ID
- P070805
- Acronym
- Azylis
- Status last verified
- Mar 2026
- First submitted
- 23 Feb 2011
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01303146
- Acronym / sponsor ID
- Azylis / P070805
- Conditions
- Metachromatic Leukodystrophy
- Keywords
- Metachromatic Leukodystrophy, Enzyme replacement therapy, Allogeneic hematopoietic stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- European Leukodystrophy Association, Zymenex A/S, Shire, URC-CIC Paris Descartes Necker Cochin
- Study start
- Oct 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 24 Feb 2011 (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.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enzyme replacement therapy | Experimental | Drug: rhARSAintravenous infusion 100U/kg every other week for 18 months |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| rhARSAAlso: HGT-1111, Metazymintravenous infusion 100U/kg every other week for 18 months | Drug | Enzyme replacement therapy |
Primary outcome
Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;
Time frame: every 6 months
Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;
Time frame: week 26
Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months
Time frame: every 6 months
2 secondary outcomes
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
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
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 27 Mar 2026.
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Direct Lentiviral Injection Gene Therapy for MLD
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Lentiviral Hematopoietic Stem Cell Gene Therapy for MLD
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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.
Patrick Aubourg, MD, PhD study chair
Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital, Paris
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 rhARSA in people with Metachromatic Leukodystrophy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 inclusion and 11 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 27 Mar 2026. 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 France. 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?
Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months; (time frame: every 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Mar 2026.