Metachromatic LeukodystrophyPhase 1/2TG-MLDNCT01801709
Intracerebral Gene Therapy for Children With Early Onset Forms of Metachromatic Leukodystrophy
A Phase 1/2 study testing intracerebral administration of AAVrh.10cuARSA in people with Metachromatic Leukodystrophy, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
The objective of this open-label, single arm, monocentric, phase I/II clinical study is to assess safety and efficacy of ARSA gene transfer in the brain of children affected with early onset forms of Metachromatic Leukodystrophy (MLD). Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Metachromatic Leukodystrophy
- What is being tested?
- intracerebral administration of AAVrh.10cuARSA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2014to 20 Dec 2022
- Phase
- Phase 1/2
- 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 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Boys or girls with an early onset form of MLD.
- Age between 6 months and 5 years, inclusive
- Diagnostic of MLD based on the measurement of ARSA activity in leukocytes and the accumulation of sulfatides in urine, along with normal activity of at least one other sulfatase
- Informed consent signed up and willingness for monitoring 2 years after treatment.
- Normal values for standard laboratory tests
Who cannot join
- Absence of ARSA protein by immunocytochemistry and/or ELISA
- Gestational age <32 weeks of amenorrhoea and age < 1 year
- Brain atrophy with a subdural space > 10 mm in the frontal region
- Performance IQ<50 at WPPSI-III or cognitive function < 3rd percentile at the Bayley's test of infant development
- If age > 16 months at inclusion, inability to walk few steps alone OR inability to walk few steps with support on one side along with inability to stand up alone
- Impossibility for anesthesia
Show all 13Show fewer
- Malignancy, cardiac malformation, liver dysfunction, or renal dysfunction
- Neurological disorder, except benign, not related to MLD.
- Any other clinically significant untreated co-morbid medical condition as determined by the clinical investigator, including cardiac, pulmonary or kidney disease.
- MRI impossibility
- Evoked potential impossibility
- Participation to another therapeutic clinical trial for MLD.
- Unaffiliated to any French or any other National Health Insurance.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II, Open Labeled, Monocentric Study of Direct Intracranial Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human ARSA cDNA to Children With Metachromatic Leukodystrophy.
The objective of this open-label, single arm, monocentric, phase I/II clinical study is to assess safety and efficacy of ARSA gene transfer in the brain of children affected with early onset forms of Metachromatic Leukodystrophy (MLD). For this purpose, an adeno-associated virus serotype rh.10 (AAVrh.10) vector will be used to transfer the ARSA cDNA coding for Arylsulfatase A (ARSA) enzyme into the brain of children. Five patients with early onset form of MLD, age ranging from 6 months to 4 years, will be included in this protocol and will be followed during 24 months.
Patients will be selected at presymptomatic or early stage of their disease, following clinical, neuropsychological and brain imaging criteria.
Read more
Twelve simultaneous injections of the investigational medicinal product will be performed in the white matter of both brain hemispheres, through 6 image-guided tracks, with 2 deposits per track.
A low dose (1x10EXP12 vg total) will be administered to the first 2 patients, while the last 3 will receive a higher dose (4x10EXP12 vg total).
Safety and efficiency will be evaluated based on clinical, neuropsychological, radiological, electrophysiological and biological parameters.
- Conditions
- Metachromatic Leukodystrophy
- Being tested
- intracerebral administration of AAVrh.10cuARSA
- Keywords
- Brain Gene Therapy, Adeno Associated vector, Lysosomal sotage diseases, Leukodystrophies
- Medical subject headings
- Leukodystrophy, Metachromatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intracerebral administration of AAVrh.10cuARSAGenetic
| Study group | Role | What they receive |
|---|---|---|
| AAVrh.10cuARSA | Experimental | intracerebral administration of AAVrh.10cuARSA at 12 sites in the white matter of both brain hemispheres. Receives: Genetic: intracerebral administration of AAVrh.10cuARSA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the tolerance of the intracerebral administration of a single dose of AAVrh.10cuARSA
Tolerance will be measured by :
- Adverse event,
- Clinical and neurological exams,
- Laboratory tests,
- Neuroimagery (CT scan, brain MRI).
Measured: During the two years follow-up
Secondary outcomes (1)
Evaluate the efficacy of intracerebral administration of a single dose of AAVrh.10cuARSA to stop the disease progression.
Efficacy will be measured by:
- MLD neurological severity score,
- Neurological evaluation,
- Motor scores (GMFM, Ashworth and ICARS),
- Cognitive functions (Bayley Scales of Infant Development (BSID)(0-42 months), or Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III) (43 months-6 years)),
- MLD severity MRI score, MRI-DTI parameters, measurement of cerebral atrophy and spectroscopy,
- Neuroelectrophysiological tests (peripheral nerve conduction velocity, visual, auditory and somatosensory evoked potentials).
Measured: During the two years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2013 (estimated)
- Study startJun 2014
- Primary completionJun 2016
- Study completion20 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metachromatic LeukodystrophyStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- European Leukodystrophy Association, Assistance Publique - Hôpitaux de Paris
- Responsible party
- Sponsor
- Investigators
- Patrick Aubourg, MD-PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris and Institut National de la Santé et de la Recherche MédicaleCaroline Sevin, MD-PhD, Study director, Assistance Publique - Hôpitaux de ParisMichel Zerah, MD, PhD, Study director, Assistance Publique - Hôpitaux de ParisThomas Roujeau, MD, PhD, Study director, Assistance Publique - Hôpitaux de ParisNathalie Cartier, MD, PhD, Study director, Institut National de la Santé et de la Recherche Biomédicale
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01801709
- Sponsor's protocol ID
- C11-09
- Other IDs
- 2011-004410-42
- Acronym
- TG-MLD
- Status last verified
- Jan 2025
- First submitted
- 28 Jan 2013
- Last updated
- 2 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Piguet F, Sondhi D, Piraud M, Fouquet F, Hackett NR, Ahouansou O, Vanier MT, Bieche I, Aubourg P, Crystal RG, Cartier N, Sevin C. Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice. Hum Gene Ther. 2012 Aug;23(8):903-14. doi: 10.1089/hum.2012.015. Epub 2012 Jul 23.
PubMed 22642214Sondhi D, Johnson L, Purpura K, Monette S, Souweidane MM, Kaplitt MG, Kosofsky B, Yohay K, Ballon D, Dyke J, Kaminksy SM, Hackett NR, Crystal RG. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther Methods. 2012 Oct;23(5):324-35. doi: 10.1089/hgtb.2012.120. Epub 2012 Nov 6.
PubMed 23131032Colle MA, Piguet F, Bertrand L, Raoul S, Bieche I, Dubreil L, Sloothaak D, Bouquet C, Moullier P, Aubourg P, Cherel Y, Cartier N, Sevin C. Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate. Hum Mol Genet. 2010 Jan 1;19(1):147-58. doi: 10.1093/hmg/ddp475.
PubMed 19837699i Dali C, Hanson LG, Barton NW, Fogh J, Nair N, Lund AM. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy. Neurology. 2010 Nov 23;75(21):1896-903. doi: 10.1212/WNL.0b013e3181feb217.
PubMed 21098404Zerah M, Piguet F, Colle MA, Raoul S, Deschamps JY, Deniaud J, Gautier B, Toulgoat F, Bieche I, Laurendeau I, Sondhi D, Souweidane MM, Cartier-Lacave N, Moullier P, Crystal RG, Roujeau T, Sevin C, Aubourg P. Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical Feasibility and Safety Assessments in Nonhuman Primates. Hum Gene Ther Clin Dev. 2015 Jun;26(2):113-24. doi: 10.1089/humc.2014.139. Epub 2015 Apr 28.
PubMed 25758611
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Labeled, Monocentric Study of Direct Intracranial Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human ARSA cDNA to Children With Metachromatic Leukodystrophy.
- ClinicalTrials.gov ID
- NCT01801709
- Acronym / sponsor ID
- TG-MLD / C11-09
- Conditions
- Metachromatic Leukodystrophy
- Keywords
- Brain Gene Therapy, Adeno Associated vector, Lysosomal sotage diseases, Leukodystrophies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- European Leukodystrophy Association, Assistance Publique - Hôpitaux de Paris
- Study start
- Jun 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 1 Mar 2013 (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 objective of this open-label, single arm, monocentric, phase I/II clinical study is to assess safety and efficacy of ARSA gene transfer in the brain of children affected with early onset forms of Metachromatic Leukodystrophy (MLD). For this purpose, an adeno-associated virus serotype rh.10 (AAVrh.10) vector will be used to transfer the ARSA cDNA coding for Arylsulfatase A (ARSA) enzyme into the brain of children. Five patients with early onset form of MLD, age ranging from 6 months to 4 years, will be included in this protocol and will be followed during 24 months.
Patients will be selected at presymptomatic or early stage of their disease, following clinical, neuropsychological and brain imaging criteria.
Twelve simultaneous injections of the investigational medicinal product will be performed in the white matter of both brain hemispheres, through 6 image-guided tracks, with 2 deposits per track.
A low dose (1x10EXP12 vg total) will be administered to the first 2 patients, while the last 3 will receive a higher dose (4x10EXP12 vg total).
Safety and efficiency will be evaluated based on clinical, neuropsychological, radiological, electrophysiological and biological parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AAVrh.10cuARSA | Experimental | Genetic: intracerebral administration of AAVrh.10cuARSAintracerebral administration of AAVrh.10cuARSA at 12 sites in the white matter of both brain hemispheres. |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Boys or girls with an early onset form of MLD.
- Age between 6 months and 5 years, inclusive
- Diagnostic of MLD based on the measurement of ARSA activity in leukocytes and the accumulation of sulfatides in urine, along with normal activity of at least one other sulfatase
- Informed consent signed up and willingness for monitoring 2 years after treatment.
- Normal values for standard laboratory tests
Key exclusion criteria (13 listed)
- Absence of ARSA protein by immunocytochemistry and/or ELISA
- Gestational age <32 weeks of amenorrhoea and age < 1 year
- Brain atrophy with a subdural space > 10 mm in the frontal region
- Performance IQ<50 at WPPSI-III or cognitive function < 3rd percentile at the Bayley's test of infant development
- If age > 16 months at inclusion, inability to walk few steps alone OR inability to walk few steps with support on one side along with inability to stand up alone
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 |
|---|---|---|
| intracerebral administration of AAVrh.10cuARSA | Genetic | AAVrh.10cuARSA |
Primary outcome
Evaluate the tolerance of the intracerebral administration of a single dose of AAVrh.10cuARSA
Time frame: During the two years follow-up
Tolerance will be measured by : * Adverse event, * Clinical and neurological exams, * Laboratory tests, * Neuroimagery (CT scan, brain MRI).
1 secondary outcome
Evaluate the efficacy of intracerebral administration of a single dose of AAVrh.10cuARSA to stop the disease progression.
Time frame: During the two years follow-up
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 2 Mar 2026.
- Background: PubMed 22642214Piguet F, Sondhi D, Piraud M, Fouquet F, Hackett NR, Ahouansou O, Vanier MT, Bieche I, Aubourg P, Crystal RG, Cartier N, Sevin C. Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice. Hum Gene Ther. 2012 Aug;23(8):903-14. doi: 10.1089/hum.2012.015. Epub 2012 Jul 23.
- Background: PubMed 23131032Sondhi D, Johnson L, Purpura K, Monette S, Souweidane MM, Kaplitt MG, Kosofsky B, Yohay K, Ballon D, Dyke J, Kaminksy SM, Hackett NR, Crystal RG. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther Methods. 2012 Oct;23(5):324-35. doi: 10.1089/hgtb.2012.120. Epub 2012 Nov 6.
- Background: PubMed 19837699Colle MA, Piguet F, Bertrand L, Raoul S, Bieche I, Dubreil L, Sloothaak D, Bouquet C, Moullier P, Aubourg P, Cherel Y, Cartier N, Sevin C. Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate. Hum Mol Genet. 2010 Jan 1;19(1):147-58. doi: 10.1093/hmg/ddp475.
- Background: PubMed 21098404i Dali C, Hanson LG, Barton NW, Fogh J, Nair N, Lund AM. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy. Neurology. 2010 Nov 23;75(21):1896-903. doi: 10.1212/WNL.0b013e3181feb217.
- Results publication: PubMed 25758611Zerah M, Piguet F, Colle MA, Raoul S, Deschamps JY, Deniaud J, Gautier B, Toulgoat F, Bieche I, Laurendeau I, Sondhi D, Souweidane MM, Cartier-Lacave N, Moullier P, Crystal RG, Roujeau T, Sevin C, Aubourg P. Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical Feasibility and Safety Assessments in Nonhuman Primates. Hum Gene Ther Clin Dev. 2015 Jun;26(2):113-24. doi: 10.1089/humc.2014.139. Epub 2015 Apr 28.
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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 principal investigator
Assistance Publique - Hôpitaux de Paris and Institut National de la Santé et de la Recherche Médicale
Caroline Sevin, MD-PhD study director
Assistance Publique - Hôpitaux de Paris
Michel Zerah, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing intracerebral administration of AAVrh.10cuARSA in people with Metachromatic Leukodystrophy, run by Institut National de la Santé Et de la Recherche Médicale, France 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 5 inclusion and 13 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 2 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Evaluate the tolerance of the intracerebral administration of a single dose of AAVrh.10cuARSA (time frame: During the two years follow-up). 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 NCT01801709, which also lists 5 linked publications.
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 2 Mar 2026.