Early onset forms of MLD MedDRA version: 14.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders MedDRA version: 14.1 Level: PT Classification code 10067609 Term: Metachromatic leukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: SOC Classification code 10027433 Term: Metabolism and nutrition disorders System Organ Class: 10027433 - Metabolism and nutriti
Conditions
Interventions
Product Name: AAVrh.10cuARSA
Product Code: Non applicable
Pharmaceutical Form: Solution for injection
Sponsors
Inserm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Boys or girls with an ealry onset form of MLD - Age between 6 months ans 4 years, inclusive - Interval between age of first symptoms and age of inclusion muyst be 12 or less months - 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. Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Absence of ARSA protein by immunocytochemistry and/or ELISA - Gestational age 10mm in the frontal region. -MLD MRI severity score >14 - Performance IQ16 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 - Malignancy cardiac malformation, liver dysfunction, or renal dysfuncion - 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 impossibilty - Evoked potential impossibility - Participation to another therapeutic clinical trial for MLD - Unaffiliated to any French health insurance or any other European National Health Insurance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary goal of the trial is the assessment of tolerance (safety) of the intracerebral adminsitration of a single dose of AAVrh.10cuARSA ;Secondary Objective: Evaluate the efficacy of intracerebral administration of a single dose of a AAVrh.210cuARSA to stop the disease progression;Primary end point(s): A) SAFETY Early follow-up: safety or neurosurgical procedure (M0-M1) - Standard clinical and neurological exam and monitoring of adverse events associated to the procedure - Standard laboratory tests - CT scan - Brain MRI Follow-up after the neurosurgical procedure (M1-M24) - Standard clinical and laboratory tests and adverse event monitoring - Brain MRI B) Primary efficacy endpoint MLD neurological severity score;Timepoint(s) of evaluation of this end point: A) SAFETY Early follow-up: safety or neurosurgical procedure (M0-M1) - Standard clinical and neurological exam and monitoring of adverse events associated to the procedure: day +1, +3, +7, +10 and months +1 - Standard laboratory tests: day +3, +10, and months +1 - CT scan: within 36 hours of the procedure - Brain MRI day +6 and month +1 Follow-up after the neurosurgical procedure (M1-M24) - Standard clinical and laboratory tests and adverse event monitoring months 1,3,6,9,15 18 and 24 - Brain MRI months +3, +9, +15 and +24 B) Primary efficacy endpoint MLD neurological severity score at months +1, +3, +6, +12 +18 and +24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Motor scores (GMFM, Ashworth and ICARS) Neurological evaluation Cognitive functions (Bayey Scales of Infant Development MLD severity MRI score, MRI-DTI parameters, measurement of cerebral atrophy and spectroscopy Neuroelectrophysiological tests (peripheral nerve condution velocity, visual, auditory and somatosensory evoked potentials);Timepoint(s) of evaluation of this end point: Motor scores (GMFM, Ashworth and ICARS): at months +1, +3 for GMFM ans Ahshworth tests only, and +6, +12, +18and +24 for all tests Neurological evaluation at each visit. Cognitive functions (Bayey Scales of Infant Development at months +3, +9, +15 and +24. MLD severity MRI score, MRI-DTI parameters, measurement of cerebral atrophy and spectroscopy at months +1, +3, +6, +9, +15 and +24. Neuroelectrophysiological tests (peripheral nerve condution velocity, visual, auditory at months +3, 15 and +24 and somatosensory evoked potentials) | — |
Countries
France
Contacts
Public ContactAnne PUECH
Inserm
Outcome results
None listed