Clinical Trial: Intracerebral Gene Therapy for Children With Early Onset Forms of Metachromatic Leukodystrophy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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). 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.


Detailed Summary:
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Current 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).


Original Primary Outcome: Same as current

Current 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 ]

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).


Original Secondary Outcome: Same as current

Information By: Institut National de la Santé Et de la Recherche Médicale, France

Dates:
Date Received: January 28, 2013
Date Started: March 2013
Date Completion: April 2018
Last Updated: January 28, 2014
Last Verified: January 2014