Clinical Trial: Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Transpl

Brief 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. 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 Summary: 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.
Sponsor: Assistance Publique - Hôpitaux de Paris

Current 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 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: February 23, 2011
Date Started: October 2008
Date Completion:
Last Updated: February 23, 2011
Last Verified: February 2011