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

NCT01303146 | Completed Phase 2

• 1 other identifier: P070805
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Metachromatic Leukodystrophy

Keywords

Metachromatic Leukodystrophy; Enzyme replacement therapy; Allogeneic hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (3)

• Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;

  every 6 months

• Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;

  week 26

• Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months

  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;

  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.

  every 3 months

Study Arms (1)

Enzyme replacement therapy

EXPERIMENTAL

intravenous infusion 100U/kg every other week for 18 months

Drug: rhARSA

Interventions

rhARSA DRUG

intravenous infusion 100U/kg every other week for 18 months

Also known as: HGT-1111, Metazym

Enzyme replacement therapy

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• European Leukodystrophy Association: collaborator
• Zymenex A/S: collaborator
• Shire: collaborator
• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital

Paris, 75014, France

Location

MeSH Terms

Conditions

Leukodystrophy, Metachromatic

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Patrick Aubourg, MD, PhD

  Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital, Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2011
• First Posted: February 24, 2011
• Study Start: October 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2010
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

FR (1)