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

Primary Purpose

Metachromatic Leukodystrophy

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
rhARSA
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metachromatic Leukodystrophy focused on measuring Metachromatic Leukodystrophy, Enzyme replacement therapy, Allogeneic hematopoietic stem cell transplantation

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

Patient will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply:

  • 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Enzyme replacement therapy

Arm Description

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

Outcomes

Primary Outcome Measures

Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;
Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;
Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months

Secondary Outcome Measures

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;
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.

Full Information

First Posted
February 23, 2011
Last Updated
February 23, 2011
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
European Leukodystrophy Association, Zymenex A/S, Shire
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1. Study Identification

Unique Protocol Identification Number
NCT01303146
Brief Title
Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation
Acronym
Azylis
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 Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
European Leukodystrophy Association, Zymenex A/S, Shire

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metachromatic Leukodystrophy
Keywords
Metachromatic Leukodystrophy, Enzyme replacement therapy, Allogeneic hematopoietic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Enzyme replacement therapy
Arm Type
Experimental
Arm Description
intravenous infusion 100U/kg every other week for 18 months
Intervention Type
Drug
Intervention Name(s)
rhARSA
Other Intervention Name(s)
HGT-1111, Metazym
Intervention Description
intravenous infusion 100U/kg every other week for 18 months
Primary Outcome Measure Information:
Title
Efficacy of METAZYM on peripheral nerve function by electrophysiological studies (motor and sensory nerves conduction velocities) every 6 months;
Time Frame
every 6 months
Title
Efficacy of METAZYM on peripheral nerve sulfatide storage and demyelination by nerve biopsy at baseline and week 26;
Time Frame
week 26
Title
Efficacy of METAZYM on functional capacity by assessing motor function (GMFM) every 6 months
Time Frame
every 6 months
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: Patient will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Aubourg, MD, PhD
Organizational Affiliation
Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital, Paris
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Pediatric Endocrinology and Neurology, Saint Vincent de Paul Hospital
City
Paris
ZIP/Postal Code
75014
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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