Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Phase 1

Completed

Brief Summary: This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). All patients will be offered continuing treatment in this study and will in this protocol receive 13 infusions, whereby the patients total have had 27 infusions of Metazym. One infusion will be given every other week. After a total of 52 weeks of treatment the subjects will continue treatment in a compassionate use protocol. Safety (AE/SAE) will be monitored at every visit.

Recruitment & Eligibility

Inclusion Criteria

The patients from the Phase I trial must meet the following criteria to be enrolled in the study.

Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
The subject and his/her guardian(s) must have the ability to comply with the clinical protocol

Exclusion Criteria

Spasticity so severe to inhibit transportation
Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that, in the opinion of the Investigator, would preclude participation in the trial
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 other than rhASA within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations

Arm && Interventions

Group	Intervention	Description
Cohort 2	Recombinant human Arylsulfatase A (rhASA)	Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA)
Cohort 3	Recombinant human Arylsulfatase A (rhASA)	Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA)
Cohort 1	Recombinant human Arylsulfatase A (rhASA)	Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA)

Primary Outcome Measures

Name	Time	Method
Relative Changes (%) in Gross Motor Function Measurement (GMFM)	Baseline, 52 Weeks	Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean.
Relative Change in Mullen's Scales of Early Learning	Baseline, 52 Weeks	Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean.

Secondary Outcome Measures

Name	Time	Method
Change in Cerebrospinal Fluid (CSF) Sulfatide	Baseline, 52 Weeks	Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.