Primary Outcome Measures:
- To evaluate the safety profile of Metazym [ Time Frame: One year ] [ Designated as safety issue: Yes ]
- To determine the PK profile of Metazym in patients with late infantile MLD as measured by rhASA levels in plasma and ASA activity in leukocytes [ Time Frame: One year ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Efficacy of Metazym on the biochemical level, by assessing sulfatide concentrations in urine and cerebrospinal fluid, and changes in cerebrospinal fluid biomarkers [ Time Frame: One year ] [ Designated as safety issue: No ]
- Efficacy of Metazym on functional capacity (disability level), by assessing gross and fine motor function, adaptive and cognitive development [ Time Frame: One year ] [ Designated as safety issue: No ]
Intervention Details:
Drug: Metazym
The lowest dose level will be evaluated as a single dose of 25 U/kg. The three upper dose levels will be evaluated as repeated doses. Patients in each cohort will receive one dose of enzyme every other week for a period of twenty-six weeks, a total of thirteen doses. Dosing will be performed as follows: Cohort 1: 25 U/kg as a single dose - hereafter 50 U/kg; Cohort 2: 100 U/kg; Cohort 3: 200 U/kg. Patients receiving the lowest dose as a single dose will receive the next dose level as a repeated dose.
Test product, dose, mode of administration, batch No.: The lowest dose level will be evaluated as a single dose of 25 U/kg. The three upper dose levels will be evaluated as repeated doses. Patients in each cohort will receive one dose of enzyme every other week for a period of eight weeks, a total of five doses. Dosing will be performed as follows: Cohort 1: 25 U/kg as a single dose - hereafter 50 U/kg; Cohort 2: 100 U/kg; Cohort 3: 200 U/kg. Patients receiving the lowest dose as a single dose will receive the next dose level as a repeated dose. After twenty six weeks the subjects will continue treatment every other week until safety data is available. Safety (AE/SAE) will be monitored at every visit during this period. The dose will be adjusted monthly to account for changes in body weight. The infusion length will be dependent on the dose. Doses of 25 U/kg, 50 U/kg and 100 U/kg will be diluted in 50 ml isotonic sodium chloride and infused over 30 minutes. Infusion of 200 U/kg will be administered in the same manner except for an infusion time of 60 minutes.
Duration of treatment: Half a year (26 weeks)