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

Study Overview
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Brief Summary
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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.

Official Title
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A Single Center, Open-Label, Non-Randomized, Uncontrolled, Multiple-Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Efficacy and Long Term Safety of HGT-1111 (Recombinant Human Arylsulfatase A [rhASA, Metazym]) for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Conditions
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Late Infantile Metachromatic Leukodystrophy

Intervention / Treatment
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* Biological: Recombinant human Arylsulfatase A (rhASA)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA) | Biological: Recombinant human Arylsulfatase A (rhASA)<br>* intravenous infusion, every other week for 26 weeks<br>* Other names: HGT-1111;|
| Experimental: Cohort 2<br>Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA) | Biological: Recombinant human Arylsulfatase A (rhASA)<br>* intravenous infusion, every other week for 26 weeks<br>* Other names: HGT-1111;|
| Experimental: Cohort 3<br>Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA) | Biological: Recombinant human Arylsulfatase A (rhASA)<br>* intravenous infusion, every other week for 26 weeks<br>* Other names: HGT-1111;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Changes (%) in Gross Motor Function Measurement (GMFM) | 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. | Baseline, 52 Weeks | 
| Relative Change in Mullen's Scales of Early Learning | 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. | Baseline, 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cerebrospinal Fluid (CSF) Sulfatide | Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean. | Baseline, 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metazym, Late infantile, Metachromatic leukodystrophy, Long-term safety