Open-Label Extension Study of Recombinant Human Arylsulfatase A (HGT-1111) in Late Infantile MLD

Study Overview
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Brief Summary
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This is a multi-center, open-label, extension study of patients with late infantile MLD who have previously completed clinical study HGT-MLD-048 (NCT00633139), defined as the completion of all Week 52 procedures. This group of patients will be offered ongoing treatment with HGT-1111 in this protocol. One infusion will be given every other week until the product is commercially available, the patient discontinues, or the study is terminated by the Sponsor, provided no safety issues have emerged.

Detailed Description
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The primary objective of this study is to provide ongoing treatment of HGT-1111 to patients who have completed study HGT-MLD-048 (previously study rhASA-03 - NCT00633139) until HGT-1111 is commercially available or the study is terminated by the Sponsor, provided no safety concerns have emerged. The secondary objective of this study is to monitor disease progression and the safety profile of HGT-1111 administered to patients who have completed study HGT-MLD-048 (NCT00633139).

Official Title
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A Multi-center, Open-Label Extension Study of HGT-1111 (Recombinant Human Arylsulfatase A or rhASA) Treatment in Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Conditions
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Late Infantile Metachromatic Leukodystrophy

Intervention / Treatment
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* Drug: HGT-1111


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Completion of study HGT-MLD-048 (NCT00633139) The subject and his/her guardian(s) must have the ability to comply with the 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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 6 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HGT-1111 100 U/kg<br> | Drug: HGT-1111<br>* Patients currently dosed with 100 U/kg or 200 U/kg will continue this treatment. Patients dosed with 50 U/kg will be equally randomized to treatment on 100 U/kg or 200 U/kg. The dose will be adjusted every 6-week to account for changes in body weight.The infusion length will be dependent on the dose. Infusion of 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.<br>* Other names: rhASA, Metazym;|
| Experimental: HGT-1111 200 U/kg<br> | Drug: HGT-1111<br>* Patients currently dosed with 100 U/kg or 200 U/kg will continue this treatment. Patients dosed with 50 U/kg will be equally randomized to treatment on 100 U/kg or 200 U/kg. The dose will be adjusted every 6-week to account for changes in body weight.The infusion length will be dependent on the dose. Infusion of 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.<br>* Other names: rhASA, Metazym;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of Exposure to HGT-1111 | End of study was defined as until HGT-1111 was commercially available, the participant's participation was discontinued, or the study was terminated by the Sponsor. | Baseline until end of study (Week 139) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Cerebrospinal Fluid (CSF) Sulfatide | Level of CSF sulfatide measured at 6-month intervals in HGT-MLD-049 (NCT00681811). | Baseline until end of study (Week 139) | 
| Level of White Matter Metabolites | Level of white matter metabolites [N-acetyl Aspartate (NAA)] measured at 6-month intervals in HGT-MLD-049 (NCT00681811). | Baseline until end of study (Week 139) | 
| Score of Gross Motor Function Measurement (GMFM) | Gross motor function was measured using GMFM-88 at 6-month intervals. The GMFM-88 item scores were summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score was between 0 (minimal) to 3 (maximum). The total GMFM-88 score was between 0 (minimal) to 264 (maximum). Decrease in GMFM score indicates disease progression. | Baseline until end of study (Week 139) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metazyme, Late Infantile Metachromatic Leukodystrophy