Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
Condition: Metachromatic Leukodystrophy (MLD)
MeSH terms: Leukodystrophy, Metachromatic
Intervention: rhASA - Dose Level 1; rhASA - Dose Level 2; rhASA - Dose Level 3
Intervention description: Intravenous infusion 25 U/kg as a single dose - hereafter 50 U/kg every other week for 26 weeks; Intravenous infusion 100 U/kg every other week for 26 weeks; Intravenous infusion 200 U/kg every other week for 26 weeks
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 1 Year
Maximum age: 5 Years
Healthy volunteers: No
Keywords: rhASA; MLD; Metazym

Summary:

      Objectives: The overall objective is to evaluate the safety, efficacy and pharmacokinetics
      (PK) of rhASA treatment in patients with late infantile MLD.

      Methodology: This is a single center, open-label study of patients with late infantile MLD.
      Twelve patients will be enrolled in this study receiving a total of thirteen intravenous
      infusions of Metazym. One infusion will be given every other week for a period of half a
      year. After the half year 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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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).

          2. The patient must have a confirmed diagnosis of MLD as defined by:

             ASA activity < 10 nmol/h/mg in leukocytes Presence of elevated sulfatide in urine

          3. The patient must have a confirmed nerve conduction velocity < 2 standard deviations
             (from the appropriate age level)

          4. 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.

          5. The patient must have an age at the time of screening ≥ 1 year and < 6 years

          6. The patient must have had onset of symptoms before the age of 4 years

          7. The subject and his/her guardian(s) must have the ability to comply with the clinical
             protocol

          8. 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:

        Patients will be excluded from this study if they do not meet the specific inclusion
        criteria, or if any of the following criteria apply:

          1. Lack of voluntary function

          2. Presence of severe pseudo-bulbar signs (weakness and disco-ordination of tongue and
             swallowing muscles leading to severe difficulty with swallowing)

          3. Spasticity so severe to inhibit transportation

          4. Known multiple sulfatase deficiency

          5. Presence of major congenital abnormality

          6. Presence of known chromosomal abnormality and syndromes affecting psychomotor
             development

          7. History of stem cell transplantation

          8. Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal
             disease or other medical condition

          9. Any other medical condition or serious intercurrent illness, or extenuating
             circumstance that, in the opinion of the Investigator, would preclude participation in
             the trial

         10. Use of any investigational product within 30 days prior to study enrolment or
             currently enrolled in another study which involves clinical investigations

         11. Received ERT with rhASA from any source

         12. Planned or anticipated initiation of antispastic treatment after trial initiation