Late infantile metachromatic leukodystrophy (MLD) MedDRA version: 9.1 Level: LLT Classification code 10024381 Term: Leukodystrophy
Conditions
Interventions
Product Name: Metazym
Product Code: rhASA
Pharmaceutical Form: Injection*
INN or Proposed INN: Arylsulfatase A
Current Sponsor code: rhASA
Other descriptive name: Metazym
Concentration unit: IU/ml int
Sponsors
Shire Pharmaceuticals Ireland Limited
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of a gross motor function measure (GMFM < 10) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety profile of Metazym 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 ;Secondary Objective: Efficacy of Metazym on the biochemical level, by assessing sulfatide concentrations in urine and cerebrospinal fluid, and changes in cerebrospinal fluid biomarkers Efficacy of Metazym on functional capacity (disability level), by assessing gross and fine motor function, adaptive and cognitive development ;Primary end point(s): From the safety evaluation a maximum tolerated dose (MTD) is determined by a DMC (on the basis of evaluation after each dose group) and this is the primary safety endpoint. All adverse events will be summarized overall by use of system organ class and preferred terms in MEDDRA code summarized by dose level. Adverse events will be accounted for in relation to the dose level used at the time for onset of the event. Serious adverse events will be summarized separately in similar form. All adverse events will in addition be summarized according to dose level, severity and according to relationship to study drug as assessed by investigator. Changes from normal to abnormal will be presented in shift tables for all laboratory variables for whom reference ranges are available. Urine-analysis, ECG and physical examination will be presented descriptively by dose level, only. The following PK endpoints are derived and will be analyzed: rhASA in blood and ASA activity in leukocytes will be presented graphically. AUC, Cmax, Tmax, T½ (if applicable) will be derived by trapzodial method and presented descriptively by dose level. Functional capacity GMFM is the primary efficacy endpoint. Item scores can be summed to calculate raw and percent score for each of the five GMFM dimensions. Biochemical markers Urinary sulfatide, CSF sulfatide, chitotriosidase, NFp, GFAp, tau protein are all measured on a continuous scale. Nerve conduction | — |
Countries
Denmark
Outcome results
None listed