Brain Diseases, Central Nervous System Diseases, Demyelinating Diseases, Genetic Diseases, Inborn, Hereditary Central Nervous System Demyelinating Diseases, Lipid Metabolism Disorders, Lysosomal Storage Diseases, Metabolic Diseases, Metabolic Inborn Brain Diseases, Metabolism, Inborn Errors, Metachromatic Leukodystrophy (MLD), Nervous System Diseases, Sphingolipidoses, Sulfatidosis
Conditions
Brief summary
The purpose of this study is evaluate the natural course of disease progression related to gross motor function in children with metachromatic leukodystrophy (MLD).
Detailed description
Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A (ASA). MLD is a rare genetic disease that occurs in most parts of the world. The estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births. This study is a multicenter, observational, longitudinal study that plans to enroll up to 30 patients with onset of MLD-related signs and symptoms prior to 30 months of age and who are less than 12 years of age. Patients will participate in this study for approximately 114 weeks (Screening through Follow-up) and will be assessed at defined intervals for disease status.
Interventions
None listed
Sponsors
Shire
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of MLD by both: * arylsulfatase A (ASA) deficiency by assay in leukocytes AND * elevated sulfatide in urine 2. Appearance of the first symptoms of disease at or before 30 months of age. 3. A GMFM-88 total (percent) score greater than or equal to 40 at the screening examination. 4. The patient is less than 12 years of age at the time of enrollment. 5. The patient and his/her parent or legally authorized representative(s) must have the ability to comply with the clinical protocol. 6. Patient's parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the patient.
Exclusion criteria
1. History of hematopoietic stem cell transplantation. 2. The patient has any known or suspected hypersensitivity to agents used for anesthesia or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions. 3. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study. 4. The patient is enrolled in another clinical study that involves the use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of this study is the change from baseline in motor function using the GMFM-88 total (percent) score. | Week 0 to Week 104 |
Secondary
| Measure | Time frame |
|---|---|
| The change from baseline in ability to swallow as assessed by the Functional Endoscopic Evaluation of Swallowing. | Week 0 to Week 104 |
| The change from baseline in nerve conduction as measured by the electroneurography. | Week 0 to Week 104 |
| Reporting of any study procedure-related nonserious AEs and/or any SAEs | Week 0 to Week 114 |
| The change from baseline in domain-specific Caregiver Observed MLD Functioning and Outcomes Reporting Tool. | Week 0 to Week 104 |
| The change from baseline in cognitive function using the Mullen Scales of Early Learning. | Week 0 to Week 104 |
| The change from baseline in the adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales. | Week 0 to Week 104 |
Countries
Argentina, Belgium, Brazil, Canada, Denmark, France, Germany, Japan, Turkey (Türkiye), United States
Outcome results
None listed