Clinical Trials

Inclusion Criteria:

• The participant must have a documented diagnosis of MLD (Groups A-F):
  • Low ASA activity in leukocytes (compared to laboratory normal range);
  • Elevated sulfatides in urine. 
• The participant must have a gait disorder due to spastic ataxia or weakness attributed to MLD by the investigator and documented by a pediatric neurologist or medical geneticist by 30 months of age (Groups A-C, and F), or be minimally symptomatic and greater than or equal to (≥) 6 to less than (<) 18 months of age (Group D), or be early symptomatic and ≥ 12 to < 18 months of age (Group E). Participants in Group E must have neurological symptoms documented by a pediatric neurologist or medical geneticist. 
• The participant's age at the time of informed consent, must be:
  • Group A: 18 to 48 months of age;
  • Group B: 18 to 72 months of age;
  • Group C: 18 to 72 months of age;
  • Group D: ≥ 6 to < 18 months of age;
  • Group E: ≥ 12 to < 18 months of age;
  • Group F: 18 to 72 months of age. 
• The participant's GMFC-MLD level at screening must be:
  • Group A: GMFC-MLD level of 1 or 2;
  • Group B: GMFC-MLD level of 3;
  • Group C: GMFC-MLD level of 4;
  • Group D: minimally symptomatic, > 6 to < 18 months of age, younger siblings of enrolled participants, and have the same arylsulfatase (ASA) allelic constitution;
  • Group E: early symptomatic, ≥ 12 to < 18 months of age with a GMFC-MLD level of 1 or 2, and with a history of achieving stable walking (defined as at least 1 month of independent walking);
  • Group F: GMFC-MLD level of 5 or 6.
• The participant and his/her parent/representative(s) must have the ability to comply with the clinical protocol. 
• Participant'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 participant.

Inclusion Criteria for Matched Historical Controls: 

• The participant must have a documented diagnosis of MLD:
  • Low ASA activity in leukocytes (compared to laboratory normal range);
  • Elevated sulfatides in urine. 
• Participants must have a gait disorder due to spastic ataxia or weakness attributed to MLD by the investigator and documented by 30 months of age. 
• Participants must have at least 2 motor assessments by GMFC-MLD with the second assessment occurring at approximately 106 (+/-2) weeks after the first assessment or else a second assessment measured before Week 100 with a GMFC-MLD level 5 or 6.
• Participants with GMFC-MLD data (pro or retrospectively determined) must have the earliest observation of level 1 or 2 (walking with support) in the data source-verified medical record. 
• Participants must be 18 to 48 months of age at the earliest assessment.

Exclusion Criteria: 

• Multiple sulfatase disorder as determined by abnormal activity of another lysosomal sulfatase (based upon the reference laboratory's normal range) or a known genetic disorder other than MLD. 
• History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy or undergoes BMT, HSCT, or gene therapy at any point during the study. 
• Primary presentation of MLD was behavioral or cognitive symptoms (per investigator's clinical judgment); behavioral symptoms that are secondary to motor deficits (e.g., tantrums in response to loss of motor skills) are not exclusionary.
• The participant has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise. 
• Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study.
• Participants with laboratory, ECG or vital sign abnormalities reflecting intercurrent illness that may compromise their safety during the trial should not be enrolled. Abnormal laboratory, vital sign and ECG results at screening should be reviewed with the Shire medical monitor. 
• The participant is enrolled in another clinical study that involves use of any investigational product (drug or device) within 30 days or 5 half-lives (whichever is longer) prior to study enrollment or at any time during the study. 
• The participant has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use (IFU):
  • The participant has had, or may have, an allergic reaction to the materials of construction; 
  • The participant has shown an intolerance to an implanted device;
  • The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port;
  • The participant's drug therapy requires substances known to be incompatible with the materials of construction;
  • The participant has a known or suspected local or general infection;
  • The participant is at risk of abnormal bleeding due to a medical condition or therapy;
  • The participant has one or more spinal abnormalities that could complicate safe implantation or fixation;
  • The participant has a functioning Cerebro spinal fluid(CSF) shunt device.

Exclusion Criteria for Matched Historical Controls: 

• History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy or undergoes BMT, HSCT, or gene therapy at any point during the study. 
• Primary presentation of MLD was behavioral or cognitive symptoms (per investigator's clinical judgment); behavioral symptoms that are secondary to motor deficits (e.g., tantrums in response to loss of motor skills) are not exclusionary. 
• The participant is enrolled in another clinical study that involves use of any investigational product (drug or device).