A Study of Intrathecal SHP611 in Participants With Late Infantile Metachromatic Leukodystrophy

Inclusion Criteria:

- The participant must have a documented diagnosis of metachromatic leukodystrophy (MLD)
(Groups A-D): a. low arylsulfatase A (ASA) activity in leukocytes; b. 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) or presymptomatic (Group D).

- 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: less than (<) 18 months of age.

- The participant's Gross Motor Function Classification in Metachromatic Leukodystrophy
(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: presymptomatic, are
younger siblings of enrolled participants, and have the same ASA allelic constitution.

- 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: a. low ASA activity in
leukocytes; b. elevated sulfatides in urine.

- Participant must have a gait disorder due to spastic ataxia or weakness attributed to
MLD by the investigator and documented at baseline.

- Participant must have at least 2 motor assessments by GMFC-MLD with the second
assessment occurring at approximately 106 (+/-6) weeks after the first assessment or
else a second assessment measured before week 100 with a GMFC-MLD level 5 or 6.
Participant 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.

- Participant 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).

- History of hematopoietic stem cell transplantation (HSCT) or gene therapy or undergoes
HSCT or gene therapy at any point during the study.

- Initial presentation of behavioral or cognitive symptoms of MLD (per investigator's
clinical judgment).

- 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.

- The participant is enrolled in another clinical study that involves use of any
investigational product (drug or device) within 30 days 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 intrathecal drug delivery device (IDDD) Instructions for Use (IFU).

Exclusion criteria for matched historical controls:

- History of hematopoietic stem cell transplantation (HSCT) or gene therapy or undergoes
HSCT or gene therapy at any point during the study.

- Initial presentation of behavioral or cognitive symptoms of MLD (per investigator's
clinical judgment).

- The participant is enrolled in another clinical study that involves use of any
investigational product (drug or device).