Research study to determine the effects of an investigational drug, SHP611 on patients with with Late Infantile Metachromatic Leukodystrophy (MLD) specially the gross motor function, using the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD.

Phase 1

Conditions: ate Metachromatic Leukodystrophy (MLD)
MedDRA version: 20.0 Level: PT Classification code 10067609 Term: Metachromatic leukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2018-003291-12-DE

Lead Sponsor: Shire Human Genetic Therapies, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 42

Inclusion Criteria

Patients must meet all of the following criteria to be considered eligible for
inclusion as a subject in the study:

1. The subject must have a documented diagnosis of MLD (Groups A-D)
a. Low ASA activity in leukocytes
AND
b. Elevated sulfatides in urine

2. The subject 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 =6 to <18 months of age (Group D), or be early symptomatic and =12 to <18 months of age (Group E). Subjects in Group E must have neurological symptoms documented by a pediatric neurologist or medical geneticist.

3. The subject’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: <18 months of age
? Group E: =12 to <18 months of age
? Group F: 18 to 72 months of age

4. The subject’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 subjects, and have the same ASA allelic constitution
?Group E: early symptomatic, =12 to <18 months of age with a GMFCMLD 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

5. The subject and his/her parent/representative(s) must have the ability to comply with the clinical protocol

6. Subject'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 subject

Subjects must meet all of the following criteria to be considered eligible for inclusion as a matched historical control:

1. The subject must have a documented diagnosis of MLD
a. Low ASA activity in leukocytes
AND
b. Elevated sulfatides in urine

2. Subjects must have a gait disorder due to spastic ataxia or weakness attributed to MLD by the investigator and documented by 30 months of age

3. Subjects 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. Subjects 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

4. Subjects must be 18 to 48 months of age at the earliest assessment
Are the trial subjects under 18? yes
Number of subjects for this age range: 42
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range

Exclusion Criteria

1. 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

2. 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

3. Primary presentation of MLD was behavioral or cognitive symptoms (per investigator's clinical judgment); behavioral symptoms that are secondary to motor deficits (eg: tantrums in response to loss of motor skills) are not exclusionary.

4. The subject has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise 5. Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study

6. Subjects 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.

7. The subject is enrolled in another clinical study that involves use of any investigational product (drug or device) within 30 days or 5 halflives (whichever is longer) prior to study enrollment or at any time during the study

8. The subject has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use
a. The subject has had, or may have, an allergic reaction to the materials of construction
b. The subject has shown an intolerance to an implanted device
c. The subject's body size is too small to support the size of the SOPH-APORT Mini S Access Port
d. The subject's drug therapy requires substances known to be incompatible with the materials of construction
e. The subject has a known or suspected local or general infection
f. The subject is at risk of abnormal bleeding due to a medical condition or therapy
g. The subject has one or more spinal abnormalities that could complicate safe implantation or fixation
h. The subject has a functioning CSF shunt device

Exclusion criteria for matched historical controls:
1. 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
2. Primary presentation of MLD was behavioral or cognitive symptoms (per investigator's clinical judgment); behavioral symptoms that are secondary to motor deficits (eg; tantrums in response to loss of motor skills) are not exclusionary.
3. The subject is enrolled in another clinical study that involves use of any investigational product (drug or device)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials