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 FunctionClassification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD.
- Conditions
- ate Metachromatic Leukodystrophy (MLD)MedDRA version: 20.0Level: PTClassification code 10067609Term: Metachromatic leukodystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-003291-12-IT
- 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
- All
- Target Recruitment
- 42
FOR COMPLETE LIST REFER TO PROTOCOL
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-E)
a. Low ASA activity in leukocytes (compared to laboratory normal range)
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: =6 to <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; younger siblings of enrolled subjects, and have the same ASA
allelic constitution
¿ Group E: GMFC-MLD level of 1 or 2 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
Inclusion criteria for matched historical controls: 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 (compared to laboratory normal range)
AND
b. Elevated sulfatides in urine
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 (±2) 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 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:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
FOR COMPLETE LIST REFER TO PROTOCOL
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 half-lives (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 patient has had, or may have, an allergic reaction to the materials of construction
b. The patient has shown an intolerance to an implanted device
c. The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port
d. The patient’s drug therapy requires substances known to be incompatible with the materials of
construction
e. The patient has a known or suspected local or general infection
f. The patient is at risk of abnormal bleeding due to a medical condition or therapy
g. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
h. The patient 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