Resumen

El objetivo principal del estudio es determinar si SHP611 administrado mediante inyección en el líquido espinal que rodea el cerebro y la médula espinal (intratecal; IT) prolonga el tiempo durante el cual los niños con leucodistrofia metacromática (LDM) conservan la capacidad de desplazarse. Otros objetivos son determinar los efectos de la administración intratecal de SHP611 sobre las funciones motoras y del habla y evaluar la tolerabilidad de SHP611 inyectado en el líquido espinal. Los participantes recibirán SHP611 durante aproximadamente 2 años con posibilidad de un período de tratamiento extendido.

Elegibilidad

Edad mínima: 6 MonthsEdad máxima: 72 MonthsSexo: ALL

Criterios de inclusión

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 attributable to MLD by the investigator and documented by a primary care physician or a specialist physician 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 either documented by either a primary care physician or a specialist physician.
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 category at screening must be: Group A: GMFC-MLD category of 1 or 2; Group B: GMFC-MLD category of 3; Group C: GMFC-MLD category of 4; Group D: minimally symptomatic, \>= 6 to \< 18 months of age, with the same arylsulfatase (ASA) allelic constitution as an older sibling with confirmed late infantile or juvenile onset MLD; Group E: early symptomatic, \>= 12 to \< 18 months of age with a GMFC-MLD category of 1 or 2 with a history of achieving stable walking (defined as at least 1 month of independent walking); Group F: GMFC-MLD category 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.
A filtering process will be applied to select the external control participants from the GLIA-MLD database, by meeting all of the following 3 filtering criteria:
Filtering criterion 1: requiring documented diagnosis of MLD, based on
low arylsulfatase A (ASA) activity in leukocytes AND elevated sulfatides in urine. OR
biallelic variants in arylsulfatase A gene (ARSA) AND (either low ASA activity in leukocytes OR elevated sulfatides in urine).
Filtering criterion 2: requiring documented gait disorder. Participants will be considered qualifying if they present with a gait disorder before 2.5 years (30 months) of age and have a medical record reporting a gait abnormality including, but not limited to, the following terms: ataxia, spasticity, and hyper/hypotonia.
Filtering criterion 3: participants will be considered qualifying if they have at least 1 clinical encounter occurring between the age of 18 to 48 months with a GMFC-MLD category either 1 or 2.

Criterios de exclusión

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 (example \[eg\], 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 Takeda 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 had prior exposure to SHP611.
The participants must weigh \> 11 pound (lbs) (5 kilograms \[kg\]).
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 .

Estudio global, multicéntrico, de brazo único con control externo apareado de SHP611 intratecal en sujetos con leucodistrofia metacromática de inicio tardío en la infancia

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

SHP611

Ubicaciones

Hospital Universitario Austral - PIN

Patrocinadores