a study of intrathecal shp611 in children with metachromatic leukodystrophy

Conditions: Metachromatic Leukodystrophy (MLD)

Summary: the main aim of the study is to determine if shp611 given by injection into the spinal fluid that surrounds the brain and spinal cord (intrathecal; it) prolongs the time for children with metachromatic leukodystrophy (mld) to retain the ability to move from place to place. other aims of the study are to determine the effects of intrathecal administration of shp611 on movement and speech functions and to learn how well shp611 injected in the spinal fluid that surrounds the brain and spinal cord is tolerated. study participants will receive shp611 for about 2 years with the possibility of an extended treatment period.


Eligibility criteria:
inclusion criteria: * the participant must have a documented diagnosis of mld (groups a-f): 1. low asa activity in leukocytes (compared to laboratory normal range). 2. 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 (\ =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 \ = 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 \ = 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. 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 (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) 1. the participant has had, or may have, an allergic reaction to the materials of construction. 2. the participant has shown an intolerance to an implanted device. 3. the participant's body size is too small to support the size of the soph-a-port mini s access port. 4. the participant's drug therapy requires substances known to be incompatible with the materials of construction. 5. the participant has a known or suspected local or general infection. 6. the participant is at risk of abnormal bleeding due to a medical condition or therapy. 7. the participant has one or more spinal abnormalities that could complicate safe implantation or fixation. 8. the participant has a functioning cerebro spinal fluid(csf) shunt device . matched external control participants for group a from global leukodystrophy initiative of metachromatic leukodystrophy (glia-mld) the matched external control group must have data for at least baseline gross motor function evaluation. selection of the external control participants from glia-mld will follow a set of criteria as similar as possible to the inclusion criteria for group a in the shp611-201 study protocol. 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: 1. 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). 2. 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. 3. 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.