Sanfilippo Syndrome Type A or Mucopolysaccharidosis (MPS IIIA) MedDRA version: 17.1 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 17.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Shire Human Genetic Therapies, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be considered eligible for enrollment: 1. Documented MPS IIIA diagnosis: a) All patients must show a documented deficiency in sulfamidase enzyme activity consistent with a diagnosis of MPS IIIA AND b) Patients must show documented mutations in each SGSH allele OR there must be documentation of mutations in each SGSH allele in a sibling affected by MPSIIIA, provided parental consent is obtained to use this information. 2. Age =12 months and = 48 months 3. The patient has a DQ score =60%, assessed by cognitive evaluation at screening assessment using the BSID-III 4. The patient is medically stable, in the opinion of the Investigator, and able to accommodate the protocol requirements, including travel, assessments, and IDDD surgery, without placing an undue burden on the patient/patient's family 5. The patient’s parent(s) or legal guardian must have voluntarily signed an Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient’s parent(s), or legal guardian. Consent of the patient’s parent(s) or legally authorized guardian(s) must be obtained prior to the start of any study procedures. Are the trial subjects under 18? yes Number of subjects for this age range: 18 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
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if any of the following criteria are met at screening: 1. The presence of significant non-MPS IIIA related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific integrity or interpretation of study assessments, as determined by the Investigator. 2. The presence of at least one S298P mutation in SGSH, associated with attenuated disease OR there is documentation of the S298P mutation in a sibling affected by MPS IIIA, provided parental consent is obtained to use this information. 3. The presence of relatively attenuated MPS IIIA disease in an older sibling, defined as preservation of any comprehensible speech beyond the age of 10 years 4. Visual or hearing impairment, in the clinical judgement of the investigator, sufficient to preclude cooperation with neurodevelopmental testing. 5. In the opinion of the Investigator, the patient is assessed as having an unacceptably high risk for anesthesia due to airway compromise, drug hypersensitivity, or other conditions (such as neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns). 6. The patient has a history of poorly controlled seizure disorder. 7. The patient is currently receiving psychotropic or other medications, which in the Investigator’s opinion would be likely to substantially confound test results. 8. The patient has a history of bleeding disorder or is unable to abstain from medications that, in the opinion of the investigator, place them at risk of bleeding following surgery or lumbar puncture.. 9. The patient participated in a clinical trial of another investigational medicinal product, within the 30 days prior to the study (or within 5 elimination half lives of the investigational product), or is currently enrolled in another study that involves an investigational drug or device. NOTE: Nutritional supplements, including genistein are permitted if they are taken or administered outside the context of a formal investigation. 10. The patient has received a hematopoietic stem cell or bone marrow transplant, or gene therapy. 11. The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including: a) The patient has had an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device b) The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator c) The patient has a known or suspected local or general infection d) The patient has one or more spinal abnormalities that could complicate safe implantation or fixation e) The patient has a functioning CSF shunt device f) The patient has shown an intolerance to an implanted device 12. The patient’s parent(s) or patient’s legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study, or do/does not agree to comply with the protocol defined schedule of assessments. 13. The patient is unable to comply with the protocol (eg, has a clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the Investigator, otherwise unsuited for the study. 14. The patient has any item (braces, tattoos, etc.) which would exclude the patient from being able to undergo MRI according to local Institutional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the potential clinical efficacy of HGT-1410 administered via a surgically implanted IDDD in patients with Sanfilippo Syndrome Type A (MPS IIIA). Efficacy will be measured as a meaningful amelioration in the progression of cognitive decline, and will be measured using the Bayley Scales of Infant Development, 3rd Edition (BSID III).;Secondary Objective: To determine the following: the safety and tolerability of HGT-1410 IT; the effect of HGT-1410 administration on BSID-III age-equivalent and DQ scores; the effect of HGT-1410 IT on adaptive behavioral function, assessed by Vineland Adaptive Behavior Scales, Second Edition (VABS-II); the effect of HGT-1410 IT treatment on the total cortical grey matter volume, as assessed by volumetric MRI of the brain; the effect of HGT-1410 IT treatment on the concentration of GAG in CSF and urine; and the pharmacokinetics of HGT-1410 in cerebrospinal fluid (CSF) and serum.;Primary end point(s): Achievement of response, defined as a maximum decline in cognitive DQ of 10 points over 48 weeks, as assessed by the Bayley Scales of Infant Development, 3rd Edition.;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety endpoints including the assessment of adverse events (AEs), IDDD related issues, laboratory values, anti-rhHNS antibody development, vital signs, physical examination findings, and ECG results • The change from baseline to Week 48 in adaptive behavioral function, assessed by VABS II, using raw scores and age equivalent score • The change from baseline to Week 48 in the DQ assessed by neurocognitive testing, using the BSID-III age equivalent scores • The change from Baseline to Week 48 in total cortical grey matter volume, as assessed by MRI • The change from Baseline to Week 48 in concentrations of GAG in the CSF and urine • The concentration of HGT-1410 in CSF and serum;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Countries
Argentina, Brazil, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactKenia Baez
Shire Human Genetic Therapies Inc
Outcome results
None listed