MPS IIIA Sanfilippo syndrome Type A
Conditions
Interventions
At the start of the study patients will receive a surgically implanted
intrathecal drug
delivery device (IDDD). After this patients will receive Monthly or EOW
inthrathecal enzyme therapy.
Sponsors
Shire
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. a.)Patients have a documented deficiency in sulfamidase enzyme activity of *10% of the lower limit of the normal range as measured in fibroblasts or leukocytes (based on measurements by a laboratory that is acceptable to Shire HGT).
 AND EITHER b or C
 b.)Patients have a normal enzyme activity level of at least 1 other sulfatase (to rule out multiple sulfatase deficiency) as measured in fibroblasts or leukocytes (based on measurements by a laboratory that is acceptable to Shire HGT).
 c.) Patients have 2 documented mutations (based on assessments by a laboratory that is acceptable to Shire HGT).
 2. The patient is *3 years of age and has a developmental age above 1 year (developmental age will be determined by the screening neurocognitive and developmental tests).
 3. Patients must be medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel, assessments, and IDDD surgery, without placing an undue burden on the patient/patient's family.
 4. The patient*s parent(s) or legal guardian must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form
Exclusion criteria
Exclusion criteria: 1. The patient has 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 patient has MPS IIIA behavioral-related issues, as determined by the Investigator that would preclude performance of study neurocognitive and developmental testing procedures.
 3. The patient is pregnant, breast feeding, or is a female patient of childbearing potential who will not or cannot comply with the use of an acceptable method of birth control
 4. The patient is blind and/or deaf
 5. The patient has any known or suspected hypersensitivity to anesthesia or is thought to have an unacceptably high risk for anesthesia due to airway compromise or other conditions.
 6. The patient or the patient's family has a history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
 7. The Investigator may choose to exclude patients who have had complications resulting from prior lumbar punctures.
 8. The patient has a CNS shunt.
 9. The patient has skeletomuscular/spinal abnormalities or other contraindications for the surgical implantation of the IDDD.
 10. The patient has a history of poorly controlled seizure disorder.
 11. The patient is currently receiving psychotropic or other medications, which in the Investigator*s opinion, would be likely to substantially confound test results and the dose and regimen of which cannot be kept constant throughout the study.
 12. The patient cannot sustain absence from aspirin, non-steroidal medications, or medications that affect blood clotting within 1 week prior to a relevant study-related procedure (eg, device implantation if applicable), or has ingested such medications within 1 week before any procedures in which any change in clotting activity would be deleterious.
 13. The patient has received treatment with any investigational drug or a device intended as a treatment for MPS IIIA within the 30 days prior to, or during the study, or is currently enrolled in another study that involves an investigational drug or device (screening through safety follow-up contact).
 14. The patient has received a hematopoietic stem cell or bone marrow transplant.
 15. The patient*s parent(s), or patient*s legal guardian(s) is/are unable to provide consent or the patient cannot provide assent,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * To determine the safety of intrathecal rhHNS administration, as measured by adverse events (by type and severity), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis), electrocardiograms, CSF chemistries (including cell counts and inflammatory markers), and anti-rhHNS antibodies (in CSF and serum). | — |
Secondary
| Measure | Time frame |
|---|---|
| * To determine (by dose group) the effects of IT administration of rhHNS, as measured by (1) change from baseline values, and (2) comparison to values obtained in a longitudinal, 12-month, natural history study of untreated patients with MPS IIIA in the Shire HGT-SAN-053 Surrogate Endpoint Trial, on the following measurements/ assessments over a 6-month period: * Standardized neurocognitive and behavioral assessments as measured by the Bayley Scales of Infant Development, Third Edition (BSID-III), and the Kaufman Assessment Battery for Children, Second Edition (KABC-II). * Sanfilippo-specific behavioral rating scales, as measured by the Four-Point Scoring System/Total Disability Score (FPSS/TDS) and the Sanfilippo Behavioral Rating Scale (SBRS). * Gross and fine motor skills assessment and voluntary movement, as measured by the Movement Assessment Battery for Children, Second Edition (MABC-2). * Functional adaptive behavior as measured by the Vineland Adaptive Behavioral Scales, Second Edition (VABS-II). * Quality of life (QoL), as measured by the Child Health Questionnaire* Parent Form 50 (CHQ-50) Questions and Child Health Questionnaire* Child Form 87 (CHQ-87), Infant Toddler Quality of Life Questionnaire* (ITQOL), and Children*s Sleep Habits Rating Scale. * Concentration of rhHNS in CSF and serum. * Concentration of inflammatory cytokines in serum and CSF. * Concentration of heparan sulfate and heparan sulfate derivatives in urine and CSF, and, if possible, in serum. * Concentration of exploratory biomarkers in CSF, serum, and urine (potential surrogate markers of efficacy). * Brain magnetic resonance imaging (MRI) and auditory brainstem response (ABR), aka Brainstem Auditory Evoked Potentials. | — |
Countries
Netherlands
Outcome results
None listed