MPS IIIA Sanfilippo syndrome Type A
Conditions
Interventions
In the HGT-SAN 055 study patients have received an surgically implanted
intrathecal drug delivery device (IDDD) where they received 6 months of enzyme
therapy. Patients will continue monthly inthrat
Sponsors
Shire
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be considered eligible for enrollment: 1. The patients must have completed Study HGT-SAN-055 and, in the opinion of the investigator, has no safety or medical issues that contraindicate participation. 2. The patient, patient*s parent(s), or legally authorized representative has voluntarily signed an Institutional Review Board / Independent Ethics Committee-approved informed consent (and assent, if applicable) form after all relevant aspects of the study have been explained and discussed with the patient, patient*s parent(s), or legally authorized representative's consent and patient*s assent, as appropriate, must be obtained prior to any study specific procedures. 3. The patient has received at least 5 of the 6 planned infusions of rhHNS in the study HGT-SAN-055 study. 4. Patients must be medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel, assessments, and IDDD surgery (if necessary for replacement purposes), without placing an undue burden on the patient/patient's family.
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or at anytime during the study: 1. The patient has experienced an adverse reaction to study drug in Study HGT-SAN-055 that contraindicates further treatment with rhHNS. 2. The patient has a known hypersensitivity to the active ingredient or any excipients in rhHNS drug product. 3. 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. 4. The patient has significant MPS IIIA behavioral-related issues, as determined by the Investigator, which would preclude performance of study neurocognitive and developmental testing procedures. 5. 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, such as condoms, barrier method, oral contraception, etc. 6. 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. 7. The patient has a history of poorly controlled seizure disorder. 8. 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. 9. 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. 10. The patient has received treatment with any investigational drug (other than rhHNS) 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). 11. The patient has received a hematopoietic stem cell or bone marrow transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • To determine the longterm 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), 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 longterm effects of IT administration of rhHNS • 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 inflammatory cytokines in serum and CSF untill amendment 6. Concentration of rhHNS in CSF and serum • 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 untill month 54, auditory brainstem response (ABR), aka Brainstem Auditory Evoked Potentials | — |
Countries
Netherlands
Outcome results
None listed