Sanfilippo Syndrome Type A or Mucopolysaccharidosis (MPS IIIA) MedDRA version: 19.1 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 19.1 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. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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 |
|---|---|
| Primary end point(s): To determine the long-term 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 (ECG), cerebrospinal fluid (CSF) chemistries (including cell counts and inflammatory markers), and anti-rhHNS antibodies (in CSF and serum).;Timepoint(s) of evaluation of this end point: 8.5 years (103 months);Main Objective: To collect long-term safety and tolerability data in patients with Sanfilippo Syndrome Type A (MPS IIIA) who received rhHNS via a surgically implanted intrathecal drug delivery device (IDDD) in study HGT-SAN-055 and elected to continue therapy.;Secondary Objective: To collect as measures of drug efficacy, over an extended treatment period (as change from baseline), the following: clinical, neurological, cognitive, behavioral, functional, and quality of life (QoL) assessments, together with potential imaging and biochemical biomarkers. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Standardized neurocognitive and behavioral assessments -Concentration of rhHNS in cerebrospinal fluid (CSF) and serum -Concentration of inflammatory cytokines in serum and CS-Concentration of safety and potential surrogate efficacy biomarkers in CSF, urine, and serum -Concentration of heparan sulfate and heparan sulfate derivatives in urine, plasma and serum -Brain magnetic resonance imaging (MRI) and auditory brainstem response (ABR), aka Brainstem Auditory Evoked Potentials.;Timepoint(s) of evaluation of this end point: 8.5 years (103 months) | — |
Countries
Netherlands, United Kingdom
Contacts
Public ContactAlkisti Rouvas
Shire Human Genetic Therapies Inc
Outcome results
None listed