A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Early Stage Mucopolysaccharidosis Type IIIA Disease
- Conditions
- mucopolysaccharideSanfilippo syndrome10000546
- Registration Number
- NL-OMON40318
- Lead Sponsor
- Shire
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Documented MPS IIIA diagnosis:
a) All patients must show a documented deficiency in sulfamidase
enzyme activity of *10% of the lower limit of the normal range as
measured in fibroblasts or leukocytes
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 Developmental Quotient score *60%, assessed by
cognitive evaluation at screening assessment using the Bayley Scales of
Infant and Toddler Development *3rd Edition (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, and 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.
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 the S298P mutation in either or both SGSH alleles,
associated with attenuated disease 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.
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-APORT
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 i
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Achievement of response, defined as a maximum decline in cognitive DQ of 10<br /><br>points<br /><br>over 48 weeks, as assessed by the Bayley Scales of Infant Development, 3rd<br /><br>Edition.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Safety endpoints including the assessment of adverse events (AEs), IDDD<br /><br>related<br /><br>issues, laboratory values, anti-rhHNS antibody development, vital signs,<br /><br>physical<br /><br>examination findings, and ECG results<br /><br>-The change from baseline to Week 48 in adaptive behavioral function, assessed<br /><br>by<br /><br>VABS II, using raw scores and age equivalent score<br /><br>- The change from baseline to Week 48 in the DQ assessed by neurocognitive<br /><br>testing, using the BSID-III age equivalent scores<br /><br>- The change from Baseline to Week 48 in total cortical grey matter volume, as<br /><br>assessed by MRI<br /><br>- The change from Baseline to Week 48 in concentrations of GAG in the CSF and<br /><br>urine<br /><br>- The concentration of HGT-1410 in CSF and serum</p><br>