| Purpose: |
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Elaprase, a large molecular protein, is not expected to cross the blood brain barrier when
administered intravenously. A revised formulation of idursulfase, idursulfase-IT, that
differs from that of the IV formulation, Elaprase, has been developed to be suitable for
delivery into the CSF via intrathecal administration.
This Phase I/II study is designed to obtain necessary safety and exposure data, as well as
secondary and exploratory outcome measures, to be interpreted and used in the design of
subsequent clinical trials.
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| Criteria: |
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Inclusion Criteria:
1a. A deficiency in iduronate-2-sulfatase enzyme activity of ≤10 % of the lower limit of
the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range
of measuring laboratory) AND
1b. A documented mutation in the iduronate-2-sulfatase gene OR A normal enzyme activity
level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on
normal range of measuring laboratory).
2. The patient is male and is ≥3 and <18 years of age .
3. The patient has evidence at Screening of early stage (duration and severity metrics per
protocol) Hunter syndrome-related CNS involvement, defined as:
- The patient has an IQ ≤77 OR
- There is evidence of a change of ≥1 but ≤2 standard deviations decline from a
previous protocol-defined neurodevelopmental assessment. The duration of
protocol-defined neurologic involvement is at least 3 months but less than 36 months
as documented in the patient's medical history.
4. The patient has received and tolerated a minimum of 6 months of treatment with
weekly intravenous idursulfase, and has received 80% of the total planned infusions
within that time frame, including having received 100% of the planned infusions
within 4 weeks immediately preceding the surgical insertion of the IDDD.
5. The patient must have sufficient auditory capacity, with or without aids, to
complete the required protocol testing, and be compliant with wearing the aid on
scheduled testing days.
6. The patient, patient's parent(s), or legally authorized guardian(s) must have
voluntarily signed an Institutional Review Board / Independent Ethics
Committee-approved informed consent form after all relevant aspects of the study have
been explained and discussed with the patient. The guardians' consent must be
obtained.
Exclusion Criteria:
1. The patient has clinically significant non-Hunter syndrome-related CNS involvement
which is judged by the Investigator to be likely to interfere with the accurate
administration and interpretation of protocol assessments.
2. The patient has an IQ ≥78
3. The patient has a CNS shunt.
4. The patient has experienced an infusion-related anaphylactoid event or has evidence
of consistent severe adverse events related to treatment with Elaprase which, in the
Investigator's opinion, may pose an unnecessary risk to the patient.
5. The patient has any known or suspected hypersensitivity to anesthesia or is thought
to be at an unacceptably high risk for anesthesia due to compromised airways or other
conditions
6. The patient has a history of complications from previous lumbar punctures or
technical challenges in conducting lumbar punctures such that the potential risks
would exceed possible benefits for the patient.
7. The patient or patient's family has a history of neuroleptic malignant syndrome,
malignant hyperthermia, or other anesthesia-related concerns.
8. The patient has a history of poorly controlled seizure disorder.
9. The patient has a significant medical or psychiatric comorbidity(ies) that might
affect study data or confound the integrity of study results.
10. The patient is currently receiving chronic psychotropic therapy (e.g., neuroleptics,
benzodiazepines, antidepressants, anticonvulsants, stimulants, etc.) which in the
Investigator's opinion would likely affect the neurocognitive assessments.
Intermittent use of selected short half-life agents (benzodiazepine, sedatives, etc.)
may be permitted as long as there are 5 half-lives between last drug administered and
study-related procedures including neurocognitive assessments.
11. The patient has received treatment with any investigational drug or device within the
30 days prior to study entry.
12. The patient has received a cord blood or bone marrow transplant at any time, or has
received blood product transfusions within 90 days prior to Screening.
13. The patient is unable to comply with the protocol, (e.g., has significant hearing or
vision impairment, a clinically relevant medical condition making implementation of
the protocol difficult, unstable social situation, known clinically significant
psychiatric/behavioral instability, is unable to return for safety evaluations, or is
otherwise unlikely to complete the study), as determined by the Investigator.
14. The patient has skeletomuscular/spinal abnormalities or other contraindications for
the surgical implantation of the IDDD.
15. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30 cm H2O. |