Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment

Inclusion Criteria Inclusion Criteria for the Pivotal Study

Patients must meet all of the following criteria to be considered eligible for randomization in the pivotal study:

• The patient is male and is ≥3 and 85, there must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented test result in observational study HGT-HIT-090.

A patient who is ≥13 and <18 years of age must have both of the following criteria (3c AND 3d):

• A GCA score of ≥55 and ≤85. AND
• There must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented
• The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
• The patient must have sufficient auditory capacity, with a hearing aid(s), if needed, in the Investigator's judgment to complete the required protocol testing and must be compliant with wearing the hearing aid(s), if needed, on scheduled testing days.
• The 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. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, if applicable, must be obtained prior to the start of any study procedures.

Inclusion Criteria for the Substudy

Patients must meet all of the following criteria to be considered eligible for enrollment in the separate substudy:

• The patient is male and is <3 years of age at the time of informed consent.
• The patient must have a documented diagnosis of MPS II.
• The patient has evidence at Screening of Hunter syndrome-related cognitive impairment
• The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
• The patient must have sufficient auditory capacity, with a hearing aid(s), if needed, in the Investigator's judgment to complete the required protocol testing and must be compliant with wearing the hearing aid(s), if needed, on scheduled testing days.
• The 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. Consent of the patient's parent(s) or legally authorized guardian(s) must be obtained prior to the start of any study procedures.

Exclusion Criteria

Patients who meet any of the following criteria are not eligible to be randomized into the pivotal study or enrolled in the separate substudy:

• The patient has clinically significant non-Hunter syndrome-related CNS involvement (such as Fragile-X syndrome) which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.
• The patient has a large chromosomal deletion or complex rearrangement that includes a deletion of the FMR1 and/or FMR2 genes.
• The patient has a significant medical or psychiatric comorbidity(ies) that might affect study data or confound the integrity of study results.
• The patient has contra-indications for performance of lumbar puncture such as musculoskeletal/spinal abnormalities or risk of abnormal bleeding.
• 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.
• The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.
• The patient has experienced infusion-related anaphylactoid event(s) 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.
• The patient has