Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)

A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients With MPS II

The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II.

MPS II is a rare, X-linked, lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Because of this deficiency, glycosaminoglycans (GAG) accumulate in multiple tissues and organs, resulting in progressive cellular and organ system dysfunction. The purpose of this study is to determine if one year of therapy with iduronate-2-sulfatase enzyme replacement therapy, at a dose of 0.5mg/kg, weekly or every other week, is safe, and results in clinically meaningful improvement in multiple organ function, compared with a placebo group. Upon completion of the study, patients will be eligible to enroll in an open-label maintenance study.

Inclusion Criteria:

To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:

1. The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.

2. All patients must have at least one of the following Clinical Criteria considered by the investigator to be MPS II-related:

   • Hepatosplenomegaly
   • Radiographic evidence of dysostosis multiplex
   • Valvular heart disease
   • Evidence of obstructive pulmonary disease

3. In addition, patients must have the following Biochemical Criteria:

   • Documented deficiency in iduronate-2-sulfastase enzyme activity of less than or equal to 10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
   • A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).

4. Must be male, 5 to 25 years of age.

5. Forced vital capacity of <80% of predicted obtained at the baseline evaluation of this study.

6. Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.

7. Patient, patient's parent(s), or legally authorized guardian must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for participation in this study:

1. Patient has received treatment with another investigational therapy within the past 60 days.
2. Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
3. Patient is unable to comply with the protocol (e.g., due to a medical condition such as cervical cord compression or uncooperative attitude) or is unlikely to complete the study, as determined by the investigator.
4. Patient has a tracheostomy.
5. Patient has received a bone marrow or cord blood transplant.
6. Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.