• Measurements of the six-minute-walk test (6-MWT) and forced vital capacity (FVC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Collection of adverse events (including infusion-related adverse events), and changes in 12-lead ECG, vital signs, physical exams, standard laboratory parameters, and anti-idursulfase antibody status. [ Time Frame: 2+ years ] [ Designated as safety issue: Yes ]

• Measurements of joint range of motion (JROM) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Measurements of combined liver and spleen size [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Measurements of urine GAG levels [ Time Frame: 2+ years ] [ Designated as safety issue: No ]
• Measurements of cardiac left ventricular mass (LVM) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Study TKT024EXT was a long-term, single-arm, open-label extension of Study TKT024. The primary objective of this extension study was to collect long-term safety and clinical outcome data in MPS II from Study TKT024. All patients enrolling into this study received weekly active treatment with idursulfase, the primary dosing regimen investigated in Study TKT024.

Study TKT024EXT was conducted in 2 phases. The first phase consisted of a 2-year period with each year consisting of 52 weekly infusions of idursulfase. Idursulfase was administered to patients as a continuous IV infusion at a dose of 0.5 mg of protein per kg of body weight (0.5 mg/kg). Certain final evaluations from Study TKT024 served as the baseline assessments for this study. Safety and efficacy outcomes were determined at 4-month intervals during the first year (ie, Weeks 18, 36, and 53) and at 6-month intervals in the second year (ie, Weeks 79 and 105). Safety and clinical outcomes were identical to those evaluated in the double-blind phase of Study TKT024. Forced vital capacity (FVC) and the 6-minute walk test (6MWT) continued to be the primary clinical outcomes of this study. Data were also collected on significant clinical events that reflect disease progression in this patient population. The focus was on events involving the major organ systems affected by MPS II: cardiac, respiratory, skeletal, and neurological.

The second phase of the study consisted of weekly infusions of IV idursulfase 0.5 mg/kg and monitoring patients for safety (via collection of adverse events, concomitant medications, and vital signs). Patients continued treatment during the second study phase until they transitioned to commercially available idursulfase or they discontinued this study for other reasons. Study completion was defined as the time a patient either transitioned to commercially available idursulfase or discontinued this study for other reasons.

Week 105 defined the beginning of the second study phase. Patients had a scheduled evaluation every 6 months until they completed or discontinued the study, including a safety evaluation (assessment of adverse events, concomitant medications, physical examination, clinical laboratory values, and anti-idursulfase antibodies), measurement of urine GAG levels, and collection of long-term clinical events. At the time a patient completed or discontinued the study, the patient should have had an "End of Study" evaluation consisting of assessment of adverse events, concomitant medications, 12-lead electrocardiogram (ECG), physical examination (including measurement of height, weight, and head circumference), clinical laboratory evaluations (including measurement of anti-idursulfase antibodies), measurement of urine GAG levels, and collection of long-term clinical events. In addition, patients who discontinued this study for reasons other than transitioning to commercially available idursulfase had an additional safety assessment 30 days after their last infusion.

To fulfill the secondary objective of this study, a commercial-scale manufacturing lot of idursulfase was introduced into the trial as soon as it was available, in order to begin generating safety data on this drug product. Pharmacokinetic (PK) data on this commercial-scale material was also obtained from the PK studies conducted during the first year of the study.

Initially, patients continued to receive their weekly infusions at the same study centers as in Study TKT024. However, based on an acceptable safety experience, patients were transitioned to investigational centers closer to their homes to receive their infusions. During the first phase of this study, patients were required to return to the main testing sites every 4 months during the first year and every 6 months during the second year for their major study evaluations. During the second phase, patients received their infusions and had all scheduled evaluations at the local clinical sites.

• Hunter Syndrome
• Mucopolysaccharidosis II

• Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. Epub 2006 Dec 20.
• Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. Erratum in: Genet Med. 2006 Sep;8(9):599. Wendt, Suzanne [corrected to Wendt, Susanne]; Puga, Antonio [corrected to Puga, Ana Cristina]; Conway, Ann Marie [corrected to Conway, Anne Marie].

Inclusion Criteria:

• Patient must have completed the double-blind phase of Study TKT024, defined as completing the Week 53 final evaluations of the study.
• Patient, patient's parent(s), or legally authorized representative 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, according to the local study site requirements.

Exclusion Criteria:

• Patient has received treatment with an investigational therapy other than the study drug in Study TKT024 within the past 60 days.
• 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.
• Patient has experienced an adverse reaction to study drug in Study TKT024, which contraindicates further treatment with idursulfase.
• Patient with known hypersensitivity to any of the components of idursulfase.