Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase

Study Overview
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Brief Summary
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Study TKT024EXT was a long-term, single-arm, open-label extension of Study TKT024, a one year Phase 2/Phase 3 registration study. The primary objective of this extension study was to collect long-term safety and clinical outcome data in Mucopolysaccharidosis II (MPS II), also known as Hunter Syndrome, from the Phase 2/Phase 3 Study TKT024. All patients enrolling into this study received weekly active treatment with idursulfase, the primary dosing regimen investigated in Study TKT024. Hunter Syndrome is an X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase, an enzyme required to catabolize glycosaminoglycans (GAGS) in cells. As a result, GAGs accumulate in the lysosomes leading to cellular engorgement, organomegaly, tissue destruction, and organ system dysfunction. Hunter Syndrome is a rare disease with an estimated incidence of 1 in 162,000 live births.

Detailed Description
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Study TKT024EXT was conducted in 2 phases. The first phase (Phase I) was 2 years (104 weeks) in duration and consisted of weekly infusions of IV idursulfase (0.5 mg/kg), and the collection of patients' safety and clinical outcomes. Week 105 defined the beginning of the second phase of the study. The second phase (Phase II) consisted of weekly infusions of IV idursulfase (0.5 mg/kg) and the monitoring of patients for safety (via collection of adverse events, concomitant medications, and vital signs). Study completion was defined as the time a patient either transitioned to commercially available idursulfase or discontinued this study. 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). Final evaluations from Study TKT024, the one-year predecessor Phase 2/Phase 3 registration study, served as the baseline assessments for the TKT024EXT study. Forced vital capacity (FVC) and the 6-minute walk test (6MWT) continued to be the primary clinical outcomes of TKT024EXT study. Efficacy outcomes were evaluated over the course of 2 years and 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 outcomes were assessed throughout the duration of the study. The safety and clinical testing performed in the TKT024EXT study were identical to those performed in the double-blind phase of Study TKT024.

Official Title
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An Open-Label Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Iduronate-2-Sulfatase Enzyme Replacement Therapy

Conditions
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Hunter Syndrome, Mucopolysaccharidosis II (MPS II)

Intervention / Treatment
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* Biological: Idursulfase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have completed the double-blind phase of Study TKT024, defined as completing the Week 53 final evaluations. 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. Exclusion Criteria: Patient has received treatment with an investigational therapy other than iduronate-2-sulfatase 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.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idursulfase<br> | Biological: Idursulfase<br>* Solution for intravenous infusion, 0.5 mg/kg once-weekly<br>* Other names: iduronate-2-sulfatase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105 | Determined by spirometry. The change is calculated as Week 105 minus baseline. | Baseline and at Week 105 | 
| Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105 | Determined on a walking course. The change was calculated as Week 105 minus baseline. | Baseline and at Week 105 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105 | Change was calculated as Week 105 minus baseline. Global JROM (% normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (DIP) motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association). | Baseline and at Week 105 | 
| Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105 | Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline. | Baseline and at Week 105 | 
| Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105 | Determined by urine testing. The change was calculated as Week 105 minus baseline. | Baseline and at Week 105 | 
| Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105 | Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change was calculated as Week 105 minus baseline. | Baseline and at Week 105 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hunter syndrome, hunters syndrome, hunter's syndrome, hunter disease, hunters disease, hunter's disease, MPS II, MPSII, MPS2, MPS 2, mucopolysaccharides, lysosomal storage disease, lysosomal storage disorder, chronic ear infection, enlarged adenoids, mps symptoms, mps diagnosis, mps ii therapy, MPS II treatment, ert treatment, elaprase, idursulfase, iduronate sulfatase, iduronate 2 sulfatase, enzyme replacement therapy, hunter syndrome treatment, hunter's syndrome treatment, hunter syndrome therapy, hunter's disease treatment, mps society