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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 94
- 试验地点
- 102
- 主要终点
- Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105
时间窗: Baseline and at Week 105
Determined by spirometry. The change is calculated as Week 105 minus baseline.
Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105
时间窗: Baseline and at Week 105
Determined on a walking course. The change was calculated as Week 105 minus baseline.
次要结局
- Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105(Baseline and at Week 105)
- Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105(Baseline and at Week 105)
- Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105(Baseline and at Week 105)
- Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105(Baseline and at Week 105)