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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 96
- 试验地点
- 16
- 主要终点
- Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 5 Years 至 25 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:
- •The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
- •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
- •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).
- •Must be male, 5 to 25 years of age.
- •Forced vital capacity of <80% of predicted obtained at the baseline evaluation of this study.
- •Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.
- •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.
排除标准
- •Patients meeting any of the following criteria are not eligible for participation in this study:
- •Patient has received treatment with another investigational therapy within the past 60 days.
- •Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
- •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 a tracheostomy.
- •Patient has received a bone marrow or cord blood transplant.
- •Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.
结局指标
主要结局
Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
时间窗: Baseline, Week 53
The 2-component composite variable consists of the sum of the ranked changes from baseline to Week 53 for percent predicted Forced Vital Capacity (FVC) and 6-Minute Walking Test (6MWT) total distance walked. For the 2 treatment groups being compared, ranking occurred within the comparison treatment groups combined (idursulfase weekly and placebo treatment groups). These comparison groups were pooled and ranked for each component separately. Within each component (% predicted FVC, 6MWT), the change from baseline was then ranked. The lowest change value was assigned a rank of 1, the next lowest a rank of 2, etc. The composite score for each participant was the sum of the 2 ranked scores corresponding to the 2 individual components (% predicted FVC and 6MWT) for each participant. Thus, the greater the composite score (greater the sum of the ranks of the changes from baseline, where the lowest change was ranked as 1), the greater the improvement.
次要结局
- Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53(Baseline, Week 53)
- Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53(Baseline, Week 53)
- Mean Combined Liver and Spleen Volume at Baseline(Baseline)
- Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53(Baseline, Week 53)
- Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline(Baseline)
- Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53(Baseline, Week 53)