A Multi-Center, Open-Label Study Evaluating Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Enzyme Replacement Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 28
- 试验地点
- 3
- 主要终点
- Safety Evaluation
研究概览
简要总结
The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old.
详细描述
This study will provide a basis for evaluating the safety of idursulfase administered to Hunter syndrome patients who are ≤ 5 years old. Additionally, this study will provide a basis for evaluating the idursulfase single- and repeated-dose pharmacokinetic profiles as well as the pharmacodynamic effect (as measured by urinary GAG excretion) in this pediatric population. Additional exploratory measures will include abdominal ultrasound measurements of liver and spleen volumes, assessments of growth with comparisons to normal population growth data, assessments of annualized growth velocity, assessments of routine developmental milestones using the Denver II, and assessments of clinical events, including the first occurrence of certain hearing-related events (e.g., hearing loss, otitis media), respiratory-related events (e.g., upper and lower respiratory infections), and specific surgical procedures (e.g., adenoidectomy, placement of PE tubes).
All patients in this open-label study will receive once-weekly infusions of idursulfase at a dose of 0.5 mg/kg.
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
- — 至 5 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening:
- •A deficiency in iduronate-2-sulfatase (I2S) enzyme activity of ≤ 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).
- •The patient is 5 years of age and under.
- •The patient is male.
- •The patient's parent(s), or patient's legal guardian must have voluntarily signed an Institutional Review Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's parent(s), or the patient's legal guardian.
排除标准
- •The patient has received treatment with another investigational therapy within 30 days prior to enrollment.
- •The patient has clinically relevant medical condition(s) making implementation of the protocol difficult.
- •The patient has previously received idursulfase.
- •The patient has known hypersensitivity to any of the components of idursulfase.
- •The patient has had a tracheostomy.
研究组 & 干预措施
Idursulfase
Open-label treatment with idursulfase
干预措施: Idursulfase (Biological)
结局指标
主要结局
Safety Evaluation
时间窗: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported.
次要结局
- Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)(Weeks 1 and 27)
- Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels(Baseline, Weeks 18, 36 and 53)
- Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)(Weeks 1 and 27)
- Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)(Weeks 1 and 27)