Clinical Study to Investigate the Efficacy, Pharmacokinetics, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease Patients Under the Age of 6 Years
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Total Annualised Bleeding Rate (TABR) During Prophylactic Treatment With Wilate.
研究概览
简要总结
The WIL-33 study aimed to determine the efficacy, pharmacokinetics, immunogenicity and safety of wilate as routine prophylaxis in up to 12 paediatric patients (eight evaluable) with severe von Willebrand Disease VWD (defined as screening von Willebrand factor ristocetin cofactor activity [VWF:RCo] <20%) under the age of 6 years, over a period of 12 months.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged <6 years at the time of screening
- •Type 3 (at least four patients), severe type 2 (except 2N) or severe type 1 VWD (any of which with VWF:RCo <20%) according to medical history, requiring substitution therapy with a VWF-containing product
- •Minimum BW 12.5 kg at the time of screening (for Moldova and Czech Republic, minimum BW 11.0 kg at the time of screening)
- •Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patient's parent(s) / legal guardian(s))
排除标准
- •History or current suspicion of VWF or FVIII inhibitors
- •Injection of 1-deamino-8-D-arginine vasopressin (DDAVP) or VWF-containing product within 72 hours prior to inclusion
- •Medical history of a thromboembolic event
- •Platelet count <100,000/µL at screening (except for VWD type 2B)
- •Patients receiving, or scheduled to receive, immunosuppressant drugs (other than antiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs
- •Treatment with any investigational medicinal product (IMP) in another interventional clinical study currently or within four weeks before enrolment
- •Other coagulation disorders or bleeding disorders
- •Known hypersensitivity to any of the components of the study drug
研究组 & 干预措施
Wilate treatment
PK: Single dose of 80 IU/kg body weight (BW). Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at recommended dose over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve von Willebrand factor activity (VWF:Ac) and Factor VIII coagulant activity (FVIII:C) trough levels of >30%. Major haemorrhage: loading dose 50-80 IU/kg BW then maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of >50%. Minor surgery: loading dose of 40-60 IU/kg BW then maintenance dose of 20-30 IU/kg BW every 12-24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels >30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW then a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels >50% during maintenance
干预措施: Wilate (Drug)
结局指标
主要结局
Total Annualised Bleeding Rate (TABR) During Prophylactic Treatment With Wilate.
时间窗: During 12 months of prophylactic treatment
TABR is defined as the total number of bleeding episodes (BEs) including spontaneous, traumatic, and other bleeds, occurring during the period from the first prophylactic dose of wilate to the study completion visit, divided by the duration (in years) between these two time points. Bleeding episodes that occurred during surgery periods were excluded from the calculation of TABR. Total BEs refers to all bleeding episodes that occurred during the study period, regardless of whether they were treated with wilate or not. Treated BEs are a subset of total BEs comprising of bleeding episodes that were treated with wilate.
次要结局
- Area Under the Curve (AUC) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Area Under the Curve (AUC) of Wilate for FVIII (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- AUC Normalised for the Administered Dose (AUCnorm) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- AUC Normalised for the Administered Dose (AUCnorm) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Clearance (CL) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Clearance (CL) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Maximum Plasma Concentration (Cmax) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Maximum Plasma Concentration (Cmax) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Mean Residence Time (MRT) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Mean Residence Time (MRT) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- In Vivo Half-life (T1/2) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- In Vivo Half-life (T1/2) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Time to Reach Maximum Plasma Concentration (Tmax) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Time to Reach Maximum Plasma Concentration (Tmax) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Volume of Distribution (Vd) of Wilate for VWF:Ac (VWF:RCo) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Volume of Distribution (Vd) of Wilate for FVIII:C (OS) Over Time(At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate)
- Incremental In-vivo Recovery (IVR) of Wilate for VWF:Ac (VWF:RCo) Over Time(Measures were taken at the following timepoints: baseline and 1, 2, 3, 6, 9, and 12 months of treatment with IVR values reported at baseline and 12 months.)
- Incremental In-vivo Recovery (IVR) of Wilate for FVIII:C (OS) Over Time(Measures were taken at the following timepoints: baseline and 1, 2, 3, 6, 9, and 12 months of treatment with IVR values reported at baseline and 12 months.)
- Efficacy of Wilate Measured by the Proportion of BEs Successfully Treated With Wilate(Up to 12 months of treatment)
- The Overall Efficacy of Wilate in Perioperative Prophylaxis Against Excessive Bleeding as Assessed at the End of the Postoperative Period by the Responsible Treating Investigator(Up to 12 months of treatment)
- Consumption of Wilate for Prophylactic Treatment(Up to 12 months of treatment)
- Consumption of Wilate for the Treatment of BEs (On-demand Treatment)(Up to 12 months of treatment)
- Consumption of Wilate During Surgical Prophylaxis(Up to 12 months of treatment)
- Number of Participants With Detectable Inhibitory Antibodies Against VWF and/or FVIII(Up to 12 months of treatment)
- Number of Participants With Detectable Thromboembolic Events(Up to 12 months of treatment)
- Change in Haemophilia Joint Health Score(At baseline and at 12 months of treatment)