Evaluation of the Pharmacokinetic Profile, Clinical Efficacy and Safety of the Von Willebrand Factor Contained in FANHDI® (Double-inactivated Human Anti-hemophilic Factor) in Pediatric Subjects With Severe Von Willebrand Disease
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 8
- 试验地点
- 8
- 主要终点
- AUC^0-inf of coagulation factor VIII activity (FVIII:C)
研究概览
简要总结
Multicenter, prospective, non-controlled study in a pediatric cohort (<6 years-old) with severe (type 2 or 3) hereditary Von Willebrand Disease (VWD).
详细描述
This is a multicenter, prospective, open-label, and single-arm study. The study population is planned to include 8 pediatric subjects (<6 years of age) with severe (type 2 or 3) hereditary VWD without inhibitors and with no active bleeding at the time of inclusion. Eligible subjects will receive a single dose of Fanhdi for a PK evaluation and will be followed for 12 months for which the efficacy and safety of Fanhdi will be assessed. In addition, the type 3 VWD subjects, after 6 months of follow-up of the first infusion, will receive the second dose as in the 1st PK evaluation and undergo a 2nd PK evaluation.
The study will consist of 2 phases:
- PK profile evaluation in which all eligible subjects will receive a single dose of 80 IU/kg von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) of Fanhdi. In addition, after 6 months of follow-up of the first infusion, type 3 VWD subjects will receive the second dose of Fanhdi and undergo a 2nd PK evaluation with a reduced sampling schedule.
- A 12-month Follow-up period during which the safety and efficacy of Fanhdi will be assessed in the prevention and management of bleeding episodes and/or management of perioperative hemostasis during surgery and/or invasive procedures.
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
- 2 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects diagnosed with severe (type 2 or 3) hereditary VWD (VWF:RCo<15-20 IU/dL), or VWF:Act<15-20 IU/dL.
- •Subjects under 6 years of age.
- •Signed informed consent form (ICF) provided by an authorized representative on behalf of the subject in accordance with local law and institutional policy.
排除标准
- •Subjects diagnosed with acquired VWD.
- •Subjects with active bleeding at the time of the first infusion or within 10 days prior to the infusion.
- •Subjects who have been treated with DDAVP or another FVIII containing VWF concentrate during the 5 days prior to the infusion of the Fanhdi. This treatment-free period may be reduced to 3 days for subjects with type 3 VWD.
- •Subject who are positive for anti-VWF or anti-FVIII antibodies (≥0.5 Bethesda Units) or has been positive in the history of their disease.
- •Subjects with a known allergies/intolerance to any substance contained in Fanhdi.
- •Subjects with a known history of anaphylactic reaction(s) to blood or blood components.
- •Subjects presenting severe platelet activity dysfunction due to the use of drugs (aspirin, other nonsteroidal anti-inflammatory drugs [NSAIDs], etc.) or a congenital or acquired platelet function disorder or other concomitant processes that may interfere with coagulation.
- •Subjects have a known previous infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV), or have clinical signs and symptoms consistent with current HAV, HBV, HCV or HIV infection.
- •Subjects presenting anemia (hemoglobin <11 g/dL).
- •Subjects diagnosed with metabolic diseases that are not clinically controlled, such as diabetes mellitus, which could potentially interfere with the interpretations of the study.
- •Participated in another clinical trial within 30 days prior to the screening visit or has received any investigational product (IP) within 3 months prior to the screening visit.
- •If it is anticipated that the subject will be treated with other products containing FVIII or VWF different from Fanhdi throughout the subject's participation.
- •Subjects who, in the opinion of the investigator, may have compliance problems with the protocol.
研究组 & 干预措施
plasma-derived FVIII/VWF concentrate
Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)
干预措施: plasma-derived FVIII/VWF concentrate (Drug)
结局指标
主要结局
AUC^0-inf of coagulation factor VIII activity (FVIII:C)
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C
in vivo recovery of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Clearance of FVIII:C
时间窗: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Total plasma and/or serum clearance
AUC^0-inf of von Willebrand factor antigen (VWF:Ag)
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag
AUC^0-T of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:Ag
AUC^0-T of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:CB
in vivo recovery of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
in vivo recovery of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
C^max of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Maximum observed plasma and/or serum concentration of VWF:Ag
Elimination rate constant of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
C^max of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
Maximum observed plasma and/or serum concentration of VWF:RCo
C^max of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Maximum observed plasma and/or serum concentration of VWF:CB
T^max of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
Time of maximum observed plasma and/or serum concentration of VWF:RCo
Clearance of VWF:Ag
时间窗: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Total plasma and/or serum clearance
Elimination rate constant of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo)
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve extrapolated to infinity of VWF:RCo
AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB)
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve extrapolated to infinity of VWF:CB
AUC^0-T of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of FVIII:C
in vivo recovery of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Half-life of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Terminal elimination half-life
AUC^0-T of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:RCo
Half-life of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Terminal elimination half-life
Half-life of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
Terminal elimination half-life
C^max of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Maximum observed plasma and/or serum concentration of FVIII:C
Mean residence time of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Average amount of time that a single molecule of drug stays in the body.
Clearance of VWF:RCo
时间窗: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Total plasma and/or serum clearance
Elimination rate constant of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Volume of distribution of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
T^max of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Time of maximum observed plasma and/or serum concentration of FVIII:C
T^max of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Time of maximum observed plasma and/or serum concentration of VWF:Ag
T^max of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Time of maximum observed plasma and/or serum concentration of VWF:CB
Mean residence time of VWF:RCo
时间窗: Prior to the first infusion up to 72 hours postinfusion
Average amount of time that a single molecule of drug stays in the body of VWF:RCo
Mean residence time of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Average amount of time that a single molecule of drug stays in the body of VWF:Ag
Mean residence time of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
Average amount of time that a single molecule of drug stays in the body of VWF:CB
Clearance of VWF:CB
时间窗: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Total plasma and/or serum clearance
Elimination rate constant of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Volume of distribution of VWF:Ag
时间窗: Prior to the first infusion up to 72 hours postinfusion
Volume of distribution of FVIII:C
时间窗: Prior to the first infusion up to 72 hours postinfusion
Volume of distribution of VWF:CB
时间窗: Prior to the first infusion up to 72 hours postinfusion
VWF multimeric pattern
时间窗: Prior to the first infusion up to 12 hours postinfusion
For type 3 VWD subjects
次要结局
未报告次要终点