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临床试验/NCT02283268
NCT02283268已完成3 期

A Phase 3, Prospective, Multicenter Study to Evaluate Efficacy and Safety of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Elective Surgical Procedures in Subjects With Severe Von Willebrand Disease

Baxalta now part of Shire68 个研究点 分布在 13 个国家目标入组 24 人开始时间: 2015年4月1日最近更新:
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适应症

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
24
试验地点
68
主要终点
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician)
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of the study is to assess the efficacy and safety of recombinant von Willebrand factor (rVWF) with or without ADVATE in major and minor elective surgical procedures in adult patients with hereditary severe von Willebrand disease (VWD).

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
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Diagnosis of severe von Willebrand disease (VWD) as listed below and elective surgical procedure planned
  • •Type 1 (Von Willebrand factor : Ristocetin cofactor activity (VWF:RCo) <20 IU/dL), or
  • •Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2N (FVIII:C<10% and historically documented genetics), Type 2M, or
  • •Type 3 (Von Willebrand factor antigen (VWF:Ag) ≤ 3 IU/dL)
  • •VWD with a history of requiring substitution therapy with von Willebrand factor (VWF) concentrate to control bleeding
  • •If type 3 VWD (VWF Antigen /VWF:Ag ≤ 3 IU/dL), participant has a medical history of at least 20 exposure days to VWF/FVIII coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma)
  • •If type 1 or type 2 VWD, participant has a medical history of 5 exposure days or a past major surgery requiring VWF/FVIII coagulation factor concentrates (including cryoprecipitate or fresh frozen plasma)
  • •Participant is at least 18 years of age
  • •If female of childbearing potential, participant presents with a negative pregnancy test
  • •If applicable, participant agrees to employ adequate birth control measures for the duration of the study
  • •Participant is willing and able to comply with the requirements of the protocol

排除标准

  • •Diagnosis of pseudo VWD or another hereditary or acquired coagulation disorder (eg, qualitative and quantitative platelet disorders or elevated prothrombin time [PT] / international normalized ratio [INR] > 1.4)
  • •History or presence of a VWF inhibitor at screening
  • •History or presence of a factor VIII (FVIII) inhibitor with a titer ≥ 0.4 BU (Nijmegen-modified Bethesda assay ) or ≥ 0.6 BU (by Bethesda assay)
  • •Known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins
  • •Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies
  • •Medical history of a thromboembolic event
  • •HIV positive with an absolute CD4 count < 200/mm3
  • •Platelet count < 100,000/mL
  • •Diagnosis of significant liver disease, as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg. presence of otherwise unexplained splenomegaly, history of esophageal varices) or liver cirrhosis classified as Child B or C
  • •Diagnosis of renal disease, with a serum creatinine level ≥ 2 .5mg/dL
  • •Participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent
  • •Participant is pregnant or lactating at the time informed content is obtained
  • •Participant has participated in another clinical study involving an investigational product (IP), other than rVWF with or without ADVATE, or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. However, eligible patients participating in the rVWF Prophylaxis Study (071301) may be enrolled.
  • •Progressive fatal disease and/or life expectancy of less than 3 months
  • •Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures
  • •Participant suffers from a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude
  • •Participant is in prison or compulsory detention by regulatory and/or juridical order
  • •Participant is a member of the study team conducting this study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees.

结局指标

主要结局

Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician)

时间窗: 24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intra-, and postoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intra-, and postoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intra-, and postoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

次要结局

  • Occurrence of Adverse Events(From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery))
  • Occurrence of Thrombotic Events(From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery))
  • Number of Participants Who Developed Inhibitory and Total Binding Antibodies to Von Willebrand Factor (VWF) and Inhibitory Antibodies to Factor VIII (FVIII)(Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).)
  • Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon(Day 0 (at completion of surgery))
  • Intraoperative Actual Blood Loss Relative to Predicted Blood Loss(Day 0 (at completion of surgery))
  • Daily Intra- and Postoperative Weight-adjusted Dose of rVWF With or Without ADVATE(Daily, from day of surgery through postoperative Day 14 (± 2 days))
  • Occurrence of Severe Allergic Reactions (eg, Anaphylaxis)(From first infusion of investigational product through study completion (ie, 14 (± 2) days post surgery))
  • Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon(Day 0 (at completion of surgery))
  • Pharmacokinetics: Clearance (CL)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Intraoperative Hemostatic Efficacy Score as Assessed by the Operating Surgeon(Day 0 (at completion of surgery))
  • Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion (AUC 0-72 h/Dose)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Pharmacokinetics: Mean Residence Time (MRT)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Pharmacokinetics: Incremental Recovery (IR)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) or Recombinant Furin (rFurin)(Testing occurred throughout the study at screening, prior PK infusion, pre-surgery, post surgery in case of excessive bleeding or unexplained bleeding, at postoperative day 7 and at study completion visit (ie. 14 (± 2) days post surgery).)
  • Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞ /Dose)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Pharmacokinetics: Elimination Phase Half-life (T1/2)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)
  • Pharmacokinetics: Volume of Distribution at Steady State (Vss)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 30 (± 5) minutes, 60 (± 5) minutes, 6 (± 1) hours, 12 (± 1) hours, 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.)

研究者

发起方
Baxalta now part of Shire
申办方类型
Industry
责任方
Sponsor

研究点 (68)

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