CTRI/2012/01/002390Other3 期
A Phase 3 Clinical Study to Determine the Pharmacokinetics, Safety and Efficacy of rVWF:rFVIII and rVWF in the Treatment of Bleeding Episodes in Subjects Diagnosed with Von Willebrand Disease
试验速览
- 阶段
- 3 期
- 状态
- Other
- 入组人数
- 45
- 试验地点
- 3
- 主要终点
- Number of subjects with a treatment success for treated bleeding episodes.
研究概览
简要总结
This is a Phase 3,multi-center, open-label study to evaluate Pharmacokinetics, safety andeffectiveness in the treatment of bleeding episodes in patients with severetype 3 VWD, non-type 3 WVD and type 2N VWD disease. The study will be dividedin 2 parts (A&B). Approximately 45 patients will be enrolled. The primaryendpoint is a pharmacokinetic measurement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •â€¢The subject has been diagnosed with: o type 3 VWD (VWF:Ag ≤3 IU/dl) or o severe non-type 3 VWD (VWF:RCo <20 IU/dL) or o type 2N VWD (FVIII:C <10% and historically documented genetics) •The subject, who participates for the treatment for bleeding episodes, has had a minimum of 6 documented bleeds (medical history) requiring VWF coagulation factor replacement therapy during the previous3 years prior to enrollment.
- •â€¢The subject has a Karnofsky score ≥
- •â€¢If female of childbearing potential, subject presents with a negative pregnancy test •The subject agrees to employ adequate birth control measures for the duration of the study.
- •â€¢Subject is willing and able to comply with the requirements of the protocol.
排除标准
- •â€¢The subject has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or elevated PT/international normalized ratio [INR] >1.4).
- •â€¢The subject has a documented history of a VWF:RCo half-life of <6 hours.
- •â€¢The subject has a history or presence of a VWF inhibitor at screening.
- •â€¢The subject has a history or presence of a factor VIII (FVIII) inhibitor with a titer ≥0.4 BU (by Nijmegen assay) or ≥0.6 BU (by Bethesda assay).
- •â€¢The subject has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.
- •â€¢The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
- •â€¢The subject has a medical history of a thromboembolic event.
- •â€¢The subject is HIV positive with an absolute CD4 count <200/mm
- •â€¢The subject has been diagnosed with cardiovascular disease (New York Heart Association [NYHA] classes 1-4) •The subject has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, non-seasonal asthma) at screening.
- •â€¢The subject has been diagnosed with significant liver disease as evidenced by 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).
- •â€¢The subject has been diagnosed with renal disease, with a serum creatinine level ≥2 mg/dL.
- •â€¢In the judgment of the investigator, the subject has another clinically significant concomitant disease (eg, uncontrolled hypertension) that may pose additional risks for the subject.
- •â€¢The subject has been treated with an imunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent.
- •â€¢Subject is pregnant or lactating at the time of enrollment.
- •â€¢Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study.
- •â€¢The subject has a history of drug or alcohol abuse within the 2 years prior to enrollment.
- •â€¢The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- •â€¢The subject 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.
- •â€¢The subject is in prison or compulsory detention by regulatory and/or juridical order.
结局指标
主要结局
Number of subjects with a treatment success for treated bleeding episodes.
时间窗: 12 month
次要结局
- Number of treated bleeding episodes with an efficacy rating of excellent or good(12 month)
- Number of infusions and rVWF:rFVIII and/or rVWF units per bleeding episode(12 month)
- Development of inhibitory and total binding anti-VWF antibodies(12 month)
- Development of inhibitory antibodies to FVIII, Time-points(12 month)
- Development of antibodies to Chinese hamster ovary (CHO) proteins, mouse immunoglobulin G (IgG) and rFurin(12 month)
- Occurrence of thrombotic events, Time-points(12 month)
- Other IP related AEs, such as clinically significant changes in routine laboratory parameters (hematology and clinical chemistry) and vital signs(12 month)
- Area under the plasma concentration/time curve from time 0 to infinity (AUC0-∞/Dose); area under the plasma concentration/time curve from time 0 to 96 hours (AUC0-96h/Dose); mean residence time (MRT); clearance (CL); incremental recovery (IR), elimination phase half-life (T1/2); volume of distribution at steady state (Vss) of VWF Ristocetin cofactor (VWF:RCo), VWF antigen (VWF:Ag), VWF collagen-binding (VWF:CB), and FVIII(6 month)
- In vivo recovery (IVR) of VWF:RCo, VWF:Ag and VWF:CB(12 month)
- Comparison of intra-subject PK of VWF:RCo, VWF:CB and VWF:Ag at baseline and after 6 months in a subset of at least 20 subjects with severe VWD (minimum 6 subjects with type 3 VWD)(6 month)
研究者
研究点 (3)
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