NCT03879135已完成3 期
A Phase 3b, Prospective, Open-Label, Uncontrolled, Multicenter Study on Long-Term Safety and Efficacy of rVWF in Pediatric and Adult Subjects With Severe Von Willebrand Disease (VWD)
Baxalta now part of Shire31 个研究点 分布在 9 个国家目标入组 38 人开始时间: 2019年4月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 31
- 主要终点
- Spontaneous Annualized Bleeding Rate (sABR)
研究概览
简要总结
The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not related to trauma) bleeding episodes in pediatric and adult participants during the first 12 months on study treatment.
The participants will be treated with rVWF for a maximum of 3 years. Their von Willebrand Disease will be treated according to Investigational product (IP) dosing directions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant will not be considered eligible for the study without meeting all of the criteria below.
- •Participants who have completed Study 071301 or Study 071102 (or participants who have completed the surgery arm treatment in Study 071102 and want to continue to receive on-demand (OD) treatment) and are willing to immediately transition into this study, must meet the following 2 criteria to be eligible for this study:
- •If female of childbearing potential, has a negative blood/urine pregnancy test at screening and agrees to employ highly effective birth control measures for the duration of the study.
- •Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
- •New participants (Cohort 4) who meet the above 2 and ALL the following additional criteria are eligible for this study:
- •- Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline von Willebrand factor: Ristocetin cofactor (VWF:RCo) <20 International Units per deciliter [IU/dL]) with a history of requiring substitution therapy with von Willebrand factor (vWF) concentrate to control bleeding:
- •Type 1 (VWF:RCo <20 IU/dL) or,
- •Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,
- •Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to (<=) 3 IU/dL).
- •Diagnosis is confirmed by genetic testing and multimer analysis, documented in participant history or at screening.
- •Participant has been receiving OD therapy with VWF products for at least 12 months, and prophylactic treatment is recommended by the investigator.
- •Participant has greater than or equal to (>=) 3 documented spontaneous bleeds (not including menorrhagia) requiring VWF treatment during the past 12 months.
- •Participant has available records that reliably evaluate type, frequency, and treatment of bleeding episodes for at least 12 months preceding enrollment; up to 24 months of retrospective data should be collected if available.
- •Participant is >=12 years old at the time of screening and has a body mass index >=15 but <40 kilogram per meter square (kg/m^2).
排除标准
- •The participant will be excluded from the study if any of the following exclusion criteria are met.
- •The participant has been diagnosed with Type 2N VWD, pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg, qualitative and quantitative platelet disorders or elevated prothrombin time (PT)/international normalized ratio [INR] >1.4).
- •The participant has a history or presence of a VWF inhibitor at screening.
- •The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer >=0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or >=0.6 BU (by Bethesda assay).
- •The participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
- •The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or animal allergies.
- •The participant has a medical history of a thromboembolic event.
- •The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count <200/cubic millimeters (mm^3).
- •The participant has been diagnosed with significant liver disease per investigator's medical assessment of the participant's current condition or medical history or as evidenced by, but not limited to any of the following: serum alanine aminotransferase (ALT) greater than 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-Pugh class B or C.
- •The participant has been diagnosed with renal disease, with a serum creatinine (CR) level >=2.5 milligrams per deciliter (mg/dL).
- •The participant has a platelet count <100,000/milliliter (mL) at screening.
- •The participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent (or assent, if appropriate).
- •The participant is pregnant or lactating at the time of enrollment.
- •The participant has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
- •The participant has participated in another clinical study involving another investigational product (IP) 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.
- •The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
- •For new OD participants, the participant is scheduled for a surgical intervention.
- •The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- •The participant has 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.
- •The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.
- •Delay criteria Only for Cohort 4, if the participant presents with an acute bleeding episodes or acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, and non-seasonal asthma) the screening visit will be postponed until the participant has recovered. For all other participants, end of study (EOS) visit for 071102 or 071301 will be completed per protocol and the completed EOS in Study 071102 or 071301 will also serve as the screening visit for this continuation study (SHP677-304).
研究组 & 干预措施
On-Demand
Experimental
Participants will receive recombinant von Willebrand factor (rVWF) (with or without ADVATE).
干预措施: rVWF (Biological)
On-Demand
Experimental
Participants will receive recombinant von Willebrand factor (rVWF) (with or without ADVATE).
干预措施: rFVIII (Biological)
Prophylaxis
Experimental
Participants will receive recombinant von Willebrand factor (rVWF).
干预措施: rVWF (Biological)
Prophylaxis
Experimental
Participants will receive recombinant von Willebrand factor (rVWF).
干预措施: rFVIII (Biological)
结局指标
主要结局
Spontaneous Annualized Bleeding Rate (sABR)
时间窗: Up to 12 months
sABR was derived as \[number of treated bleeds\] / \[duration in years\]. Bleeds with unknown causality were considered as spontaneous. Bleeds were categorized based on the investigator assessment of cause. sABR during the first 12 months of prophylactic treatment with rVWF (vonicog alfa) was reported.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Up to 5.8 years)
- Number of Participants Based on Severity of TEAEs(Up to 5.8 years)
- Number of Participants Based on Causality of TEAEs(Up to 5.8 years)
- Number of Participants With Thromboembolic Events(Up to 5.8 years)
- Number of Participants With Hypersensitivity Reactions(Up to 5.8 years)
- Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (VWF)(Up to 5.8 years)
- Number of Participants Who Developed Neutralizing Antibodies to Factor VIII (FVIII)(Up to 5.8 years)
- Number of Participants Who Developed Total Binding Antibodies to Von Willebrand Factor (VWF)(Up to 5.8 years)
- Number of Participants Who Developed Total Binding Antibodies to Factor VIII (FVIII)(Up to 5.8 years)
- Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins(Up to 5.8 years)
- Number of Participants Who Developed Binding Antibodies to Mouse Immunoglobulin G (IgG)(Up to 5.8 years)
- Number of Participants Who Develop Binding Antibodies to Recombinant Furin (rFurin)(Up to 5.8 years)
- Number of Participants With Clinically Significant Changes in Vital Signs(Up to 5.8 years)
- Number of Participants With Clinically Significant Changes in Laboratory Parameters(Up to 5.8 years)
- Spontaneous Annualized Bleeding Rate (sABR) Under Prophylactic Treatment(Up to 5.8 years)
- Number of Participants Categorized Based on Weekly Number of Infusions(Up to 5.8 years)
- Number of Participants Categorized Based on Spontaneous Annualized Bleeding Rate (sABR)(Up to 5.8 years)
- Time to First Bleeding Event on Prophylaxis Treatment(Up to 5.8 years)
- Spontaneous Annualized Bleeding Rate (sABR) by Location of Bleeding(Up to 5.8 years)
- Total Number of Infusions During Prophylactic Treatment(Up to 5.8 years)
- Average Number of Infusions Per Week During Prophylactic Treatment(Up to 5.8 years)
- Total Weight Adjusted Consumption of Recombinant Von Willebrand Factor (rVWF) (Vonicog Alfa) Per Participant During Prophylactic Treatment(Up to 5.8 years)
- Number of Participants Who Achieved Transfusion-free Maintenance of Hemoglobin Levels(Up to 5.8 years)
- Change From Baseline in Ferritin Levels Over Time(Up to 5.8 years)
- Overall Hemostatic Efficacy Rating(Initial 12 months of study)
- Number of Infusions of Vonicog Alfa(Up to 5.8 years)
- Number of Infusions of ADVATE(Up to 5.8 years)
- Weight-adjusted Consumption of Vonicog Alfa Per Bleeding Episode(Up to 5.8 years)
- Weight-adjusted Consumption of ADVATE Per Bleeding Episode(Up to 5.8 years)
研究者
研究点 (31)
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