Monitoring of Anti-TFPI in Hemophilia EUREKA
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Development of a Laboratory Assay to Assess Hemostatic Efficacy of Anti-TFPI Antibodies
研究概览
简要总结
During the development of anti-TFPI antibodies, thrombin generation assay (TGA) was employed using both in vitro measurements (antibodies added to blood samples) and ex vivo approaches (blood samples from patients in phase II and III trials). While a significant improvement in thrombin generation was observed in all samples from patients with severe hemophilia, no correlation with clinical outcomes could be established. Notably, thrombin peak levels were consistently improved even in patients who experienced bleeding episodes. These measurements were conducted in platelet-poor plasma (PPP) with standard reagents, which may not adequately reflect the hemostatic efficacy of anti-TFPI antibodies given their mechanism of action. It is hypothesized that optimizing reagents and utilizing more appropriate biological materials could enhance TGA sensitivity, as previously demonstrated for monitoring emicizumab.
The absence of a laboratory assay to monitor anti-TFPI (tissue factor pathway inhibitor) antibodies poses a significant challenge for managing patients in surgical settings and treating acute severe bleeding. This study aims to develop a reliable assay to evaluate the hemostatic efficacy of anti-TFPI antibodies and their combined procoagulant effect with factor concentrates (FVIII or FIX) or bypassing agents.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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
- •Inclusion Criteria :
- •- Male Patient
- •18 years old
- •severe hemophilia patients A or B (FVIII < 1%,FIX<=2%)
- •on prophylaxis with FVIII or IX concentrates after an adequate washout period of 48h for SHL FVIII molecules, at least 4 days for EHL-FVIII Fc and at least 10 days for EHL-FIX molecules.
- •On prophylaxis with Marstacimab
- •Willing to participate
- •Capable of following protocol procedures under investigator appreciation
排除标准
- •- patients refusing to provide 4 additional blood tubes for research
- •Patient with an other coagulation disorder
- •patients who received an injection of FVIII or FIX during the required washout period
研究组 & 干预措施
Severe adult haemophilia A or B patient with factor levels ≤2%
- 6 on prophylaxis with FVIII or FIX concentrates after an adequate washout period of 48h for SHL FVIII molecules, at least 4 days for EHL-FVIII Fc and at least 10 days for EHL-FIX molecules
- 5 receiving prophylaxis with marstacimab.
干预措施: blood sampling (Biological)
结局指标
主要结局
Development of a Laboratory Assay to Assess Hemostatic Efficacy of Anti-TFPI Antibodies
时间窗: At time of sample analysis (single visit; Day 0)
Assessment of the thrombin generation assay's ability to evaluate the procoagulant effect of anti-TFPI antibodies alone and in combination with factor concentrates (FVIII or FIX) or bypassing agents (rFVIIa, aPCC).
次要结局
- Analytical Sensitivity of TGA to Anti-TFPI Antibodies(Day 0)
- Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect(Day 0)
- Correlation Between TGA Parameters and Clinical Use of Anti-TFPI Therapies(Day 0)
- Detection of Hypercoagulability from Combined Therapy in TGA(Day 0)