An Exploratory Study to Evaluate the Dose Response-Relationship of Pharmacodynamic Parameters of AryoSeven, in Patients With Hemophilia With Inhibitors
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Lag time of the thrombin generation curve
研究概览
简要总结
Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.
详细描述
Randomized, double-blind, single dose, 5 ways crossover, clinical trial evaluating four different doses (10 µg/kg, 30 µg/kg, 90 µg/kg, and 270 µg/kg) of AryoSeven (recombinant human FVII activated or eptacog alfa, activated) and one dose of NovoSeven (30 µg/kg) on selected pharmacodynamic parameters (PD) [Primary: Thrombin Generation Assay (TGA)] in male adult and adolescent (>12 years) patients with hemophilia A or B, with an inhibitors titer >5 Bethesda Units [BU] and not in bleeding status. This will be an exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer >5 Bethesda Units [BU]
- •with > 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode
- •Male adults and adolescents (>12 years)
- •Patient informed consent has been obtained [Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent].
- •Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).
排除标准
- •Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
- •Antibodies against Factor VII
- •Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial
- •Platelet count less than 100.000 platelets/mcL (at screening visit)
- •Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism
- •HIV positive with current CD4+ count of less than 200/µL
- •Liver cirrhosis
- •Factor VIII/IX immune tolerance induction regimen planned to occur during the trial
- •Known hypersensitivity to the study medication
- •Parallel participation in another experimental drug trial.
- •Parallel participation in another marketed drug trial that may affect the primary end-point of the study.
- •Concomitant diseases and/or medications, or any other conditions, that render the patient unsuitable for inclusion into the study in the judgement of the investigator.
结局指标
主要结局
Lag time of the thrombin generation curve
时间窗: Up to 30 hours after AryoSeven and NovoSeven injection
Time to 16.7% of peak plasmatic concentration, in minutes.
次要结局
- D-dimer (PD parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- Cmax (PK parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- Time of Cmax (PK parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- Peak height (PD parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- AUCinf (PK parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- F1.2 prothrombin fragments (PD parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- Endogenous Thrombin Potential (PD parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)
- Time to Peak (PD parameter)(Up to 30 hours after AryoSeven and NovoSeven injection)