Randomized, Multicenter, Single-dose, Cross-over, Double-blind Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Maximum plasma concentration of the factor VII activity (Cmax).
研究概览
简要总结
The purpose of this multicentre, randomized, double blinded, single dose, two-way cross-over study, is to compare the pharmacokinetics (PK) of biosimilar eptacog alfa (activated) with Novoseven in 24 patients, adult and children (>12 years), not bleeding, with inherited coagulation factor VII (FVII) deficiency (FVII <1%). Patients will be randomized to receive either a single dose of eptacog alfa biosimilar 30 μg/kg and one single dose of NovoSeven 30 μg/kg, or vice versa, with doses separated by a washout period. All patients will be followed 12 months and will receive biosimilar eptacog alfa, on demand, for every bleeding episode that should occur - or - for prophylaxis, with the aim of monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Blinding is performed by an independent third party operator (nurse/pharmacist, unblinded), who will prepare undistinguishable syringes with patient's dosing and labeling. Central lab operators will be blinded.
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a confirmed diagnosis of congenital, severe Factor VII deficiency (FVII <1%), with > 2 episodes of bleeding/year requiring treatment with FVII infusions, in non bleeding status.
- •Patients for the Additional group for immunogenicity should be enrolled when in a bleeding episode requiring treatment with FVII.
- •Male and female subjects
- •Adult and children (>12 years)
- •Written informed consent. For minor patients, parent/legal guardian will provide consent and, when possible, patient assent will also be obtained. For compromised patients their designated proxy must provide informed consent.
排除标准
- •Any other type of congenital or acquired coagulopathy (except congenital Factor VII deficiency), such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
- •Antibodies against Factor VII
- •Patients entering the PK Study Group who have not suspended prophylactic regimen with Novoseven or AryoSeven (biosimilar eptacog alfa) 3 days before starting the trial (receiving first dose of study medication).
- •Patients entering the Additional Group for Immunogenicity study, only, who have been exposed to AryoSeven before starting study [patients who have received Novoseven (on demand or in prophylaxis) before starting study are allowed]
- •Platelet count less than 100.000 platelets/μl (at screening visit)
- •Patients who have received routine (prophylactic) treatment with rFVIIa in the period between screening visit (visit 1) and visit 2 of this study (first dose administration)
- •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
- •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.
结局指标
主要结局
Maximum plasma concentration of the factor VII activity (Cmax).
时间窗: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
Measurement of plasma level of factor VII clotting activity (FVII:C) \[one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)\],
Area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast)
时间窗: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
Measurement of plasma level of factor VII clotting activity (FVII:C) \[one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)\],
次要结局
- Clinical response in controlling acute bleeding.(2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar))
- Time of Cmax (tmax)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- First order rate constant associated with the terminal (log-linear) portion of the curve (λz)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Clearance (CL)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Elimination half-life (t½)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Mean residence time (MRT)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Area under the plasma concentration-time curve from time 0 to infinity (AUCinf)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Fraction of the total AUCinf that was derived by extrapolation beyond tlast (AUCextra)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Volume of distribution (Vss)(Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase)
- Immunogenicity(On plasma samples obtained at screening visit, before the second dose/second drug administration, and then every 3 months for a year.)
- Adverse Events(Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.)