A Prospective, Controlled, Randomised, Crossover Study Investigating the Pharmacokinetic Properties, Surrogate Efficacy and Safety of Octafibrin Compared to Haemocomplettan® P/RiaSTAPTM in Patients With Congenital Fibrinogen Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 22
- 试验地点
- 12
- 主要终点
- Ratio of Octafibrin/FIBRYGA® to Haemocomplettan® P/RiaSTAP(TM) for Fibrinogen Activity Normalized Area Under the Curve Unstandardized
研究概览
简要总结
The purpose of this study is to investigate pharmacokinetic properties, surrogate efficacy and safety of Octafibrin compared to Haemocomplettan® P/RiaSTAPTM in patients with congenital fibrinogen deficiency
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 12 years.
- •Documented congenital fibrinogen deficiency (afibrinogenemia).
排除标准
- •Life expectancy > 6 month.
- •Bleeding disorder other than congenital fibrinogen deficiency.
- •Presence or history of hypersensitivity to study medication.
- •Presence or history of deep vein thrombosis or pulmonary embolism within 1 year prior to enrollment.
- •Presence or history of arterial thrombosis with 1 year prior to enrollment.
- •Hypersensitivity to human plasma products.
- •Acute bleeding.
- •Pregnant or currently breast-feeding women.
- •Suspicion of an anti-fibrinogen inhibitor as indicated by previous in vivo recovery (if available).
- •Blood or plasma donation in the 3 months prior to enrollment.
- •Human immunodeficiency virus (HIV) positive with a viral load > 200 particles/µl or > 400000 copies/mL.
- •End-stage liver disease.
- •History of oesophageal varicose bleeding.
研究组 & 干预措施
Octafibrin followed by Haemocomplettan® P or RiaSTAPTM
Participants received Octafibrin 70 mg/kg intravenously once followed by Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once 45 days later.
干预措施: Octafibrin (Biological)
Octafibrin followed by Haemocomplettan® P or RiaSTAPTM
Participants received Octafibrin 70 mg/kg intravenously once followed by Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once 45 days later.
干预措施: Haemocomplettan® P or RiaSTAPTM (Biological)
Haemocomplettan® P or RiaSTAPTM followed by Octafibrin
Participants received Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once followed by Octafibrin 70 mg/kg intravenously once 45 days later.
干预措施: Octafibrin (Biological)
Haemocomplettan® P or RiaSTAPTM followed by Octafibrin
Participants received Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once followed by Octafibrin 70 mg/kg intravenously once 45 days later.
干预措施: Haemocomplettan® P or RiaSTAPTM (Biological)
结局指标
主要结局
Ratio of Octafibrin/FIBRYGA® to Haemocomplettan® P/RiaSTAP(TM) for Fibrinogen Activity Normalized Area Under the Curve Unstandardized
时间窗: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment
Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The mean ratio of normalized area under the curve was calculated as Octafibrin/FIBRYGA® over Haemocomplettan® P/RiaSTAP(TM)
Comparison of Maximum Clot Firmness Between Octafibrin/FIBRYGA® and Haemocomplettan® P/RiaSTAP(TM) at 1 hr Post Infusion
时间窗: 1 hour post-treatment
Thromboelastometry (ROTEM®) was used to measure maximum clot firmness. Thromboelastometry is a method for the continuous measurement of clot formation. Maximum clot firmness is a functional parameter that depends on the activation of coagulation, the platelet and fibrinogen content of the blood sample, and the polymerisation and cross-linking of the fibrin network. In order to obtain comparable results from all study centres, maximum clot firmness data were assessed from frozen citrated plasma samples in a central laboratory. As these samples did not contain platelets that would be found in the whole blood assay, the fibrinogen content primarily defined the maximum clot firmness.
次要结局
- Fibrinogen Activity Normalized Area Under the Curve Unstandardized(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Fibrinogen Activity Normalized Area Under the Curve Standardized(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Maximum Plasma Concentration Normalized (Cmaxnorm)(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Maximum Plasma Concentration (Cmax) Unstandardized(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Maximum Plasma Concentration (Cmax) Standardized(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Incremental in Vivo Recovery(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Classical in Vivo Recovery(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Time to Reach Maximum Plasma Concentration (Tmax)(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Terminal Half-life (t½)(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Mean Residence Time (MRT)(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Clearance(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)
- Volume of Distribution at Steady State (Vss)(Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment)