Prospective, Open-label, Uncontrolled, Phase III Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery in Paediatric Subjects With Congenital Fibrinogen Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 15
- 试验地点
- 6
- 主要终点
- Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale
研究概览
简要总结
This study will assess the efficacy of Octafibrin, a fibrinogen concentrate in in the on-demand treatment of spontaneous or traumatic bleeding episodes in paediatric patients less than 12 years of age.The planned study duration is up to 5 years. The study will be considered completed when a minimum of 6 subjects (i.e., at least 3 subjects aged between 0 and <6 years and 3 subjects aged between 6 and <12 years) have at least one documented bleeding episode and when in total a minimum of 2 surgical procedures have been performed.
All patients will undergo a pharmacokinetic (PK) study after screening. This will have a duration of 14 days, after which a patient can be treated for a bleeding episode or planned surgical procedure when they occur.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged <12 years (at the start of treatment).
- •Documented diagnosis of congenital fibrinogen deficiency, expected to require on-demand treatment for bleeding or surgical prophylaxis:
- •Fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrino-genaemia.
- •Historical plasma fibrinogen activity of <50 mg/dL or levels below the limit of detection of the local assay method.
- •Expected to have an acute bleeding episode (spontaneous or after trauma) or planning to undergo elective surgery.
- •Informed consent signed by the subject's legal guardian.
排除标准
- •Life expectancy <6 months.
- •Bleeding disorder other than congenital fibrinogen deficiency, including dysfi-brinogenaemia.
- •Prophylactic treatment with a fibrinogen concentrate.
- •Treatment with:
- •Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks prior to start of treatment for the PK phase, a bleeding episode, or surgery.
- •Any coagulation-active drug (i.e., non-steroidal anti-inflammatory drugs, war-farin, coumarin derivatives, platelet aggregation inhibitors) within 1 week prior to start of the PK phase or treatment for the bleeding episode or surgery, or as a planned or expected medication during the time period from Day 1 until 24 hours (i.e., 1 day) after the last Octafibrin infusion.
- •Presence or history of:
- •Hypersensitivity to study medication.
- •Deep vein thrombosis or pulmonary embolism within 1 year prior to start of treatment for the bleeding episode or surgery.
- •Arterial thrombosis within 1 year prior to start of treatment for the bleeding episode or surgery
- •Hypersensitivity to human plasma proteins.
- •Oesophageal varicose bleeding.
- •End-stage liver disease (i.e., Child-Pugh score B or C).
- •Known positive HIV infection with a viral load >200 particles/μL or >400,000 copies/mL.
- •Polytrauma 1 year prior to start of treatment for the bleeding episode or surgery.
- •Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or any time in the past.
- •Acute or chronic medical condition which may, in the opinion of investigator, affect the conduct of the study, including subjects receiving immune-modulating drugs (other than anti-retroviral chemotherapy), such as alpha-interferon, predni-sone (equivalent to >10 mg/day), or similar drugs, at study start.
- •Treatment with IMP in another interventional clinical study currently or during the past 4 weeks.
结局指标
主要结局
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale
时间窗: First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last
The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4-point haemostatic efficacy scale (excellent, good, moderate or none). Excellent result was defined as immediate cessation of bleeding; 'Good' was eventual complete cessation of bleeding; 'Moderate' was incomplete cessation of bleeding and 'None' was no cessation of bleeding with alternative haemostatic intervention required. The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 2-point Haemostatic Efficacy Scale
时间窗: From the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last.
The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 2-point haemostatic efficacy scale (success and failure). Efficacy rating of excellent or good on the four-point scale (above) indicated success and efficacy rating of moderate or none indicated failure. The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.
次要结局
- Efficacy of Octafibrin in All Bleeding Episodes Based on a Two-point Haemostatic Efficacy Scale(First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last)
- Single-dose Pharmacokinetics of Octafibrin: Terminal Elimination Half-life (t1/2)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Volume of Distribution (Vss)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Area Under the Concentration-time Curve Normalised (AUCnorm)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Maximum Plasma Concentration (Cmax)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Mean Residence Time (MRT)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Time to Reach Maximum Plasma Concentration (Tmax)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Single-dose Pharmacokinetics of Octafibrin: Clearance (Cl)(Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion)
- Incremental in Vivo Recovery Following the First Infusion of Octafibrin Administration for the Treatment of the First Bleeding Episode and of All Bleeding Episodes(Pre-infusion and 3 hours post-infusion)
- Efficacy of Octafibrin in Surgical Prophylaxis Based on a Two-point Haemostatic Efficacy Scale(First dose of Octafibrin prior to surgery until last day of post-operative infusion)
- Safety Assessment: Immunogenicity Testing for Anti-fibrinogen Antibodies(Start of the first Octafibrin infusion to the end of each 30-day observation and follow-up period for on-demand treatment)
- Single-dose Pharmacokinetics of Octafibrin: Response - Incremental in Vivo Recovery (IVR)(Between the pre-infusion and the 3-hour post-infusion)
- Change in Maximum Clot Firmness (MCF) for the First Bleeding Episode for Each Patients and for All Bleeding Episodes(Before first infusion and 1 hour post-infusion of Octafibrin)
- Change in the Fibrinogen Level for All Bleeding Episodes up to 1 Hour-post Infusion for the First Bleeding Episode and All Bleeding Episodes(Pre-infusion and 1 hour post-infusion of Octafibrin)
- Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale(First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last)
- Patients With Elevated Values of Prothrombin Fragments 1+2(3 hours post-infusion of Octafibrin)
- Safety Assessment: Adverse Events(Start of the first Octafibrin infusion to the end of PK, end of 30-day observation and follow-up period for on-demand treatment, or the end of the surgical observation period)
- Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale(First dose of Octafibrin prior to surgery until last day of post-operative infusion)