Prospective, open-label, uncontrolled, phase III study to assess the efficacy, safety, and pharmacokinetics 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
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- The primary endpoint is the overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient.
研究概览
简要总结
This Study is a Prospective, open-label, uncontrolled, phase III study to assess the efficacy, safety, and pharmacokinetics of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in paediatric subjects with congenital fibrinogen deficiency that will be conducted in Three Centres of India.
Primary Endpoint
The primary endpoint is the overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient. The first bleeding episode covers the time period from the 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.
Secondary Endpoints:
• MCF assessment before first infusion and 1 hour after end of first infusion of each documented bleeding episode.
• Fibrinogen plasma level before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion or end of the observation period of each documented bleeding episode).
• Response after the first infusion of each bleeding episode as indicated by incremental IVR, calculated as the maximum increase in plasma fibrinogen (Clauss data) between the pre-infusion and the 3-hour post-infusion measurement, divided by the exact dose of Octafibrin (expressed as mg/kg dosed).
• Efficacy of Octafibrin in all bleeding episodes collected in the study using the investiga-tor’s overall clinical assessment of haemostatic efficacy for bleeding based on a 4-point haemostatic efficacy scale.
• Efficacy of Octafibrin in surgical prophylaxis will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using the following scales:
An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC. The surgical observation periodstarts with the first dose of Octafibrin administered prior to elective surgery (Day 1) and, depending on the severity of the event, will last at least 3 post-operative days for minor and 7 post-operative days for major surgeries or until the day of the last post-operative infusion, whichever comes last.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 0.00 Day(s) 至 12.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Aged <12 years (at the start of treatment).
- •This will include two subgroups of subjects aged between 0 and <6 years and between 6 and <12 years of either gender.
- •2.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.
- •âˆ’ Historical plasma fibrinogen activity of <50 mg/dL or levels below the limit of detection of the local assay method.
- •3.Expected to have an acute bleeding episode (spontaneous or after trauma) or plan-ning to undergo elective surgery.
- •4.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 sur-gery.
- •âˆ’ 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.
- •Presence or history of: − Hypersensitivity to study medication.
- •âˆ’ Deep vein thrombosis or pulmonary embolism within 1 year prior to start of treatment for the bleeding episode or surgery.
- •âˆ’ Arterial thrombosis within 1 year prior to start of treatment for the bleeding episode or surgery − Hypersensitivity to human plasma proteins.
- •âˆ’ Oesophageal varicose bleeding.
- •âˆ’ 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
The primary endpoint is the overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient.
时间窗: The first bleed-ing episode covers the time period from the first Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion
次要结局
- Fibrinogen plasma level before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy(Before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy.)
- MCF assessment before first infusion and 1 hour after end of first infusion of each documented bleeding episode.(Before first infusion and 1 hour after end of first infusion of each documented bleeding episode.)
- Response after the first infusion of each bleeding episode as indicated by incremental IVR, calculated as the maximum increase in plasma fibrinogen between the pre-infusion and the 3-hour post-infusion.(Between the pre-infusion and the 3-hour post-infusion.)
- Efficacy of Octafibrin in all bleeding episodes & surgical prophylaxis(Clinical assessment of haemostatic efficacy for bleeding based on a 4-point haemostatic efficacy scale.)