A Single Group, Non-Randomized, Multicenter, Interventional Phase-3 Study to Investigate Efficacy, Safety and Pharmacokinetics of Fibrogen- ITM (Human Fibrinogen Injection) for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery in Patients with Congenital Fibrinogen Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- To demonstrate the haemostatic efficacy of
研究概览
简要总结
Pharmacokinetic, Efficacy and Safety Study of Fibrogen-I for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 0.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for the study as described in Appendix 10.1.3 and in this protocol and is willing to participate in the study.
- •Parent(s) (preferably both if available or per local requirements) must sign an ICF indicating that they understand the purpose of, and procedures required for the study and is willing to allow the child to participate in the study.
- •Assent is also required of children capable of understanding the nature of the study as described in Informed Consent Process in Appendix 10.1.
- •Male or female.
- •Age of 0 to 75 (completed years) at the time of signing the informed consent.
- •Documented diagnosis of congenital fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrinogenaemia: Participants with a fibrinogen level undetectable, or equal or less than 50 mg per dL determined by both Clauss and antigen methods at Screening Visit.
- •Expected to require treatment for acute bleeding episode (spontaneous or after trauma [defined as any accidental event leading to acute bleeding]) or prophylaxis of bleeding before a surgical intervention or invasive procedure.
排除标准
- •Known allergies or hypersensitivity to the investigational interventions, human plasma proteins, blood-derived products or components excipients thereof [human albumin, Larginine hydrochloride, sodium citrate, sodium chloride; refer to the prescribing information of Fibrogen-I that, either manifested as severe immediate hypersensitivity reactions, including anaphylaxis prohibiting the further treatment with fibrinogen concentrate or contraindicates participation in the study in the opinion of the investigator.
- •Documented history of immunoglobulin A (IgA) deficiency and antibodies against IgA.
- •Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months before the first dose of investigational intervention.
- •For participants with evidence of chronic hepatitis B virus (HBV) infection who are HBsAg positive but are already established on highly effective viral suppression with HBV DNA below the Level of Quantification at screening, and when the intent is for viral suppression to continue throughout study participation are eligible to participate.
- •Positive hepatitis C antibody test result at screening or within 3 months before starting the investigational intervention.
- •NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C Ribonucleic acid (RNA) test is obtained.
- •Participants with HCV infection who are currently on treatment, are eligible if they have an undetectable HCV viral load.
- •Has known human immunodeficiency virus (HIV) seropositive status, or positive HIV antibody test at screening.
- •For participants with unknown HIV status, HIV testing will be performed at screening unless prohibited by local regulations.
- •HIV-infected participants on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this study.
- •Treatment with: a) Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks before the start of treatment for the pharmacokinetic period.
- •b) Any coagulation-active drug (ie, non-steroidal anti-inflammatory drugs at doses know to have anticoagulant effects, warfarin, coumarin derivatives, platelet aggregation inhibitors) within 1 week before the start of the treatment for the bleeding episode or surgery, or as a planned or expected medication during the period from Day 1 until 24 hours (ie, 1 day) after the last Fibrogen-I infusion.
- •c) Participants receiving immune-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to greater than 10 mg per day), or similar drugs at the start of treatment for the pharmacokinetic period.
- •Documented medical history or current evidence of before the start of treatment for the pharmacokinetic period: Deep vein thrombosis or pulmonary embolism within 1 year.
- •Arterial thrombosis within 1 year.
- •Current evidence of oesophageal varicose bleeding.
- •Current evidence of end-stage liver disease (ie, Child-Pugh score B or C).
- •Polytrauma 1 year before the start of treatment for the bleeding episode or surgery.
- •Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or at any time before the start of treatment for the pharmacokinetic period.
- •Suspicion of an anti-fibrinogen inhibitor may be indicated by previous in vivo recovery, if available, of less than 0.5 (mg per dL) per (mg per kg), only if available.
- •Received an investigational intervention or used an invasive investigational medical device within 30 days or 5 half-lives before the first dose of study intervention, whichever is longer.
- •History of drug or alcohol abuse according to medical history assessment by the investigator within 1 year before the start of treatment for the pharmacokinetic period.
- •Documented medical history of uncontrolled, clinically significant intercurrent medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
结局指标
主要结局
To demonstrate the haemostatic efficacy of
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
Fibrogen-I for the first documented bleeding
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
episode in participants with congenital
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
fibrinogen deficiency requiring on-demand
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
treatment of acute bleeding (spontaneous or
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
after trauma)
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
To determine the single-dose pharmacokinetics of Fibrogen-I in
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
participants with congenital fibrinogen
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
deficiency.
时间窗: Day 1, Immediately prior to the scheduled infusion | Day 1, 1 hour post-infusion | Day 1, 3 hour post-infusion | Day 2, 24 hour post-infusion | Day 4, 72 hours post-infusion | Day 7, 144 hours post-infusion | Day 10, 216 hours post-infusion | Day 14, 312 hours post-infusion
次要结局
- To characterize further the efficacy of(Fibrogen-I in participants with congenital)
研究者
Dr Naman Shah
Lambda Therapeutic Research Ltd