E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congenital fibrinogen deficiency (afibrinogenemia, severe hypofibrinogenemia) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016075 |
E.1.2 | Term | Factor I deficiency |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of Fibrinogen Concentrate (Human) (FCH) administration by adequately controlling acute bleeding (spontaneous or after trauma) compared to the hemostatic efficacy data in the historical control on cryoprecipitate treatment from retrospective physician survey. |
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E.2.2 | Secondary objectives of the trial |
- To show an association between the overall clinical assessment of hemostatic efficacy and the surrogate endpoint “clot strength” (referred to as maximum clot strength or clot firmness [MCF] in this protocol), also termed “clot firmness”, that was used as a surrogate endpoint for hemostatic efficacy, and was determined via rotational thromboelastometry (ROTEM) in the pivotal pharmacokinetic (PK) study BI3023_2001 conducted by CSL Behring. Therefore MCF as surrogate efficacy parameter will be determined prior to and 60 minutes after each infusion. - To elevate fibrinogen plasma levels 60 minutes post infusion to a peak target level of 100 mg/dL with an accepted lower limit of 80 mg/dL for minor bleeds, and to a peak target level of 150 mg/dL with an accepted lower limit of 130 mg/dL for major bleeds. - To determine the response in subjects with congenital fibrinogen deficiency (in vivo recovery [IVR]) - To document the safety of FCH administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Male or female, any age. · Documented congenital fibrinogen deficiency, expected to require treatment for bleeding: - Fibrinogen deficiency manifested as afibrinogenemia or severe hypofibrinogenemia (plasma fibrinogen level <50 mg/dL). - Plasma fibrinogen activity <50 mg/dL and fibrinogen antigen <1.2 times the plasma fibrinogen activity at screening or previously confirmed in Study BI3023_2001. If plasma fibrinogen activity at screening is undetectable, the fibrinogen antigen at screening must be <20 mg/dL. For those subjects who present to the clinic with an acute bleed without having had a screening visit and who are known to have either afibrinogenemia or severe hypofibrinogenemia (confirmation from medical record or verbal communication to be recorded in source documents), the plasma fibrinogen activity and antigen is to be determined at the CSL Behring laboratory with blood drawn on the day of enrolment (Day 1) and in a non-bleeding state on Day 45, as would have been done at screening. · Presenting with an episode of acute bleeding (either spontaneous or after trauma) not requiring surgery. · Provide a signed informed consent (from the subject or their legally authorized representative). A screening informed consent form is to be signed by all subjects who participate in the screening visit and a study informed consent is to be signed by all subjects on Day 1 prior to any study activities.
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E.4 | Principal exclusion criteria |
· Life expectancy <6 months. · Bleeding disorder other than congenital fibrinogen deficiency, but including dysfibrinogenemia. · Treatment with: - Any IMP in the 30 days prior to enrollment (Day 1). - Any fibrinogen concentrate or other fibrinogen containing blood product in the 2 weeks prior to screening and the 2 weeks prior to enrollment (Day 1). - Any coagulation active drug (i.e. non-steroidal-antirheumatics, warfarin, cumarin derivates, platelet aggregation inhibitors) in the 2 weeks prior to screening, the 2 weeks prior to enrollment (Day 1), or as a planned or expected medication during the time period from Day 1 until 24 hours after the last FCH infusion. · Presence or history of: - nHypersensitivity to FCH. - Deep vein thrombosis or pulmonary embolism within 1 year prior to enrollment. - Arterial thrombosis within 1 year prior to enrollment. - Hypersensitivity to human plasma proteins. · History or presence of esophageal varicose bleeding. · End stage liver disease (i.e. Child Pugh score B or C). · Planned or expected surgery (i.e. for bleedings from aneurysm or splenic rupture). · Pregnancy, or an intention to become pregnant during the study. · Currently breast-feeding, or with the intention of breast-feeding during the study. · Human immunodeficiency virus (HIV) positive. · Polytrauma, present or within 6 months prior to enrollment. · Suspicion of an anti fibrinogen inhibitor as indicated by previous IVR (there is no test on inhibitors), if available (<0.5 (mg/dL)/(mg/kg)). · Previous inclusion and treatment in the prospective part of the study. · Participation in any clinical study in the 30 days prior to enrollment.
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E.5 End points |
E.5.1 | Primary end point(s) |
·Bleeding (spontaneous or trauma-related) that requires intervention |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
historically controlled (single group assignment) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |