E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Surgical procedures in patients with afibrinogenaemia and severe hypofibrinogenaemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052651 |
E.1.2 | Term | Afibrinogenaemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051125 |
E.1.2 | Term | Hypofibrinogenaemia |
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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 |
The primary objective of the study is to assess the efficacy of FIBRINOGENE T-I administered for peri-operative prophylaxis of bleeding during surgery in patients with afibrinogenaemia or severe hypofibrinogenaemia. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: - to document the clinical postoperative healing of the patients, - to assess the safety of FIBRINOGENE T-I in patients with afibrinogenaemia or hypofibrinogenaemia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent form 2. Inherited afibrinogenaemia defined as no detectable plasma fibrinogen or severe hypofibrinogenaemia defined as plasma fibrinogen activity < or = 0.5 g/l 3. 65 years ≥ Age ≥ 12 years 4. Known serological status (including vaccinations) 5. Requiring replacement therapy before elective surgery 6. Covered by healthcare insurance in accordance with local requirements 7. Medically acceptable form of birth control for women of childbearing potential |
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E.4 | Principal exclusion criteria |
1. Dysfibrinogenemia or acquired fibrinogen deficiency 2. Antibodies against fibrinogen or fibrinogen inhibitor 3. Surgery requiring fresh frozen plasma 4. History of venous or arterial thrombosis 5. Patient presenting any one of the following indicators of thrombophilia or associated bleeding disorders: - Activated protein C resistance control /patient < 1.8 - FVIII:C level < 50 IU/dl - FIX:C level < 60 - FXII:C level < 60 IU/dl - FXI < 60 IU/dl- VWF:RCo level < 50 IU/dl - Prothrombin Time < 70 % - Bleeding time > 9 minutes (standardised Ivy incision) - Thrombin Time > 17 seconds - Lupus anticoagulant (LA-aPTT) patient/control > 1.55 - Dilute Russell's Viper Venom Time (LA-dRVVT) patient/control > 1.3 6. Platelets less than 100G/l 7. AST and ALT > 5 times the upper limit of normal 8. Known history of hypersensitivity or other severe reaction to any component of the investigational medicinal product 9. Patient presenting renal insufficiency or diabetes 10. Treatment with any other investigational medicinal product 11. Previously included in this study for the same procedure 12. Drug or alcohol abuse 13. Inability to tolerate the required fluid infusion volume according to the Investigator’s judgement 14. Patient whose use of concomitant medication may interfere with the interpretation of data 15. Patient with abnormalities on physical examination or laboratory results that, in the opinion of the Investigator, are deemed to be clinically significant 16. Severe comorbidity that in the opinion of the Investigator could jeopardise patient’s safety 17. Pregnancy or breastfeeding 18. Anticipated poor compliance with study procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point to assess efficacy is the 4-point scale defined as follows: - Excellent: clinical normalisation of haemostasis, i.e. comparable to a patient with no bleeding disorder - Good: mildly increased bleeding compared to a patient with no bleeding disorder - Moderate: moderately increased bleeding compared to a patient with no bleeding disorder - None: severely increased bleeding compared to a patient with no bleeding disorder |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |