A MULTICENTRE PROSPECTIVE OPEN-LABEL STUDY ASSESSING PHARMACOKINETICS, CLINICAL EFFICACY AND SAFETY OF A TRIPLE-SECURED FIBRINOGEN CONCENTRATE: FIBRINOGENE T-I
Abstract number: P-M-196
Négrier1 C., Borg2 J., Claeyssens3 S., De Moerloose4 P., Dreyfus5 M., Goudemand6 J., Gruel7 Y., Peyvandi8 F., Rothschild9 C., Alessi10 M., Scherrmann11 J., Waegemans12 T., Padrazzi12 B.
11Haemophilia Treatment Center, Hôpital E. Herriot, Lyon 1010Laboratory of Haematology, Hôpital La Timone, Marseille 1111Pharmacokinetic Department, Université René Descartes, Paris 1212Clinical Development Department, LFB, Les Ulis, France 22Haemostasis Laboratory, Centre Hospitalier Régional et Universitaire, Lille 33Haemophilia Treatment Center, Hôpital Purpan, Toulouse, France 44Haemostasis Unit, Hôpital Universitaire, Genève, Switzerland 55Laboratory of Haematology, Hôpital Bicêtre, Le Kremlin Bicêtre 66Haemophilia Treatment Center, Centre Hospitalier Régional et Universitaire, Lille 77Haemostasis Laboratory, Faculté de Médecine, Tours, France 88Haemophilia Treatment Center, Haemophilia and Thrombosis Center, Milan, Italy 99Haemophila Center F. Josso, Groupe Hospitalier Necker-Enfants Malades, Paris
How-to-cite Négrier C, Borg J, Claeyssens S, De Moerloose P, Dreyfus M, Goudemand J, Gruel Y, Peyvandi F, Rothschild C, Alessi M, Scherrmann J, Waegemans T, Padrazzi B. A MULTICENTRE PROSPECTIVE OPEN-LABEL STUDY ASSESSING PHARMACOKINETICS, CLINICAL EFFICACY AND SAFETY OF A TRIPLE-SECURED FIBRINOGEN CONCENTRATE: FIBRINOGENE T-I. J Thromb Haemost 2007; 5 Supplement 2: P-M-196
Abstract
Introduction: FIBRINOGENE T-I is a new plasma-derived fibrinogen concentrate the manufacturing process of which includes solvent-detergent treatment, 35nm nanofiltration and dry-heat treatment. Pharmacokinetics, clinical efficacy and safety were assessed in patients with inherited afibrinogenemia.
Methods: Six adult afibrinogenemic patients were enrolled in a multi-centre phase I/II study. Fibrinogen activity and antigen were measured in 5 patients over 14 days following a single infusion of 60 mg/kg, as well as routine coagulation parameters as surrogates for clinical efficacy. Efficacy to treat bleeding episodes was assessed using a 4-point scale. Safety was evaluated via clinical and laboratory adverse events. Descriptive statistics were used.
Results: The timecourse of fibrinogen plasma levels (activity and antigen) exhibited a mono-exponential decay with low inter-patient variability. Fibrinogen activity and antigen measurements were similar and highly correlated. Mean ( SD) half-life was 828 hours and in vivo recovery 9412%. Distribution volume was 3.60.6 l and clearance 315 ml/h. Normalization of coagulation assays was achieved in all patients for at least 24 hours.
Twenty-one bleeding episodes occurred in 4 patients. The efficacy was rated as excellent or good in 20 cases. A single dose was infused in 19 cases and overall the mean dose administered was 50 mg/kg. No serious adverse events related to the study drug were reported.
Conclusions: FIBRINOGENE T-I pharmacokinetics are consistent with the expected profile. The safety and efficacy profile is excellent in specifically restoring haemostasis and treating bleeding episodes in afibrinogenemic patients.
