Pharmacokinetic results of two studies with a novel fibrinogen concentrate in subjects with afibrinogenaemia.
W. Stevens1, A. Bellon1, F. Bridey1, Ph. de Moerloose2 (1Les Ulis, France, 2Geneva, Switzerland)
Bleeding disorders, coagulation and fibrinolytic factors
Time: 17:15 - 18:15
Objective: A second generation of plasma-derived human fibrinogen concentrate, named FibCLOT®/ CLOTTAFACT® (Human Fibrinogen) (1.5 g/100 ml) has been developed. The product recovered from the supernatant fraction of cryoprecipitate using an ethanol fractionation, includes 3 viral safety steps: solvent-detergent treatment, nanofiltration and dry heat (80°C during 72 hours). Two prospective clinical trials (French and multinational) were conducted consecutively including a total of 26 patients with afibrinogenaemia (6 + 20). Among them, 19 patients, with the average weight of 68 kg, participated in the pharmacokinetic parts of the studies (5 children or adolescents of more than 40 kg and 14 adults). This abstract focuses only on the pharmacokinetic outcome of these two studies.
Methods: In the two studies, pharmacokinetic assessment was performed after a single infusion of 0.06 g/kg of FibCLOT® / CLOTTAFACT®. Concentration of fibrinogen expressed in antigen and activity were followed during 14 days after infusion. These parameters values are presented using geometric mean values.
Results: Pharmacokinetic studies showed that the maximum concentration was observed at the first available time-point (at about 1 hour) and was followed by a slow mono-exponential decrease, reaching the critical haemostatic plasma fibrinogen level of 0.5 g/L in about 3 to 4 days, with no notable differences when the data were stratified by age or by gender. In both studies, incremental recovery was 23.5 g/L per g/kg fibrinogen infused. In addition the pharmacokinetic profiles of fibrinogen antigen and activity are superimposed showing that the FibCLOT® / CLOTTAFACT® manufacturing process preserves the functional properties of fibrinogen.
Conclusion: CLOTTAFACT® / FibCLOT® shows consistent pharmacokinetic properties in the 19 afibrinogenaemic patients included in two different studies. Our results from two clinical studies conducted separately, demonstrate that an infusion of 3 g of FibCLOT® / CLOTTAFACT® increases plasma fibrinogen level by 1 g/L in a 70 kg person.