A cross-over pharmacokinetic study of a double viral inactivated factor IXconcentrate (15 nm filtration and SD) compared to a SD factor IX concentrate

A double blind randomized cross-over multi-center study has been conducted to compare the pharmacokinetic and coagulation activation markers of high-p urity factor IX concentrate subjected to both solvent/detergent (SD) treatm ent and 15 nm-filtration (FIX-SD-15) with the licensed product subjected on ly to solvent-detergent (FIX-SD). This filtration process allows the elimin ation of small particles, such as non-enveloped viruses (i.e., hepatitis A and parvovirus B19). Eleven severe hemophilia B patients (FIX coagulant act ivity <2 IU/dl) received one infusion of 60 IU/kg of FIX-SD and one infusio n of 60 IU/kg of FIX-SD-15 at least at 10 days interval. Blood samples were obtained before and at various time up to 72 h after infusion. The decay c urves of factor IX (FIX:C and FIX:Ag) were evaluated by a model independent method. Bioequivalence was found between the two concentrates using the Sc huirmann test. The mean FIX:C and FIX:Ag recovery of FIX-SD-15 was 1.08 and 0.89 IU/dl/IU/kg respectively with a mean half-life of 33.3 h for FIX:C an d 25.6 h for FIX:Ag. Six months after initial enrollment, pharmacokinetic p arameters were similar in the 7 patients tested. There was no significant v ariation of prothrombin fragment 1+2 and thrombin-antithrombin complexes me asured up to 6 h after infusion, indicating that there was no activation pr ocess after administration of FIX. In conclusion, these data demonstrate th at the introduction of a 15 nm filtration does not alter the pharmacokineti c profile of a well characterized SD FIX concentrate while providing additi onal viral safety.