An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A
The Phase I/III study is an open-label, non-randomized, efficacy, safety and PK study comparing octocog alfa and CSL Behring's recombinant factor VIII-SingleChain (rVIII-SC). The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK section (Part 3) including a surgical sub-study for subjects enrolled in Parts 2 and 3.
In Part 1 of the study, subjects will receive a single infusion of 50 IU/kg of octocog alpha followed by a single infusion of 50 IU/kg of rVIII-SC. In Parts 2 and 3 of the study, subjects will receive infusions of rVIII-SingleChain to prevent and treat bleeding (if required), at a dose and frequency determined by their study doctor (based on the subject's underlying bleeding phenotype).
Recombinant factor VIII (rFVIII) consists of two linked protein chains – a heavy one and a light one. Under certain conditions, these chains can dissociate, resulting in the formation of separated, or "dissociated," rFVIII chains. The CSL Behring rVIII-SingleChain uses a strong, covalent bond that connects the light and heavy chains, thereby creating a single chain rFVIII.
In-house studies have shown that the molecular integrity of rFVIII is significantly increased using the single-chain design, resulting in a homogenous product that is more stable than currently available FVIII products. In addition, in-vitro studies have shown that rVIII-SingleChain demonstrates a very strong affinity for von Willebrand factor, resulting in a faster and more efficient binding to VWF. The FVIII/VWF complex plays an important role in the physiological activity and clearance of FVIII and has been shown to have an influence on the presentation of FVIII to the immune system.
More information about the study design can be found at
12/31/2013 5:04 PM