Rviii-Singlechain Pharmacokinetics And Safety In Children Less Than 12 Years Of Age

Background: rVIII-SingleChain, a novel recombinant Factor VIII (rFVIII), has been designed as a B-domain truncated construct with a covalent bound between the heavy and light chain, aiming for a higher binding affinity to von Willebrand Factor (vWF). A currently ongoing study is investigating the pharmacokinetics, efficacy and safety of rVIII-SingleChain in children Methods: The study has been approved by the relevant Ethics committee and national authorities and is conducted according to GCP and the Declaration of Helsinki. A total of 84 subjects have been enrolled into the study, 35 of them in the 0 to Results: The PK results reported in the younger children (0- 1/2 , 5.07 mL/h/kg for CL, 12.4 h for MRT and 1077 IU*h/dL for AUC inf . In the older children (6- 1/2 , 4.63 mL/h/kg for CL, 12.3 h for MRT and 1167 IU*h/dL for AUC inf . At the time of data cut, the study accumulated a total of 3651 exposure days (EDs) with 30 patients reaching u003e 50 EDs and 6 patients reaching u003e100EDs. No patient developed an inhibitor after exposure to rVIII-SingleChain. The rate of non-inhibitory anti-drug antibody formation was in line with recently published trials investigating novel rFVIII products. The most commonly observed AEs were nasopharyngitis and rhinitis. A total of 10 SAEs were reported in 7 patients the study so far, of which none was judged to be related by the investigators. Conclusion: The increased binding of rVIII-SingleChain to vWF translates into favorable pharmacokinetics without the need for glycopegylation or fusion to antibody fragments. Expectedly, mean t 1/2 was shorter and mean CL greater in children when compared to adults and adolescents. rVIII-SingleChain demonstrated a very positive safety profile in this clinical study in children aged 0 to 12 years with severe hemophilia A. Disclosures Bensen-Kennedy: CSL Behring: Employment. St. Ledger: CSL Behring: Employment. Limsakun: CSL Behring: Employment. Veldman: CSL Behring: Employment. Pabinger: Bayer: Membership on an entity9s Board of Directors or advisory committees; Baxter: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees; CSL Behring: Membership on an entity9s Board of Directors or advisory committees, Other: Travel support, Research Funding; Boehringer Ingelheim: Membership on an entity9s Board of Directors or advisory committees; Amgen: Membership on an entity9s Board of Directors or advisory committees; GSK: Membership on an entity9s Board of Directors or advisory committees.