A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects

Abstract

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72hr washout and 5-11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE®. 39 inhibitor-negative males with SHA (FVIII:C<2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3hr clinic visit 24hr-post home infusion of FVIII and then 3hr-post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and VWF:Ag were determined; and PK parameters were analyzed using the ADVATE® myPKFiT® dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6-point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared to the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE®.

[Retracted] Correlation Analysis of DNA Methylation in the von Willebrand Factor Promoter Region and the Risk of Unexplained Recurrent Hemophilia: Systematic Review and Meta‐Analysis

“…But there are still about 50% of patients with unknown causes, unable to target the cause of treatment and plaguing patients. Studies have shown that screening for thrombotic genes is effective in preventing unexplained recurrent abortions [ 9 ]. Coagulation factor vWF is a serine protease synthesized by the liver and plays an important role in fibrinolysis and coagulation.…”

Limited sampling strategies for individualized BAX 855 prophylaxis in severe hemophilia A: in silico evaluation

“…[13] Furthermore, the study of Blanchette et al compared a 6-sample design to a 2-sample design in a PK study of Advate with 39 patients with hemophilia A, and concluded that the 2-sample design showed su cient accuracy to be used in routine clinical care. [29] This conclusion was based on an substantial and almost perfect interclass correlation for clearance (0.73) and t1/2 (0.84) between the PK parameters in the 6-and 2sample design. Though, it should be noted that the PK parameters calculated with a 6-sample design are not the exact (true) individual PK parameters, making the agreement of the 2-sample design with true individual PK parameters smaller.…”

A personalized limited sampling approach to better estimate terminal half‐life of FVIII concentrates

“…Personalized LSA can be used to ask for a patient to come back to clinic a few days later, however this may not be optimal as it will add one extra clinic visit. To prevent extra visits, it is possible to perform a two‐sample protocol: during one unique clinic visit, one sample is obtained at trough—shortly before infusion of FVIII; and one sample is obtained at peak—shortly after the same infusion of FVIII 10,13 . Personalized LSA can leverage a previous PK assessment and derive the sampling time of trough for such two‐sample protocols.…”