Efficacy, safety and bioequivalence of the human-derived B-domain-deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients
Xi Y, Jin C, Liu W, Zhou H, Wang Z, Zhou R, Lou S, Zhao X, Chen F, Cheng P, et al
Haemophilia : the official journal of the World Federation of Hemophilia. 2022
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INTRODUCTION Current treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma-derived FVIII is short in China. PURPOSE To evaluate the efficacy and safety of a new B-domain deleted (BDD) recombinant FVIII (TQG202) produced by human-derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha. METHODS This multicentre, clinical trial consisted of an open-label, randomized, two-period cross-over trial assessing single-dose pharmacokinetics (PK), and a single-arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single-dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded. RESULTS Twenty-six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2-2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was .027 (95% CI: .026-.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors. CONCLUSION TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice.
Effects of circuit albumin coating on coagulation and inflammatory response for patients receiving aortic arch replacement: a randomized controlled trial
Chen L, Lv L, Long C, Lou S
OBJECTIVE To investigate whether human serum albumin coating before cardiopulmonary bypass (CPB) could improve platelet function and hemostasis and mitigate the inflammatory response among patients receiving aortic arch replacement with deep hypothermic circulatory arrest (DHCA). METHODS Sixty patients were included and randomized into two groups: the Control Group (CG, receiving 40 g human albumin 5 minutes after the initiation of CPB) and the Study Group (SG, circulating the prime with 40 g albumin for 5 minutes before CPB). Rapid thromboelastography, complete blood count, coagulation tests and cytokines (IL-1, IL-6, IL-10, TNF-alpha and PAF) were measured at two intervals: after anesthesia induction and before CPB (T1) and 10 minutes after heparin reversal before any blood product transfusion (T2). RESULTS Compared with T1, the fibrinogen and MA levels in both groups reduced significantly after heparin reversal and fell within the normal range for most patients. The platelet count reduction (DeltaPLT) in the Study Group was significantly less than in the Control Group (p=0.031). Despite the inflammatory factor levels increasing after CPB (p<0.001), no differences were found between the Control Group and the Study Group. Fewer red blood cells were given in the Study Group, but this was not significant (p=0.05). CONCLUSION Most patients receiving aortic arch replacement with DHCA have normal platelet function and fibrinogen levels after heparin reversal. Albumin coating before CPB may mitigate the platelet count reduction, but not platelet dysfunction. There is a trend that the patients treated with albumin coating received less red blood cell transfusions.