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.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, et al
Journal of hematology & oncology. 2021;14(1):37
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
Sealing the Intramedullary Femoral Canal for Blood Loss in Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials
Wang K, Yuan W, An J, Cheng P, Song P, Li S, Jiang J, Zhou H
The journal of knee surgery. 2019
Blood loss after total knee arthroplasty (TKA) is a potentially serious medical problem since it leads to anemia, increased need for transfusion, and prolonged hospitalization. Some studies have reported that sealing of the intramedullary femoral canal during TKA may decrease postoperative blood loss. The purpose of this study is to determine the effects of sealing of the intramedullary femoral canal during TKA on blood loss and transfusion rate. Electronic databases, PubMed, EMBASE, the Cochrane Library, Web of Science, and Chinese Biomedical Database, were systematically searched. Only randomized controlled trials (RCTs) that compared the sealing group with the control group during TKA were included up to March 2019. Two reviewers independently extracted data and assessed the quality of included studies. The statistical analysis was performed by using Review Manager 5.3 software. Cochrane Risk of Bias tool was used for quality assessment. Overall, eight RCTs involving 996 patients met our criteria and were analyzed. The results of meta-analysis showed that patients in the sealed group had less total blood loss, less total drain output and less hidden blood loss, less transfusion rates, a lower drop of hemoglobin level at day 1 postoperatively, and less hematoma than the control group. On the other hand, there were no significant differences in infection, deep vein thrombosis, and redness of incision between sealed and control group. Current meta-analysis found that sealing the femoral canal during TKA was an effective method for the control of blood loss.