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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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Abstract
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.
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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
Abstract
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.
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The Efficacy of Ferumoxytol for Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials
Shao Y, Luo W, Xu H, Zhang L, Guo Q
Acta haematologica. 2019;:1-7
Abstract
INTRODUCTION This systematic review and meta-analysis aims to explore the influence of ferumoxytol versus placebo on iron deficiency anemia. METHODS We search for randomized controlled trials (RCTs) assessing the effect of ferumoxytol on iron deficiency anemia on PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. This meta-analysis is performed using the random-effects model. RESULTS Four RCTs are included in the meta-analysis. Compared with the control group for iron deficiency anemia, intravenous ferumoxytol can significantly improve the proportion of patients with a ≥20 g/L hemoglobin (Hb) increase (RR = 18.43; 95% CI = 7.29-46.57; p < 0.00001), the proportion of patients with an Hb level ≥120 g/L (RR = 18.55; 95% CI = 8.66-39.72; p < 0.00001), transferrin saturation (mean difference = 11.08; 95% CI = 9.86-12.31; p < 0.00001) and FACIT-fatigue score (mean difference = 4.60; 95% CI = 3.21-6.00; p < 0.00001), but has no remarkable influence on adverse events (RR = 1.33; 95% CI = 0.84-2.10; p = 0.22), serious adverse events (RR = 1.22; 95% CI = 0.74-2.02; p = 0.44), and death (RR = 0.32; 95% CI = 0.05-1.95; p = 0.22). CONCLUSIONS Intravenous ferumoxytol can provide the important benefits for iron deficiency anemia.
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Efficacy of immunosuppressive therapy in children with acquired aplastic anemia
Wang SC, Zou Y, Chen XJ, Yang WY, Liu TF, Zhang L, Chen YM, Guo Y, Zhu XF
Chinese Journal of Pediatrics. 2009;47((1):):53-6.
Abstract
OBJECTIVE This study was designed to evaluate the efficacy of immunosuppressive therapy (IST) regimens as treatment of children with acquired severe aplastic anemia (SAA). METHODS Data of consecutive 112 children with SAA who had no HLA-matched sibling seen from January 2000 to June 2006 were retrospectively analyzed. The patients were randomized to receive one of the following IST regimens: cyclosporine A (CSA) alone (IST regimen I); CSA and intravenous immunoglobulin (IVIG) [400 mg/(kg x d) x 5 d] (IST regimen II); rabbit anti-T-lymphocyte globulin (R-ATG) [3-5 mg/(kg x d) x 5 d] and CSA (IST regimen III). No repeated courses of R-ATG were given for nonresponders. All the patients also received stanozolol or testosterone propionate. The dose of CSA was adjusted to maintain trough drug levels above 100 microg/L and peak drug levels above 300 microg/L. RESULTS The overall rate of response to IST regimen I was 26. 92% and to IST regimen II was 33. 33%. The response to IST regimen III (62. 5%) was significantly higher (P = 0. 001). The response to IST regimen I and IST regimen II had no significant difference. The 5-year overall survival for IST regimens I, II, and III was 20. 50% +/- 15. 41%, 39. 77% +/- 9. 77%, and 66. 27% +/- 6. 84%, respectively. CONCLUSION If patients had no HLA-matched sibling, the combination of R-ATG and CSA remains the best combination for the treatment of children with SAA, providing a survival advantage at 5 years.