Trenonacog alfa治疗儿童血友病B的安全性、有效性和药代动力学

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-01-01 DOI:10.1016/j.rpth.2024.102655

Kateryna Vilchevska , Can Balkan , Valentin Turea , Darejani Gurtchumelia , Alessandra Nunes Loureiro Prezotti , Luciana Correa Oliveira de Oliveira , Julissa Leon , Mark Fosdal , Johnny Mahlangu

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引用次数: 0

摘要

背景：trenonacog alfa是一种重组因子IX，已被批准用于青少年和成人B型血友病患者。目的：本研究的目的是评估trenonacog alfa在既往治疗的12岁重度或中重度B型血友病患者中的药代动力学（PK）、预防疗效、出血发作控制和安全性。方法研究分为3个阶段：(1)单次输注75±5 IU/kg后的PK评估，(2)治疗阶段，参与者接受35至75 IU/kg的trenonacog alfa预防治疗，持续50天暴露，(3)继续治疗阶段，预防治疗可以再进行≥50天暴露。结果除清除率较高、平均停留时间和消除半衰期较短、增量恢复较低外，青少年与成人的钾代动力学具有可比性。在联合治疗和继续治疗阶段，预防导致中位年出血率为0.86（平均= 2.34）；33.3%的参与者没有出血；经1 ~ 2次输液后，83.7%的出血量得到缓解。一个不良事件可能与trenonacog α有关，这是一种导致研究早期终止的非严重超敏反应。trenonacog alfa在既往治疗过的儿科患者中用于预防和出血治疗的有效性和安全性与成人和青少年的报道一致。6岁和6至12岁的受试者的结果似乎没有重要的临床差异。结论trenonacog是治疗儿童B型血友病的理想选择。

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Trenonacog alfa safety, efficacy, and pharmacokinetics in previously treated pediatric hemophilia B

Background

Trenonacog alfa is a recombinant factor IX approved for adolescents and adults with hemophilia B.

Objectives

The aim of this study was to assess the pharmacokinetics (PK), efficacy as prophylaxis, control of bleeding episodes, and safety of trenonacog alfa in previously treated participants aged <12 years with severe or moderately severe hemophilia B and no current or history of inhibitors.

Methods

The study had 3 phases: (1) PK evaluation after a single infusion of 75 ± 5 IU/kg, (2) treatment phase in which participants received trenonacog alfa prophylaxis 35 to 75 IU/kg for 50 exposure days, and (3) a continuation phase in which prophylaxis could be administered for ≥50 additional exposure days.

Results

The PK of trenonacog alfa was comparable between adolescents and adults except for higher clearance, shorter mean residence time and elimination half-life, and lower incremental recovery. Prophylaxis resulted in a median annualized bleeding rate of 0.86 (mean = 2.34) for the combined treatment and continuation phases; 33.3% of participants had zero bleeds; and 83.7% of bleeds treated resolved with 1 or 2 infusions. One adverse event was possibly related to trenonacog alfa, a nonserious hypersensitivity reaction leading to early study termination. The efficacy and safety of trenonacog alfa for prophylaxis and bleeding treatment in previously treated pediatric participants were consistent with those reported for adults and adolescents. There appeared to be no clinically important differences between the results for participants aged <6 years and those aged 6 to <12 years.