Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials.

We previously conducted a pilot study demonstrating the safety and efficacy of AAV-factor IX (FIX) Padua gene therapy (BBM-H901) in ten male participants with hemophilia B.

我们之前进行了一项初步研究，证明了使用腺相关病毒（AAV）-凝血因子IX（FIX）Padua基因治疗（BBM-H901）在十名患有血友病B的男性参与者中的安全性和有效性。

Here we report a single-arm dose-escalation phase 1/2 trial in 6 male participants and a multicentre phase 3 trial in 26 participants with hemophilia B in China.

我们报告了一项单臂剂量递增的1/2期试验，共有6名男性参与者，以及在中国进行的一项涉及26名血友病B患者的多中心3期试验。

The phase 1/2 study tested a dose of 5 × 1012 vg kg-1 (n = 6), with primary endpoints assessing dose-limiting toxicities (DLT) and adverse events (AEs).

1/2期研究测试了5 × 10^12 vg kg^-1的剂量（n=6），主要终点评估剂量限制性毒性（DLT）和不良事件（AEs）。

The primary endpoint was met with no DLT observed in the 10 weeks postinfusion.

主要终点已达成，且在输液后10周内未观察到剂量限制性毒性（DLT）事件。

The most common drug-related AEs were transaminitis (33.3%), and no grade 3 drug-related AE occurred within 52 weeks postintervention.

最常见的药物相关不良事件是转氨酶升高（33.3%），并且在干预后52周内未发生任何3级药物相关不良事件。

The phase 3 study tested the 5 × 1012 vg kg-1 dose, as determined in the phase 1/2 study, in 26 patients.

III期研究在26名患者中测试了在I/II期研究中确定的5 × 10^12 vg kg^-1剂量。

The primary endpoint evaluated the annualized bleeding rate (ABR) after gene therapy and secondary endpoints included vector-derived FIX:C, target joint and percentage of participants with zero bleeds postgene therapy.

主要终点评估了基因治疗后的年化出血率（ABR），次要终点包括载体衍生的FIX:C、目标关节以及基因治疗后无出血的参与者百分比。

The study met its primary endpoint as the mean (95% confidence interval(CI)) ABR within 52 weeks after BBM-H901 infusion decreased to 0.60 (0.18-1.99), and the upper limit of the 95% CI (1.99) was lower than the predefined superiority margin of 5.0 (historical ABR assumed for patients receiving prophylactic FIX treatment in China).

该研究达到了其主要终点，因为在BBM-H901输注后52周内平均（95%置信区间（CI））ABR降低至0.60（0.18-1.99），且95%置信区间的上限（1.99）低于预设的优势边界5.0（假设接受预防性FIX治疗的中国患者的ABR历史值）。

In the phase 3 trial, the most common drug-related AEs were transaminitis as well, and the vector-derived FIX:C had a mean of 41.9 (28.7) IU dl-1 at week 52.

在III期试验中，最常见的与药物相关的不良事件也是转氨酶异常，而在第52周，载体衍生的FIX:C平均值为41.9（28.7）IU dl-1。

None of the participants had a target joint, and 80.8% of participants experienced zero bleeds during the 52-week follow-up.

在参与者中，没有人出现目标关节，且在52周的随访期间，80.8%的参与者没有出现任何出血事件。

Our study supports the safety and efficacy of AAV-FIX Padua gene therapy in a large Chinese cohort.

我们的研究支持AAV-FIX Padua基因疗法在中国大型队列中的安全性和有效性。

ClinicalTrials.gov registration: NCT05203679 .

临床试验注册：NCT05203679 .