Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.
Xalnesiran，一种靶向乙型肝炎病毒（HBV）基因组保守区域的微小干扰 RNA 分子，可沉默多个 HBV 转录本，可能对慢性 HBV 感染患者具有疗效，无论是否与免疫调节剂联合使用。

We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.05 IU per milliliter) at 24 weeks after the end of treatment. Safety was also assessed.
我们进行了一项 2 期、多中心、随机、对照、适应性、开放标签的平台试验，包括评估慢性乙型肝炎病毒感染者在使用 NA 疗法实现病毒学抑制的情况下，接受 100 毫克（组 1）、200 毫克（组 2）、200 毫克加 150 毫克鲁佐托利莫德（组 3）、200 毫克加 180 微克聚乙二醇化干扰素α-2a（组 4）或单独使用核苷酸或核苷酸类似物（NA）（组 5）治疗 48 周的效果。主要疗效终点是治疗结束后 24 周时乙型肝炎表面抗原（HBsAg）消失（HBsAg 水平，每毫升<0.05 IU）的情况。同时评估了安全性。

Among 159 participants (30, 30, 34, 30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval [CI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5. In groups 1 through 5, respectively, HBsAg seroconversion occurred in 3%, none, 3%, 20%, and none of the participants at 24 weeks after the end of treatment. HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter. In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17%, 10%, 18%, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level.
在 159 名参与者（第 1 组至第 5 组分别为 30、30、34、30 和 35 人）中，主要终点事件在第 1 组中占 7%（95%置信区间[CI]为 1 至 22），在第 2 组中占 3%（95% CI 为 0 至 17），在第 3 组中占 12%（95% CI 为 3 至 28），在第 4 组中占 23%（95% CI 为 10 至 42），而在第 5 组中则没有（95% CI 为 0 至 10）。在第 1 组至第 5 组中，分别有 3%、无、3%、20%和无人于治疗结束后的 24 周出现 HBsAg 血清转换。仅 HBsAg 水平低于每毫升 1000 IU 的参与者出现 HBsAg 损失，无论是否发生血清转换。在第 1 组至第 5 组中，分别有 17%、10%、18%、50%和 6%的参与者出现 3 级或 4 级不良事件，最常见的事件是丙氨酸转氨酶水平升高。

Among participants with chronic HBV infection who had virologic suppression with NA therapy, treatment with xalnesiran plus an immunomodulator resulted in HBsAg loss at 24 weeks after the end of treatment in a substantial percentage of participants. Grade 3 or 4 adverse events were not uncommon. (Funded by F. Hoffmann–La Roche; Piranga ClinicalTrials.gov number, NCT04225715.)
在纳鲁那疗法实现病毒学抑制的慢性乙型肝炎病毒感染参与者中，接受 xalnesiran 联合免疫调节剂治疗，在治疗结束后 24 周内，相当一部分参与者出现了 HBsAg 损失。3 级或 4 级不良事件并不罕见。（由 F. Hoffmann–La Roche 资助；Piranga 临床试验.gov 编号，NCT04225715。）