Elebsiran and PEG-IFNα for chronic hepatitis B infection: a partially randomized, open-label, phase 2 trial.

Here we provide a randomized evaluation of the small interfering RNA elebsiran, in combination with pegylated interferon alfa (PEG-IFNα), compared with PEG-IFNα monotherapy.

在这里，我们提供了一项随机评估，将小干扰RNA elebsiran与聚乙二醇干扰素α(PEG-IFNα)联合使用，与单独使用PEG-IFNα进行比较。

In addition, this study evaluates the potential role of the HBV therapeutic vaccine BRII-179 in identifying immunologically responsive patients and improving hepatitis B surface antigen (HBsAg) loss rates.

此外，本研究评估了乙型肝炎治疗性疫苗BRII-179在识别免疫应答患者和提高乙型肝炎表面抗原(HBsAg)清除率方面的潜在作用。

In part I (cohorts 1-3), virally suppressed participants with chronic HBV infection naive to BRII-179 were randomized 1:1:1 to receive 48 weekly doses of PEG-IFNα alone or in combination with 13 doses of elebsiran (200 mg or 100 mg) administered every 4 weeks.

在第一部分（队列1-3），对慢性乙型肝炎病毒(HBV)感染且未使用过BRII-179的病毒抑制患者进行了随机分组，按照1:1:1的比例分别接受每周一次的PEG-IFNα单药治疗或与每4周一次的elebsiran（200毫克或100毫克）联合治疗，共48周。

In part II (cohort 4), participants who had previously received 9 doses of elebsiran and BRII-179 in a prospective study (BRII-179-835-001) were categorized as BRII-179 anti-HBs responders or nonresponders based on their peak hepatitis B surface antibody (anti-HBs) levels (≥10 IU l-1 or <10 IU l-1, respectively) and subsequently received 13 doses of elebsiran 100 mg every 4 weeks plus 48 weekly doses of PEG-IFNα.

在第二部分（队列4），之前在前瞻性研究（BRII-179-835-001）中接受过9剂elebsiran和BRII-179治疗的参与者根据他们的峰值乙型肝炎表面抗体（anti-HBs）水平（≥10 IU l-1或<10 IU l-1）被分类为BRII-179 anti-HBs反应者或非反应者，随后接受了13剂每4周一次的100 mg elebsiran治疗加上48周的PEG-IFNα每周剂量。

Primary endpoints were HBsAg loss at the end of treatment (EOT) and 24 weeks post-EOT.

主要终点是治疗结束时（EOT）和EOT后24周的HBsAg丧失。

In part I, at 24 weeks post-EOT, HBsAg loss was observed in 4 out of 19 (21.1%) participants receiving elebsiran 200 mg plus PEG-IFNα, 6 out of 18 (33.3%) participants receiving elebsiran 100 mg plus PEG-IFNα and 1 out of 18 (5.6%) participants receiving PEG-IFNα monotherapy.

在第一部分研究中，停药后24周，接受200毫克Elebsiran联合PEG-IFNα治疗的19名参与者中有4名（21.1%）出现HBsAg清除，接受100毫克Elebsiran联合PEG-IFNα治疗的18名参与者中有6名（33.3%）出现HBsAg清除，而仅接受PEG-IFNα单药治疗的18名参与者中有1名（5.6%）出现HBsAg清除。

In part II, HBsAg loss was observed in 9 out of 31 (29.0%) participants at 24 weeks post-EOT, with a higher response among BRII-179 anti-HBs responders (8 out of 19 participants, 42.1%) compared with nonresponders (1 out of 12 participants, 8.3%).

在第二部分研究中，停药后24周，31名参与者中有9名（29.0%）出现HBsAg清除，其中BRII-179抗HBs应答者（19名参与者中有8名，42.1%）的应答率高于非应答者（12名参与者中有1名，8.3%）。

Elebsiran and PEG-IFNα combination therapy was generally safe and well tolerated.

Elebsiran和PEG-IFNα联合疗法总体上是安全且耐受性良好的。

These results demonstrate an additive benefit of elebsiran when combined with PEG-IFNα in achieving sustained HBsAg loss.

这些结果表明，当Elebsiran与PEG-IFNα联合使用时，可实现持续HBsAg丧失的附加益处。

Furthermore, the increased HBsAg loss rate in BRII-179 anti-HBs responders suggests that BRII-179 may be a valuable tool for immunological profiling to optimize curative outcomes in patients with HBV infection.

此外，BRII-179抗HBs应答者中HBsAg丧失率的增加表明，BRII-179可能是用于免疫学分型以优化乙型肝炎病毒感染患者治愈结果的宝贵工具。

ClinicalTrials.gov registration: NCT05970289 .

ClinicalTrials.gov注册号：NCT05970289。