Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B

作者：Jinlin Hou, Wenhong Zhang, Qing Xie, Rui Hua, Hong Tang, Luís Morano, Sheng‐Shun Yang, Cheng‐Yuan Peng, Wei‐Wen Su, Wan‐Long Chuang, Dong Joon Kim, Anchalee Avihingsanon, Jia‐Horng Kao, Apinya Leerapun, Man-Fung Yuen, Tarik Asselah, Xieer Liang, Qingyan Bo, Filippo Canducci, Maria Teresa Catanese, Ethan Chen, Cong Cheng, Farouk Chughlay, Sudip Das, Katerina Glavini, Nelson Guerreiro, Yan Huang, Priyanka Kakrana, Rémi Kazma, Avinash S. Patil, Vedran Pavlovic, Bernadette Surujbally, Miriam Triyatni, Ruchi Upmanyu, Cynthia Wat, Edward Gane · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2405485 · 被引用次数：77 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、RNA Interference and Gene Delivery

BACKGROUND: 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. METHODS: 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. RESULTS: 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...