Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.
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Hou Jinlin, Zhang Wenhong, Xie Qing, Hua Rui, Tang Hong, Morano Amado Luis Enrique, Yang Sheng-Shun, Peng Cheng-Yuan, Su Wei-Wen, Chuang Wan-Long, Kim Dong Joon, Avihingsanon Anchalee, Kao Jia-Horng, Leerapun Apinya, Yuen Man-Fung, Asselah Tarik, Liang Xieer, Bo Qingyan, Canducci Filippo, Catanese Maria Teresa, Chen Ethan, Cheng Cong, Chughlay Farouk, Das Sudip, Glavini Katerina, Guerreiro Nelson, Huang Yan, Kakrana Priyanka, Kazma Rémi, Patil Avinash, Pavlovic Vedran, Surujbally Bernadette, Triyatni Miriam, Upmanyu Ruchi, Wat Cynthia, Gane Edward, Piranga Study Group
Аннотация
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 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.
CONCLUSIONS: 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.).