Hepatology international · 2026
Safety, pharmacokinetics and antiviral activity of AHB‑137 in healthy volunteers and chronic hepatitis B patients: a phase 1a/1b study.
Клиническое исследование I фазыКлиническое исследование II фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Wen, Mai Jiajia, Hou Jinlin, Xu Zhongyuan, Yu Xian, Ren Hong, Liang Xieer, Yang Yi, Liu Zhihong, Zhang Hong, Zhong Shan, Wen Yilei, Lu Tingting, Cao Haixia, Qiu Xiao, Wang Lidan, Zhao Di, Wang Miao, Yang Chengyong, Cheng Guofeng, Niu Junqi, Ding Yanhua
Аннотация
BACKGROUND/PURPOSE: AHB-137 is a novel antisense oligonucleotide targeting a conserved 3'-terminal region of HBV mRNA. This phase 1a/1b study evaluated the safety, pharmacokinetics (PK), and antiviral activity of AHB-137 in Chinese healthy volunteers (HVs) and chronic hepatitis B (CHB) patients.
METHODS: In Phase 1a, 52 HVs received single ascending doses (75-450 mg) or multiple ascending doses (MAD; 150 or 300 mg) of AHB-137 or placebo. In Phase 1b, 20 HBeAg-negative, nucleos(t)ide analogue (NA)-suppressed CHB patients with baseline HBsAg 100-1000 IU/mL received MAD AHB-137 (150 or 300 mg) or placebo (8:2), and 2 patients with baseline HBsAg 1000-3000 IU/mL received open-label AHB-137 300 mg. MAD comprised 6 subcutaneous doses over 4 weeks including loading doses on Days 4 and 11, with safety, PK and virologic follow-up assessments.
RESULTS: No serious adverse events, deaths or discontinuations occurred. Most treatment-related adverse events were Grade 1-2, including injection site reactions, pyrexia, and asymptomatic lab abnormalities. Transaminase elevations were self-limiting; one Grade 3 ALT elevation in the 300 mg CHB cohort coincided with rapid HBsAg loss. PK showed rapid absorption (Tmax 3-5 h), dose-proportionality, and a terminal half-life of 128-195 h without meaningful accumulation. In CHB patients, 4 weeks of AHB-137 induced dose-dependent HBsAg reductions (mean maximum - 1.1 vs. - 2.1 log10 IU/mL at 150 vs. 300 mg), 50.0% of the 300 mg cohort achieved ≥ 2 log10 IU/mL reduction. Preliminary HBsAg loss was observed in a small subset of patients during follow-up.
CONCLUSION: AHB-137 demonstrated favorable safety, predictable PK, and dose-dependent HBsAg reductions, including HBsAg loss, supporting its further development for CHB functional cure.
REGISTRATION NUMBER: ClinicalTrials.gov. number: NCT06115993. Chinadrugtrials.org.cn. number: CTR20232098.
METHODS: In Phase 1a, 52 HVs received single ascending doses (75-450 mg) or multiple ascending doses (MAD; 150 or 300 mg) of AHB-137 or placebo. In Phase 1b, 20 HBeAg-negative, nucleos(t)ide analogue (NA)-suppressed CHB patients with baseline HBsAg 100-1000 IU/mL received MAD AHB-137 (150 or 300 mg) or placebo (8:2), and 2 patients with baseline HBsAg 1000-3000 IU/mL received open-label AHB-137 300 mg. MAD comprised 6 subcutaneous doses over 4 weeks including loading doses on Days 4 and 11, with safety, PK and virologic follow-up assessments.
RESULTS: No serious adverse events, deaths or discontinuations occurred. Most treatment-related adverse events were Grade 1-2, including injection site reactions, pyrexia, and asymptomatic lab abnormalities. Transaminase elevations were self-limiting; one Grade 3 ALT elevation in the 300 mg CHB cohort coincided with rapid HBsAg loss. PK showed rapid absorption (Tmax 3-5 h), dose-proportionality, and a terminal half-life of 128-195 h without meaningful accumulation. In CHB patients, 4 weeks of AHB-137 induced dose-dependent HBsAg reductions (mean maximum - 1.1 vs. - 2.1 log10 IU/mL at 150 vs. 300 mg), 50.0% of the 300 mg cohort achieved ≥ 2 log10 IU/mL reduction. Preliminary HBsAg loss was observed in a small subset of patients during follow-up.
CONCLUSION: AHB-137 demonstrated favorable safety, predictable PK, and dose-dependent HBsAg reductions, including HBsAg loss, supporting its further development for CHB functional cure.
REGISTRATION NUMBER: ClinicalTrials.gov. number: NCT06115993. Chinadrugtrials.org.cn. number: CTR20232098.