A randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally suppressed patients with chronic hepatitis B who are HBeAg-negative.

ASC22 (envafolimab) is a humanized, single-domain programmed cell death ligand 1 antibody administered subcutaneously.

ASC22（envafolimab）是一种人源化单域程序性细胞死亡配体1抗体，通过皮下注射方式给药。

This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs.

本研究旨在评估ASC22在使用核苷(酸)类似物治疗的慢性乙型肝炎病毒抑制患者中的疗效和安全性。

approach_and_results

This randomized, single-blind, phase IIb trial enrolled patients with chronic hepatitis B in 2 cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up.

这项随机、单盲、IIb期试验招募了两组慢性乙型肝炎患者，分别接受每两周一次的ASC22或安慰剂（PBO）治疗，持续24周，并进行24周的随访。

In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22, and PBO, respectively.

总共，分别有60名、59名和30名患者接受了1.0 mg/kg ASC22、2.5 mg/kg ASC22和安慰剂治疗。

The mean changes in HBsAg from baseline at weeks 24 and 48 were -0.309 ( p < 0.001) and -0.272 ( p < 0.023) log 10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 ( p = 0.007) and -0.205 ( p = 0.12) log 10 IU/mL in the 2.5 mg/kg ASC22 group, and -0.003 and -0.063 log 10 IU/mL in the PBO group, respectively (intent-to-treat population).

在基线时，分别在第24周和第48周，1.0 mg/kg ASC22组的HBsAg平均变化为-0.309 (p < 0.001)和-0.272 (p < 0.023) log 10 IU/mL，2.5 mg/kg ASC22组的平均变化为-0.231 (p = 0.007)和-0.205 (p = 0.12) log 10 IU/mL，而安慰剂组的平均变化为-0.003和-0.063 log 10 IU/mL（意向治疗人群）。

Three out of 10 patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss.

1.0 mg/kg组中，基线HBsAg水平≤100 IU/mL的患者有30%在治疗期间获得了HBsAg清除。

Most adverse events were mild (97.9%).

大多数不良事件为轻度（97.9%）。

There were no study drug-related serious adverse events in the 1.0 mg/kg ASC22 group.

在1.0 mg/kg ASC22组中，未发现与研究药物相关的严重不良事件。

Conclusions

Subcutaneous administration of 1.0 mg/kg ASC22 once every 2 weeks for 24 weeks was shown to be safe and well-tolerated in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.

每两周皮下注射1.0 mg/kg ASC22，连续24周，对于使用核苷（酸）类似物治疗的慢性乙型肝炎病毒抑制患者是安全且耐受性良好的，并且可以诱导HBsAg下降，尤其在HBsAg ≤100 IU/mL的患者中。