Phase IIa Single Dose and Phase IIb Mutiple Dose Clinical Studies to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Subcutaneously Injected PD-L1 Antibody ASC22 in Patients With Chronic Hepatitis B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 1
- 主要终点
- Evaluate the decreased HBsAg levels at 12 or 24 weeks of treatment or at 4, 12, or 24 weeks of follow-up visits compared with baseline.
研究概览
简要总结
The objective of this study is to evaluate the safety and efficacy of ASC22 in the treatment of chronic hepatitis B after single and multiple drug administration.
详细描述
The study consists of two parts: the ASC22 single-dose IIa study and the ASC22 multi-dose IIb study. The IIa study consists of 3 cohorts of 0.3mg/kg, 1.0mg/kg and 2.5mg/kg, and the IIb study consists of 2 cohorts of 1.0mg/kg and 2.5mg/kg. The objective is to evaluate the safety, tolerance and efficacy of ASC22 in patients with chronic hepatitis B (CHB), and to provide a guidance for the determination of dosage regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years old (including boundary value), gender unlimited；
- •Chronic hepatitis B patients with clear diagnosis of Hematology, etiology and clinical (for example: HBsAg positive for more than 6 months);
- •HBV-DNA turns negative after treatment with nucleoside (acid) drugs;
- •cohort1-5:HBsAg≤ 10000 IU/mL; cohort6: HBsAg≤ 100 IU/mL;
- •HBeAg negative;
- •The fertile female subjects or the fertile male subjects agreed to take contraceptive measures from 7 days before the first administration until 24 weeks after the end of the administration cycle of ASC
- •The serum pregnancy test of fertile female subjects must be negative within 7 days before the first administration.
排除标准
- •Patients with hepatitis a, hepatitis c (HCV RNA>15IU/L), hepatitis d or HIV infection; Patients with other active infections (e.g., respiratory tract infection, urinary tract infection and herpes simplex, cytomegalovirus, epstein-barr virus);
- •Fibrosis stage: Cirrhosis, portal hypertension, or advanced fibrosis (defined as Fibroscan≥9.5kPa or ARFI≥1.81m/sec or Fibrosis-4 (FIB-4)≥3.25 or METAVIR F≥3);
- •Liver cancer patients or blood AFP>1×ULN;
- •cohort1-5：Patients who received interferon therapy within 6 months before the first administration; cohort6: Patients who received interferon therapy before the first administration;
- •Patients receiving immunosuppressive therapy within 3 months before the first administration (except interferon);
- •The investigator judges that the participants are not suitable for this study.
研究组 & 干预措施
cohort3:Single dose ASC22 injection 2.5mg/kg
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.
干预措施: ASC22 (Drug)
cohort1: Single dose ASC22 injection 0.3mg/kg
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.
干预措施: ASC22 (Drug)
cohort2:Single dose ASC22 injection 1.0mg/kg
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.
干预措施: ASC22 (Drug)
cohort4: Multiple dose ASC22 injection 1.0mg/kg
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
干预措施: ASC22 (Drug)
cohort5: Multiple dose ASC22 injection 2.5mg/kg
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks
干预措施: ASC22 (Drug)
cohort4: Placebo sodium chloride injection A
Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).
干预措施: sodium chloride (Drug)
cohort5: Placebo sodium chloride injection B
Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (2.5mg/kg).
干预措施: sodium chloride (Drug)
cohort6: Multiple dose ASC22 injection 1.0mg/kg
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
干预措施: ASC22 (Drug)
cohort6: Placebo sodium chloride injection A
Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).
干预措施: sodium chloride (Drug)
结局指标
主要结局
Evaluate the decreased HBsAg levels at 12 or 24 weeks of treatment or at 4, 12, or 24 weeks of follow-up visits compared with baseline.
时间窗: 48 weeks
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Evaluate the number of patients with ≥0.5log reduction in HBsAg log10IU/ mL at 12 or 24 weeks of treatment, or at 4, 12, or 24 weeks of follow-up visits compared with baseline.
时间窗: 48 weeks
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
次要结局
- Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort.(48 weeks)
- Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort.(48 weeks)
- Evaluate the decline value of HBsAg level.(48 weeks)
- Evaluate the changes of peripheral blood lymphocyte subsets in each cohort.(48 weeks)