A Single and Repeated Dose Escalation, Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics and Preliminary Pharmacodynamics of RBD1016 in Subjects with Chronic Hepatitis B Virus (HBV) Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, single (Part A) and repeated dose (Part B) escalation, phase I clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary pharmacodynamics (PD) of RBD1016 in subjects with chronic HBV infection.
详细描述
The study consists of two parts. Part A is the single dose escalation study where subjects with chronic HBV infection will be assigned to receive single dose of RBD1016 or placebo . Part B is the multiple dose escalation study where subjects with chronic HBV infection will be assigned to receive two doses of RBD1016 or placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who voluntarily participate in this clinical trial, are able to correctly understand and have signed the informed consent in writing;
- •Male or female volunteer aged 18-55 years (inclusive);
- •Body Mass Index (BMI) of 18-30 kg/m2 (inclusive);
- •Subjects with chronic HBV infection, including immunotolerant subjects, treatment naïve subjects and treated subjects.
- •Ability to cooperate with study staff and comply with the study requirements and follow the protocol-specified procedures.
排除标准
- •Subjects with liver diseases other than hepatitis B, including hepatitis C, hemochromatosis, primary sclerosing cholangitis; alcoholic, drug-related or autoimmune liver diseases; primary liver cancer and indeterminate nodules on liver imaging test;
- •A history or manifestations of liver decompensation (e.g. Child-Pugh Class B or C, or ascites, gastrointestinal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis, etc.);
- •Transient elastography at screening revealing FibroScan value ≥ 9 kPa or liver biopsy evidencing hepatic fibrosis within 24 months;
- •The following laboratory findings: total serum bilirubin> 2×ULN; serum alpha-fetoprotein>50μg/L; serum albumin <3.5g/dL; international normalized ratio (INR)> 1.25; serum creatinine > 1.5×ULN; any laboratory outliers of clinical significance that in the investigator's opinion may interfere with the interpretation of efficacy or safety data;
- •12-lead ECG abnormalities with clinical significance;
- •Pregnant or lactating women or women of child-bearing potential who are unwilling to take effective contraception throughout the course of the study (refer to Appendix 3 for details);
- •Other factors that in the investigator's opinion would make it inappropriate for the subject to participate in the study.
研究组 & 干预措施
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
干预措施: Placebo (Drug)
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
干预措施: RBD1016 (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
干预措施: RBD1016 (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
干预措施: Placebo (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
干预措施: Entecavir (Drug)
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
干预措施: Entecavir (Drug)
结局指标
主要结局
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
时间窗: up to 28 days
All reported AE terms will be coded using Medical Dictionary for Drug Regulatory Affairs (MedDRA).AEs and SAEs occurred throughout the course of the study will be evaluated and graded based on NCI-CTCAE V5.0.
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)
时间窗: up to 28 days
All reported AE terms will be coded using Medical Dictionary for Drug Regulatory Affairs (MedDRA).AEs and SAEs occurred throughout the course of the study will be evaluated and graded based on NCI-CTCAE V5.0.
次要结局
- To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-inf (Part A).(up to 85 days)
- To characterize the pharmacokinetic parameter Vd (Part A).(up to 85 days)
- To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter t1/2 (Part B).(up to 113 days)
- To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Tmax (Part A).(up to 85 days)
- To characterize the pharmacokinetic parameter CL/F (Part A)(up to 85 days)
- To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Tmax (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter AUC0-inf (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter Vd (Part B).(up to 113 days)
- To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter t1/2 (Part A).(up to 85 days)
- To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-t (Part A).(up to 85 days)
- To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of B cell dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Cmax (Part A).(up to 85 days)
- To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of B cell dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-t (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter CL/F (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter Cmax (Part B).(up to 113 days)