A Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HT-101 Injection and/or HT-102 Injection in Patients With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 86
- 试验地点
- 7
- 主要终点
- Clinically significant abnormalities
研究概览
简要总结
This study is A multicenter, open-label, partial multiple-ascending doses phase1b/2 in which participants with chronic hepatitis B virus (HBV) infection will receive HT-101 and/or HT-102 and be assessed for safety, tolerability, Pharmacokinetics, and Pharmacodynamics. Approximately 86 patients with chronic hepatitis B infection were planned to be recruited. Among them, Group A and Group AA received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks. Group B received HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks. Groups C, D, and E received HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks. During the study period, all subjects received nucleoside (acid) analogues (NAs) treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Subjects were eligible for inclusion into the study if they met each of the following criteria:
- •Patient with CHB
- •Male subjects weighed ≥ 50.0 kg, female subjects weighed ≥ 45.0 kg, with a body mass index (BMI) between 19.0 and 28.0 kg/m^2 (inclusive); Chronic HBV infection for >/= 6 months; The quantitation level of HBsAg was > 100 IU/mL and <3000 IU/mL; The quantitation level of HBV DNA <LLOQ;
- •· On Nas therapy for >/= 6 months at the time of screening
- •Subjects promised to use effective contraception for at least 1 month before screening, and have no fertility, donate sperm or eggs and voluntarily take highly effective physical contraception (including partners) during the trial and within 3 months after the end of the trial;
排除标准
- •Subjects were excluded from the study if one or more of the following criteria were applicable
- •Participants with history of drug allergy or specific allergy; Participants who had psychiatric conditions or diseases in cardiovascular, respiratory, endocrine, kidney, liver, digestive tract, skin, immune, blood, nerve and other systems; Participants with history of active pathological bleeding, or bleeding tendency; Participants with abnormal results of physical examination, vital sign examination, ECG examination, laboratory test in the screening period which were judged as clinically significant by clinicians; Participants with significant liver fibrosis or cirrhosis; Participants with symptoms or a history of hepatic decompensation; Participants with a history or suspected risk of liver cancer;
研究组 & 干预措施
Experimental: Cohort D (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-102 (Drug)
Experimental: Cohort A (HT-101)
Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks
干预措施: HT-101 (Drug)
Experimental: Cohort AA (HT-101)
Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks
干预措施: HT-101 (Drug)
Experimental: Cohort B （HT-102；HT-101）
Participants will receive HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks
干预措施: HT-101 (Drug)
Experimental: Cohort B （HT-102；HT-101）
Participants will receive HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks
干预措施: HT-102 (Drug)
Experimental: Cohort C (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-101 (Drug)
Experimental: Cohort C (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-102 (Drug)
Experimental: Cohort D (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-101 (Drug)
Experimental: Cohort E (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-101 (Drug)
Experimental: Cohort E (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
干预措施: HT-102 (Drug)
结局指标
主要结局
Clinically significant abnormalities
时间窗: From enrollment to the end of treatment at up to 60 weeks
Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
Incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: From enrollment to the end of treatment at up to 60 weeks
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
次要结局
- Maximum Change of Serum HBsAg From Baseline(Up to 48 weeks)
- Maximum Change of Serum HBV DNA From Baseline(Up to 48 weeks)
- Titers of Anti-drug Antibody (ADA) to HT-102(UP to 36 weeks)
- Maximum Plasma Concentration (Cmax)(HT-101: From predose 1 hour to postdose 24 hours HT-102：UP to 36 weeks)
- Time to Reach Maximum Plasma Concentration (Tmax)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Area Under the Plasma Concentration Versus Time Curve (AUC)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent Terminal Elimination Half-life (T1/2)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent Plasma Clearance (CL/F)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent volume of distribution（Vd/F）(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)