A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 in Patients With Chronic Hepatitis B.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This study is a Multiple Ascending Dose study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of APG-1387 in Chronic Hepatitis B Patients.
详细描述
APG-1387 is a potent, bivalent small-molecule IAP antagonist. This study is multi-center, single-agent, open-label, Phase I dose-escalation study of APG-1387.
This study has a 4-dose-schedule which is escalated one by one after confirming safety in the previous lower dose schedule. A total of 60 subjects with Chronic Hepatitis B will be participated in the study. APG-1387 will be administrated via intravenous infusion, once a week for consecutive 4 weeks as one cycle.The start dose is 7mg. 3 patients' cohorts will be evaluated, the dose of APG-1387 will be increased in subsequent cohorts, to 12mg, 20 mg, 30 mg, 45 mg accordingly. 3 patients in 7mg,12mg cohorts and 6 patients in 20mg, 30mg and 45mg cohorts will be recruited. If there is any one of the following event is observed within 28 days of the first dose of APG-1387, the recruitment will be hold and a discussion on MTD dose level will happened.1 ≥1/2 patients experience ≥Grade 2 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387 and with clinical manifestation. 2 ≥1/3 patients experience ≥Grade 3 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387.3 any SAE related or possibly related with APG-1387. Expansion study will be designed to explore primary efficacy and safety after the dose escalation study. The expansion number and dosage will be decided according to the results of each cohort.(no more than 36 patients).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
APG-1387 for Injection
APG-1387 will be explored sequentially using a escalation scheme at the dose escalation phase.
干预措施: APG-1387 for Injection (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 28 days
Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0.3
次要结局
- Pharmacokinetic evaluation(28 days)
- Change in serum HBcAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)
- Change in serum HBeAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)
- Change in serum HBV DNA from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)
- Change in serum HBsAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)
- Change in serum HBeAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)
- Change in serum HBsAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.(Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112)