A PhaseII, Open-Label, Multinational, Multi-Centre, Sequential Group, Dose-Escalation Study to Assess the Safety and Antiviral Activity of LB80380 for 12 Weeks in Patients With Lamivudine-Refractory Chronic Hepatitis B
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 4
- 主要终点
- Mean serum HBV DNA level (log10) reduction from the baseline at Week 12
研究概览
简要总结
The purpose of the study is to investigate the safety and the antiviral activity of ascending multiple oral doses of LB80380 for 12 weeks in adults with lamivudine-refractory chronic hepatitis B infection.
详细描述
LB80380, an oral prodrug, is a promising candidate nucleoside analogue with antiviral activity against wild-type HBV. LB80380 is undergoing clinical development by LG Life Sciences for use in the treatment of chronic HBV infection and for treatment of lamivudine-resistant disease.
In this study, the treatment period was divided into two parts: a 4-week treatment period with dose escalation assessment (Part 1), followed by an 8-week extension period (Part 2).
During Part 1, patients received LB80380 and LVD 100 mg once daily for 4 weeks. Each patient was then given only LB80380 for an additional 8 weeks (Part 2) unless dose-limiting toxicity (DLT) was observed during Part 1. At each dose level, all patients were to complete at least Part 1 of the treatment period before enrolment into the next Dose Group could commence. Dose escalation to the next group was not to be initiated if more than two patients experienced DLT during Part 1 in the previous Dose Group. Additionally, patients enrolled in LB80380 150mg and 240mg groups who agreed to participate in the pharmacokinetic (PK) analyses visited the study site the day before Week 12 for blood sampling. Follow-up period was 24 weeks, and patients were treated with adefovir dipivoxil during the follow-up period. During the study, patients were evaluated for changes from baseline in serum HBV DNA. Safety was evaluated on the basis of occurrence of AEs and changes from baseline in clinical laboratory parameters, physical examination findings, and vital signs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Compensated chronic hepatitis B patient
- •Presence of serum HBsAg for more than 6 months.
- •Presence of HBeAg for more than 1 month with compensated liver disease
- •Confirmation of YMDD mutants (M552V, M552I and its related double mutant at L528M) by genotyping of the YMDD motif using line probe assay (INNO-LiPA HBV DR assay)
- •Screening HBV DNA value higher than or equal to 1,000,000 copies/mL (measured by the COBAS Amplicor HBV Monitor™ assay)
- •Screening ALT value between 1.5 and 10 x ULN
排除标准
- •Co-infection with hepatitis C or D virus (HCV or HDV) or HIV
- •Pregnancy or breast-feeding
- •Previous treatment with nucleoside analogue or any other treatment for HBV except for lamivudine within 6 months prior to study entry
- •Treatment with immunomodulatory agent or corticosteroids within 6 months prior to study entry.
- •De-compensated liver disease
- •Screening alpha-fetoprotein (AFP) value > 20 ng/mL, and a follow-up ultrasonography performed prior to baseline shows findings indicative of HCC.
- •Presence of anti-HBs at screening
研究组 & 干预措施
LB80380 30mg
LB80380 30mg
干预措施: LB80380 (Drug)
LB80380 60mg
LB80380 60mg
干预措施: LB80380 (Drug)
LB80380 90mg,
LB80380 90mg
干预措施: LB80380 (Drug)
LB80380 150mg
LB80380 150mg
干预措施: LB80380 (Drug)
LB80380 240mg
LB80380 240mg
干预措施: LB80380 (Drug)
结局指标
主要结局
Mean serum HBV DNA level (log10) reduction from the baseline at Week 12
时间窗: Week 12
次要结局
- Proportion of patients with HBeAg seroconversion at 12 weeks Proportion of patients with HBsAg seroconversion at 12 weeks Proportion of patients with ALT normalization at 12 weeks Safety assessment during the whole study period(Week 12)