A Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 280
- 主要终点
- Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
研究概览
简要总结
The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. The clinical guidelines for the management of lamivudine resistant patients are variable. Some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. Limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen.
This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or without the rtL180M mutation) over a 240-week period. Participants in this study must be receiving lamivudine treatment at the time of enrollment.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 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
Tenofovir DF
TDF plus placebo to match FTC/TDF
干预措施: TDF (Drug)
Tenofovir DF
TDF plus placebo to match FTC/TDF
干预措施: FTC/TDF Placebo (Drug)
FTC/TDF
FTC/TDF plus placebo to match TDF
干预措施: FTC/TDF (Drug)
FTC/TDF
FTC/TDF plus placebo to match TDF
干预措施: TDF Placebo (Drug)
结局指标
主要结局
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
时间窗: Week 96
次要结局
- Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240(Baseline; Weeks 48, 96, 144, 192, and 240)
- Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240(Weeks 48, 144, 192, and 240)
- Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240(Baseline; Weeks 48, 96, 144, 192, and 240)
- Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240(Baseline; Weeks 48, 96, 144, 192, and 240)
- Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240(Baseline; Weeks 48, 96, 144, 192, and 240)
- Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240(Baseline; Weeks 48, 96, 144, 192, and 240)
- Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240(Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240)
- Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240(Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240)
- Development of Drug-resistant Mutations (DRMs)(Baseline to Week 240)
- Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240(Weeks 48, 96, 144, 192, and 240)
- HBV DNA Level at Weeks 48, 96, 144, 192, and 240(Weeks 48, 96, 144, 192, and 240)
- Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240(Weeks 48, 96, 144, 192, and 240)