The Clinical Efficacy of Tenofovir Alafenamide-switching Therapy in Patients With Chronic Hepatitis B Experiencing Clinical Flare-up After Discontinuation of Nucleos[t]Ide Analogues Therapy
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 260
- 试验地点
- 8
- 主要终点
- Rate of virological remission (HBV DNA <20 IU/mL)
研究概览
简要总结
We will conduct a phase 4, multicenter, open-label trial at 8 academic centers in Taiwan.
Chronic hepatitis B patients receiving oral antiviral therapy (entecavir [ETV], tenofovir disoproxil fumarate [TDF]) for at least 1 year, and fulfil the following nucleos(t)ide analogs discontinuation criteria. After nucleos(t)ide analogs discontinuation, patients had a clinical relapse and retreatment regimen switches to TAF.
The protocol will be approved by Institutional Review Board (IRB) or Research ethic committee (REC) of each site and will be conducted in accordance with the principles of Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice. Each patient provides written informed consent before enrollment.
详细描述
Tenofovir alafenamide (TAF) is a new generation of oral antiviral drugs with similar antiviral activities to tenofovir disoproxil fumarate (TDF) and reduces the adverse effects of nephrotoxicity and bone mineral density reduction. This drug has already been reimbursed by National Health Insurance, and can be used for the treatment of patients with chronic hepatitis B.
This is a single-arm prospective clinical trial to enroll patients who discontinued entecavir (ETV) and tenofovir disoproxil fumarate (TDF) and experienced a clinical hepatitis flare up. They can be retreated with TAF for 48 weeks without postponing a 3-month observation period for alanine aminotransferase (ALT) level. The virological control, ALT level recovery, and changes in liver fibrosis, hepatitis B surface antigen, hepatitis B core-associated antigen, and renal function will be observed during retreatment. In addition, a group of patients with the same characteristics who received retreatment with entecavir or TDF will be collected as a control group for comparison. We believe this study can help us understand the clinical benefits of switching to TAF for retreatment after hepatitis flare in patients to discontinue oral antiviral agents.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A. Switching therapy cohort
- •Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 1 years, and fulfil the following NUCs discontinuation criteria (1)HBeAg-positive patients achieved HBeAg loss, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieved virological remission (HBV DNA <20 IU/mL) for more than 1 year
- •After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
- •The retreatment regimen switches to TAF (within 3.3 months of clinical relapse)
- •B. Historical continuing therapy cohort
- •Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 1 years, and fulfil the following NUCs discontinuation criteria (1) HBeAg-positive patients achieved HBeAg loss, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieved virological remission (HBV DNA <20 IU/mL) for more than 1 year
- •After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
- •The patients continued the original regimen (ETV, TDF) for retreatment (within 3.3 months of clinical relapse)
排除标准
- •Patients who do not fulfill the discontinuation criteria
- •Patients who have HCV, HDV or HIV co-infection
- •Patients who discontinue lamivudine, adefovir, or telbivudine therapy
- •Patients with liver cirrhosis by ultrasonography and clinical diagnosis
研究组 & 干预措施
Switching therapy cohort
single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks
干预措施: Vemlidy (Drug)
Historical continuing therapy cohort
By retrospectively review medical records, The patients continued the original regimen (ETV, TDF) for retreatment (within 3.3 months of clinical relapse)
结局指标
主要结局
Rate of virological remission (HBV DNA <20 IU/mL)
时间窗: 48 weeks
We will calculate the rate of virological remission (HBV DNA \<20 IU/mL) after retreatment
次要结局
- Rate of HBsAg change after retreatment compared with baseline(48 weeks)
- Rate of ALT normalization (ALT < 40 U/L) after retreatment(48 weeks)
- Rate of HBcrAg change after retreatment compared with baseline(48 weeks)
- Rate of M2BPGi level change after retreatment compared with baseline(48 weeks)