Efficacy of Long-term Telbivudine Treatment on Histological Improvements in Patients With Chronic Hepatitis B (EFFORT Further Extension Study)
试验速览
- 阶段
- 4 期
- 入组人数
- 130
- 试验地点
- 20
- 主要终点
- Percentage of patients with histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening in Ishak fibrosis score).
研究概览
简要总结
The purpose of this study is to demonstrate that long-term treatment (up to six years) with telbivudine or telbivudine plus adefovir results in the regression in liver inflammation and fibrosis/cirrhosis.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who completed EFFORT extension study.
- •Patients who had baseline (that is the week 0 of EFFORT study) HBV DNA <9 Log copies/mL and ALT ≥2×ULN.
- •Patients who are willing to participate in the further extension study.
- •Patient is willing and able to comply with the study drug regimen and all other study requirements.
- •Patients must give written informed consent before any assessment is performed.
排除标准
- •Poor compliance judged by investigators
研究组 & 干预措施
Off-treatment
Patients who had stopped treatment during EFFORT extension study could receive 2-year off-treatment follow-up. All the patients in Part I will be followed up at the interval of 12 weeks. For these patients, if they have hepatitis flare during follow-up, they will be re-treated with telbivudine combined with adefovir for the left study period ( the total study period is 2 years) and followed up at the interval of 12 weeks. Hepatitis flare is defined as HBV DNA>4 Log10 copies/mL with either ALT≥5 times upper limit of normal (ULN) or TBIL≥2×ULN，or 2 ≤ALT ≤5 ×ULN (at two consecutive visits at least 2 weeks apart) and total bilirubin (TBIL) <2×ULN.
干预措施: off-treatment follow-up (Other)
On-treatment
Patients with continuous treatment during EFFORT extension study will continue treatment, without off-treatment rule in the further extension study. The treatment strategy is depended on the HBV DNA level of each individual, that is, for patients with negative HBV DNA level (defined as HBV DNA <20 IU/mL) will continue their previous treatment strategy; and for patients with positive HBV DNA level (defined as HBV DNA>=20 IU/mL) will receive the combination therapy of telbivudine and adefovir, irrespective of their previous treatment strategy. All the patients in Part II will be followed up at the interval of 24 weeks until they complete the 2-year on-treatment follow-up. Patients will be conducted liver biopsy at the sixth year of treatment. All the patients with telbivudine monotherapy will be switched to telbivudine plus adefovir once confirmed HBV DNA breakthrough developed.
干预措施: Telbivudine (Drug)
On-treatment
Patients with continuous treatment during EFFORT extension study will continue treatment, without off-treatment rule in the further extension study. The treatment strategy is depended on the HBV DNA level of each individual, that is, for patients with negative HBV DNA level (defined as HBV DNA <20 IU/mL) will continue their previous treatment strategy; and for patients with positive HBV DNA level (defined as HBV DNA>=20 IU/mL) will receive the combination therapy of telbivudine and adefovir, irrespective of their previous treatment strategy. All the patients in Part II will be followed up at the interval of 24 weeks until they complete the 2-year on-treatment follow-up. Patients will be conducted liver biopsy at the sixth year of treatment. All the patients with telbivudine monotherapy will be switched to telbivudine plus adefovir once confirmed HBV DNA breakthrough developed.
干预措施: Adefovir dipivoxil (Drug)
结局指标
主要结局
Percentage of patients with histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening in Ishak fibrosis score).
时间窗: Week 48
次要结局
- Percentage of patients with HBeAg loss or HBeAg seroconversion at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of patients achieving hepatitis B virus (HBV) DNA <300copies/mL at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of patients with HBsAg loss or HBsAg seroconversion at week 48 and 96 in on-treatment group(week 48, week 96)
- The percentage of patients with alanine aminotransferase (ALT) normalization at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of patients with genotypic resistance among the patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group(week 48, week 96)
- Incidence of adverse effect at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of patients with glomerular filtration rate (GFR) shifting to >90 mL/min/1.73 m2 for patients with GFR <90 mL/min/1.73 m2 at baseline of EFFORT study at week 48 and 96 in on-treatment group(week 48, week 96)
- Sustained response rate of durability of HBeAg seroconversion at week 48 and 96 in off-treatment group(week 48, week 96)
- Percentage of patients who re-achieved ALT normalization and HBV DNA <300 copies/mL in the patients retreated who developed hepatitis flare after stopping treatment in off-treatment group(week 96)
- Incidence of abnormal laboratory examination at week 48 and 96 in on-treatment group(week 48, week 96)
- Percentage of hepatitis flare at week 48 and 96 in off-treatment group(week 48, week 96)