A Randomized, Open-label, Controlled, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine 600 mg and Tenofovir Disproxil Fumarate 300 mg in Combination or Telbivudine 600 mg or Tenofovir Disproxil Fumarate 300 mg Monotherapy Given Over 12 Weeks on the Kinetics of Hepatitis B Virus DNA in Adults With HBeAg Positive Compensated CHB
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
研究概览
简要总结
The purpose of this study is to compare the safety, tolerability and effectiveness of 12 weeks of treatment with telbivudine 600 mg daily plus tenofovir DF 300 mg one daily (OD) taken together vs. tenofovir DF 300 mg once daily (QD) or vs telbivudine 600 mg monotherapy daily (QD). This is an open labeled, active controlled, viral kinetics study which means the subjects and study doctor will know what study drug subjects have been assigned. This study is open to male and female subjects, <40 years of age, who have been infected with HBV for at least 6 months and have not received oral treatment for HBV.
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
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive > 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc
- •Age < 40 years old
- •HBeAg positive
- •HBV DNA > or = to 10^7 copies/mL by Abbott real-time PCR
- •ALT < or = to 1 ULN
- •Willing and able to provide written informed consent
- •No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
- •Is willing and able to comply with the study drug regimen and all other study procedures and requirements
- •Is willing and able to provide written informed consent before any study assessment is perform
排除标准
- •Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
- •Received interferon (pegylated or not) therapy within 6 months of the screening visit
- •α-fetoprotein > 50 ng/mL
- •Evidence of hepatocellular carcinoma (HCC)
- •Co-infection with HCV (by serology), or HIV,
- •Significant renal, cardiovascular, pulmonary, or neurological disease.
- •Received solid organ or bone marrow transplantation.
- •Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
- •Has proximal tubulopathy.
- •Use of other investigational drugs at the time of enrollment, or within 30 days
- •History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- •Is pregnant or breastfeeding.
- •Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
- •Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.
- •Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
- •Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Telbivudine 600 mg monotherapy
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
干预措施: Telbivudine (Drug)
Tenofovir disproxil fumarate 300 mg monotherapy
All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
干预措施: Tenofovir (Drug)
Telbivudine 600 mg and Tenofovir 300 mg
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
干预措施: Telbivudine plus tenofovir (Drug)
结局指标
主要结局
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
时间窗: Baseline, Week 12
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
次要结局
- Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.(Baseline, Week 2, Week 4, Week 8)
- Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12(Week 12)
- Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12(Week 12)
- Characterization of Very Early Viral Kinetics Through Estimated Viral Load(Week 12)
- Characterization of Very Early Viral Kinetics Through Viral Clearance(Week 12)
- Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss(Week 12)
- Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.(Week 12)
- Characterization of Very Early Viral Kinetics Through Half-live of Free Virus(Week 12)