A Phase 2, Randomized, Double-Blind Study Exploring the Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects Currently Being Treated With Adefovir Dipivoxil for Chronic Hepatitis B and Having Persistent Viral Replication
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 106
- 主要终点
- Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48
研究概览
简要总结
This study explores the efficacy, safety and tolerability of tenofovir DF (TDF) 300 mg once daily monotherapy versus the combination of emtricitabine 200 mg plus tenofovir DF 300 mg (FTC/TDF) once daily in subjects currently being treated with adefovir dipivoxil (Hepsera) for chronic hepatitis B who have persistent viral replication (detectable hepatitis B virus deoxyribonucleic acid [HBV DNA]).
Subjects with confirmed (within 4 weeks) plasma HBV DNA ≥ 400 copies/mL during double blind treatment at Week 24 or any time thereafter have the option of receiving 12 weeks of open-label FTC/TDF which may be continued through the end of the 168-week treatment period if there is a virologic response (HBV DNA < 400 copies/mL). Alternatively, subjects with confirmed HBV DNA < 400 copies/mL at or any time after Week 24 of double-blind treatment may continue blinded therapy up to Week 168 at the discretion of the investigator. If, in the investigator's opinion, it is felt that continued blinded treatment beyond 24 weeks in subjects with confirmed HBV DNA ≥ 400 copies/mL is not beneficial, the subject may discontinue the study and begin commercially available HBV therapy rather than initiate open-label FTC/TDF.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 through 69 years of age, inclusive
- •Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
- •Active chronic HBV infection with all the following:
- •Currently treated with adefovir dipivoxil 10 mg QD (for at least 24 weeks but not more than 96 weeks)
- •HBeAg positive or negative at screening
- •Plasma HBV DNA >/= 1000 copies/mL at screening (irrespective of HBeAg status)
- •Serum ALT less than 10 times the upper limit of normal (ULN)
- •Calculated creatinine clearance of at least 70 mL/min using the Cockcroft-Gault formula
- •Hemoglobin at least 8 g/dL
- •Neutrophils at least 1,000 /mm3
- •Nucleoside naive except for lamivudine (>/= 12 weeks of therapy)
- •Negative serum beta human chorionic gonadotropin
- •Compliant with adefovir dipivoxil
- •Willing and able to provide written informed consent
排除标准
- •Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
- •Male or females of reproductive potential who are unwilling to use an effective method of contraceptive while enrolled in the study. For males, condoms should be used and for females, a barrier contraception method should be used
- •Decompensated liver disease defined as conjugated bilirubin greater than 1.5 times ULN, prothrombin time (PT) greater than 1.5 times ULN, platelets less than 75,000/mm3, serum albumin less than 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)
- •Prior use of tenofovir DF or entecavir
- •Received treatment with interferon or pegylated interferon within 6 months of the screening visit
- •Evidence of hepatocellular carcinoma (HCC); for example, alpha-fetoprotein greater than 50 ng/mL or by any other standard of care measure.
- •Co-infection with HCV (based on serology), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV)
- •Significant renal, cardiovascular, pulmonary, or neurological disease.
- •Received solid organ or bone marrow transplantation.
- •Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
- •Has proximal tubulopathy
- •Known hypersensitivity to the study drugs (tenofovir DF or emtricitabine/tenofovir DF), the metabolites (tenofovir or emtricitabine) or formulation excipients
研究组 & 干预措施
1
TDF
干预措施: tenofovir DF (Drug)
2
FTC/TDF
干预措施: emtricitabine /tenofovir DF (Drug)
结局指标
主要结局
Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48
时间窗: 48 weeks
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
时间窗: 48 Weeks
次要结局
- Change From Baseline in log10 Plasma HBV DNA Levels at Week 48(48 Weeks)
- Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48(48 Weeks)
- Percentage of Participants With Normal ALT at Week 48(48 Weeks)
- Percentage of Participants With Normalized ALT at Week 48(48 Weeks)
- Hepatitis B Early Antigen (HBeAg) Loss at Week 48(48 Weeks)
- HBeAg Seroconversion at Week 48(48 Weeks)
- HBsAg Loss at Week 48(48 Weeks)
- Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48(48 Weeks)
- Change From Baseline in log10 Plasma HBV DNA Levels at Week 168(168 weeks)
- Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168(168 weeks)
- Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168(168 weeks)
- Percentage of Participants With Normal ALT at Week 168(168 weeks)
- Percentage of Participants With Normalized ALT at Week 168(168 weeks)
- Hepatitis B Early Antigen (HBeAg) Loss at Week 168(168 weeks)
- Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168(168 weeks)
- HBsAg Loss at Week 168(168 weeks)
- Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168(168 weeks)