Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment
2014年11月25日 更新者：Bristol-Myers Squibb
A Study of the Safety and Efficacy of Entecavir Plus Tenofovir in Adults With Chronic Hepatitis B Virus Infection With Previous Nucleoside/Nucleotide Treatment Failure
The purpose of this study is to show that the combination of entecavir and tenofovir, is effective and well tolerated in chronic hepatitis B patients who have failed previous treatment.
研究概览
研究类型
介入性
注册 (实际的)
144
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Berlin、德国、13353
- Local Institution
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Berlin、德国、10969
- Local Institution
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Hamburg、德国、20246
- Local Institution
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Hamburg、德国、20099
- Local Institution
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Hannover、德国、30625
- Local Institution
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Heindelberg、德国、69120
- Local Institution
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Munchen、德国、81675
- Local Institution
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Tubingen、德国、72076
- Local Institution
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Bagno A Ripoli (Fi)、意大利、50012
- Local Institution
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Bari、意大利、70124
- Local Institution
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Foggia、意大利、71100
- Local Institution
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Milano、意大利、20122
- Local Institution
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Clichy、法国、92110
- Local Institution
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Lyons Cedex 04、法国、69317
- Local Institution
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Orleans Cedex 2、法国、45067
- Local Institution
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Strasbourg、法国、67000
- Local Institution
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Kielce、波兰、25-317
- Local Institution
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Krakow、波兰、31-531
- Local Institution
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Lodz、波兰、91-347
- Local Institution
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Wroclaw、波兰、50-349
- Local Institution
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Bucuresti、罗马尼亚、021105
- Local Institution
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Burcuresti、罗马尼亚、022328
- Local Institution
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Timisoara、罗马尼亚、300 002
- Local Institution
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Amsterdam、荷兰、1105 AZ
- Local Institution
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Arnhem、荷兰、6815 AD
- Local Institution
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Rotterdam、荷兰、3015 CE
- Local Institution
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Barcelona、西班牙、08025
- Local Institution
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Valencia、西班牙、46014
- Local Institution
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Subjects with chronic hepatitis B virus (HBV) infection; either hepatitis B-e antigen(HBeAg)-negative or HBeAg-positive
- Subjects must have a treatment failure to their current nucleoside/ nucleotide treatment regimen
- Prior entecavir and/or tenofovir monotherapy is allowed
- Subjects must have compensated liver function
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- Evidence of decompensated cirrhosis
- Co-infection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
- Moderate or severe renal impairment
- Recent history of pancreatitis
- Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of being assigned to study drug into this study
- Prior entecavir/tenofovir combination therapy
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Entecavir + Tenofovir
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Tablets, Oral, 1 mg, once daily, 96 weeks
其他名称：
Tablets, Oral, 300 mg, once daily, 96 weeks
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants With a Virologic Response at Week 48 - Treated Population
大体时间：Week 48
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 48
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
大体时间：Week 24, Week 96
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 24, Week 96
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Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
大体时间：Baseline to Weeks 12, 24, 48, 96
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HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Baseline was Day 1, prior to study drug administration.
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Baseline to Weeks 12, 24, 48, 96
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Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
大体时间：Weeks 24, 48, 96
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HBV DNA less than (<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96.
Percentage was calculated as number of participants with HBV DNA < LLD at Weeks 24, 48, 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
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Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
大体时间：Baseline to Weeks 24, 48, and 96
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Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline to Weeks 24, 48, and 96
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Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
大体时间：Baseline, Weeks 24, 48, and 96
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HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
大体时间：Baseline, Weeks 24, 48, 96
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Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline.
The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized).
Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg).
Treated participants (HBsAg-positive at baseline) were evaluated using NC=F.
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
大体时间：Baseline, Weeks 24, 48, and 96
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HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline.
Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline.
Positive result for HBsAg was one of the inclusion criteria.
Treated participants (HBsAg positive at baseline) were evaluated using NC=F.
The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma [potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized].
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
大体时间：Day 1 to last dose of study drug plus 5 days; up to Week 96
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
On-treatment = on Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
大体时间：Baseline to Weeks 48, 96
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Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough.
Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S).
Primary non-response was defined as < 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
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Baseline to Weeks 48, 96
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Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
大体时间：Day 1 to last dose of study drug plus 5 days; up to Week 96
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Selected criteria presented in each category.
Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (>);greater than, equal to (>=); less than (<).
Creatinine data presented below were confirmed, ie, at least 2 consecutive values.
On-treatment = after Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年5月1日
初级完成 (实际的)
2012年11月1日
研究完成 (实际的)
2014年2月1日
研究注册日期
首次提交
2010年2月3日
首先提交符合 QC 标准的
2010年2月4日
首次发布 (估计)
2010年2月5日
研究记录更新
最后更新发布 (估计)
2014年12月15日
上次提交的符合 QC 标准的更新
2014年11月25日
最后验证
2014年11月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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