Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection
2014年1月30日 更新者：Sang Hoon Ahn、Yonsei University
A Multicenter, Open-label, Prospective Study to Evaluate Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection
Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will show effective antiviral activity and prevent further development of antiviral resistance in hepatitis B e antigen(HBeAg)-positive or -negative Chronic Hepatitis B(CHB) patients who experienced multidrug resistance
All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.
研究概览
详细说明
- It has been one of unsolved issues and unmet needs in CHB management to develop an optimal combination regimen to manage multidrug resistant HBV characterized by selection of variants with two or more classes A of signature genotypic resistant mutations1-3
- Currently adding on Adefovir(ADV) has been generally recommended in Lamivudine(LAM)- or Telbivudine(LdT)-resistant patients but little is known about the optimal management of CHB patients who developed multidrug resistance4
- Recent report has shown that the combination of LAM plus ADV did not suppress HBV DNA effectively in CHB patients with resistance mutations to both drugs. Only 12.2% of these pts achieved virologic response(VR; HBV DNA <60 IU/mL) at 12 months and multivariable analysis showed that LAM+ADV group and the presence of the rtA181V/T mutation were independently associated with a decreased rate of virologic response (HBV DNA <2,000 IU/ml) at 12 months4
- ETV has been demonstrated to be effective in patients with ADV resistance but not in patients with proven YMDD mutation. In contrast, TDF has been shown to be effective in patients with YMDD mutation but not necessarily in all patients with ADV resistance.1-3
- Thus theoretically, the combination of the most potent nucleoside analogue and nucleotide analogue with non-overlapping resistance profiles, such as ETV plus TDF, is expected to be a promising salvage treatment for multidrug resistant HBV but clinical evidence is limited
- Therefore, this study will explore that adequate management of multidrug resistant patients using ETV plus TDF combination may lead to faster and greater viral suppression and prevent further emergence of antiviral resistance
All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.
研究类型
介入性
注册 (预期的)
90
阶段
- 第四阶段
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
20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:
- ≥ 20 years of age
- History of HBsAg positive for more than 6 months
- Subject who has a history of genotypic resistance to NAs from two different classes A
- Detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks
- HBeAg-positive and -negative
- Compensated liver disease (Child-Pugh A)
- Signed written informed consent after being instructed about the objective and procedure of the clinical study
Exclusion Criteria:
- Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
- Co-infected with hepatitis C virus(HCV) or HIV
- Pregnant or lactating woman
- Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion
- History of liver transplantation or planned for liver transplantation
- Subject who was diagnosed malignant tumor and has been receiving chemotherapy
- Subject who has hepatocellular carcinoma(HCC) history or who shows potential HCC finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
- Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
- Patient who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)
- Subject who has a history of hypersensitivity to study drug or its ingredients
- Subject who is involved in other clinical trial within 60 days prior to study entry
- Subject who the investigator deems inappropriate to participate in this study
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 |
|---|---|
|
实验性的：Entecavir 1.0mg + Tenofovir 300mg
All subjects will orally take investigational drugs once daily for 48 weeks.
|
Entecavir 1.0mg + Tenofovir 300mg
其他名称：
|
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 |
|---|---|---|
|
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48
大体时间：at Week 48
|
To evaluate the proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time Polymerase chain reaction(PCR) at Week 48 after Entecavir plus Tenofovir combination therapy
|
at Week 48
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Virologic, serologic, biochemical efficacy and safety profile, as measured by the incidence of clinical adverse events and laboratory abnormalities including renal marker
大体时间：Week 4, 12, 24, 36, and 48
|
To evaluate virologic, serologic and biochemical response and safety of Entecavir plus Tenofovir combination therapy for 48 weeks
|
Week 4, 12, 24, 36, and 48
|
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。
调查人员
- 首席研究员：Sang Hoon Ahn, MD, PhD、Yonsei University
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
2012年8月1日
初级完成 (预期的)
2014年4月1日
研究完成 (预期的)
2014年4月1日
研究注册日期
首次提交
2012年5月7日
首先提交符合 QC 标准的
2012年5月8日
首次发布 (估计)
2012年5月9日
研究记录更新
最后更新发布 (估计)
2014年1月31日
上次提交的符合 QC 标准的更新
2014年1月30日
最后验证
2014年1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.
慢性乙型肝炎的临床试验
-
Lapo Alinari招聘中伴有 MYC、BCL2 和 BCL6 重排的复发性高级别 B 细胞淋巴瘤 | 具有 MYC、BCL2 和 BCL6 重排的难治性高级 B 细胞淋巴瘤 | 伴有 MYC 和 BCL2 或 BCL6 重排的复发性高级别 B 细胞淋巴瘤 | 具有 MYC 和 BCL2 或 BCL6 重排的难治性高级 B 细胞淋巴瘤 | 复发性弥漫性大 B 细胞淋巴瘤活化 B 细胞型 | 难治性弥漫性大 B 细胞淋巴瘤活化 B 细胞型 | 将惰性 B 细胞非霍奇金淋巴瘤转化为弥漫性大 B 细胞淋巴瘤 | 复发性弥漫性大 B 细胞淋巴瘤生发中心 B 细胞型 | 难治性弥漫性大 B 细胞淋巴瘤生发中心 B 细胞型美国
-
Northwestern UniversityNational Cancer Institute (NCI)主动，不招人弥漫性大 B 细胞淋巴瘤 | 弥漫性大 B 细胞淋巴瘤，未另行说明 | 高级 B 细胞淋巴瘤，未另行说明 | 富含 T 细胞/组织细胞的大 B 细胞淋巴瘤 | 具有 MYC 和 BCL2 和/或 BCL6 重排的高级别 B 细胞淋巴瘤 | 弥漫性大 B 细胞淋巴瘤活化 B 细胞型 | 弥漫性大 B 细胞淋巴瘤生发中心 B 细胞型美国
-
Ohio State University Comprehensive Cancer Center招聘中弥漫性大 B 细胞淋巴瘤 | 高级别 B 细胞淋巴瘤 | 弥漫性大 B 细胞淋巴瘤，未另行说明 | 弥漫性大 B 细胞淋巴瘤生发中心 B 细胞型美国
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Amgen主动，不招人复发性弥漫性大 B 细胞淋巴瘤 | 难治性弥漫性大 B 细胞淋巴瘤 | CD20阳性 | I 期弥漫性大 B 细胞淋巴瘤 | II 期弥漫性大 B 细胞淋巴瘤 | III 期弥漫性大 B 细胞淋巴瘤 | IV 期弥漫性大 B 细胞淋巴瘤美国
-
Curocell Inc.招聘中高级别 B 细胞淋巴瘤 | 弥漫性大 B 细胞淋巴瘤 (DLBCL) | 原发性纵隔大 B 细胞淋巴瘤 (PMBCL) | 转化的滤泡性淋巴瘤 (TFL) | 难治性大 B 细胞淋巴瘤 | 复发性大 B 细胞淋巴瘤大韩民国
-
National Cancer Institute (NCI)招聘中高级别 B 细胞淋巴瘤 | 弥漫性大 B 细胞淋巴瘤，未另行说明 | 将惰性 B 细胞非霍奇金淋巴瘤转化为弥漫性大 B 细胞淋巴瘤美国
-
Nathan DenlingerBristol-Myers Squibb招聘中B 细胞非霍奇金淋巴瘤复发 | 弥漫性大 B 细胞淋巴瘤复发 | 滤泡性淋巴瘤-复发性 | 高级别 B 细胞淋巴瘤-复发 | 原发性纵隔大 B 细胞淋巴瘤复发 | 惰性 B 细胞非霍奇金淋巴瘤转化为弥漫性大 B 细胞淋巴瘤复发 | 难治性 B 细胞非霍奇金淋巴瘤 | 难治性弥漫性大 B 细胞淋巴瘤 | 滤泡性淋巴瘤难治性 | 高级别 B 细胞淋巴瘤难治性 | 原发性纵隔大 B 细胞淋巴瘤难治性 | 将惰性 B 细胞非霍奇金淋巴瘤转化为难治性弥漫性大 B 细胞淋巴瘤美国
-
National Cancer Institute (NCI)主动，不招人
-
Northwestern UniversityNational Cancer Institute (NCI)招聘中复发性原发性纵隔（胸腺）大 B 细胞淋巴瘤 | 难治性原发性纵隔（胸腺）大 B 细胞淋巴瘤 | 伴有 MYC、BCL2 和 BCL6 重排的复发性高级别 B 细胞淋巴瘤 | 具有 MYC、BCL2 和 BCL6 重排的难治性高级 B 细胞淋巴瘤 | 复发性弥漫性大 B 细胞淋巴瘤，未另行说明 | 难治性弥漫性大 B 细胞淋巴瘤，未另行说明 | 复发性侵袭性 B 细胞非霍奇金淋巴瘤 | 难治性侵袭性 B 细胞非霍奇金淋巴瘤 | 复发性转化 B 细胞非霍奇金淋巴瘤 | 难治性转化 B 细胞非霍奇金淋巴瘤 | EBV 阳性弥漫性大 B 细胞淋巴瘤，未另行说明 | 高级 B 细胞淋巴瘤，未另行说明 | 与慢性炎症相关的弥漫性大 B 细胞淋巴瘤 | 伴 IRF4... 及其他条件美国
-
Patrick C. Johnson, MDAstraZeneca招聘中难治性 B 细胞非霍奇金淋巴瘤 | 弥漫性大 B 细胞淋巴瘤 (DLBCL) | 3b 级滤泡性淋巴瘤 | 难治性侵袭性 B 细胞淋巴瘤 | 侵袭性 B 细胞 NHL | 从头或转化的惰性 B 细胞淋巴瘤 | DLBCL，Nos 遗传亚型 | 富含 T 细胞/组织细胞的大 B 细胞淋巴瘤 | EBV 阳性 DLBCL，编号 | 原发性纵隔 [胸腺] 大 B 细胞淋巴瘤 (PMBCL) | 高级 B 细胞淋巴瘤，编号 | C-MYC/BCL6 双重打击高级别 B 细胞淋巴瘤 | C-MYC/BCL2 双重打击高级别 B 细胞淋巴瘤美国