Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
研究概览
详细说明
To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Ontario
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Toronto、Ontario、加拿大、M5T 2S8
- University of Toronto
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California
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Los Angeles、California、美国、90095
- University of California Los Angeles
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Los Angeles、California、美国、90048
- Cedars Sinai Medical Center
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San Francisco、California、美国、94143
- University of California San Francisco
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San Francisco、California、美国、94115
- California Pacific Medical Center
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Hawaii
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Honolulu、Hawaii、美国、96813
- Queen's Medical Center
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Maryland
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Bethesda、Maryland、美国、20892
- NIH Clinical Center
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Massachusetts
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Boston、Massachusetts、美国、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor、Michigan、美国、48109
- University of Michigan Health System
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Minnesota
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Minneapolis、Minnesota、美国、55446
- University of Minnesota
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Rochester、Minnesota、美国、55905
- Mayo Clinic
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Missouri
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Saint Louis、Missouri、美国、63110
- Washington University
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Saint Louis、Missouri、美国、63104
- Saint Louis University
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North Carolina
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Chapel Hill、North Carolina、美国、27599
- University of North Carolina
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Durham、North Carolina、美国、27710
- Duke University Medical Center
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Texas
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Dallas、Texas、美国、75390
- University of Texas Southwestern
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Dallas、Texas、美国、75246
- Baylor University Medical Center
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Virginia
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Richmond、Virginia、美国、23498
- Virginia Commonwealth University
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Washington
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Seattle、Washington、美国、98101
- Virginia Mason Medical Center
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Seattle、Washington、美国、98105
- University of Washington Medical Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
- >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
- Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
- Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
- Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
- ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, & the final value within 6 weeks prior to baseline visit.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging & shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria:
- History of hepatic decompensation
- Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin <3.5 g/dL.
- Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last screening visit.
- Previous treatment with medications that have established activity against HBV including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of prior HBV treatment & a wash-out period >24 weeks are not excluded.
- Known allergy or intolerance to study medications.
- Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
- Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.
- History of alcohol or drug abuse within 48 weeks of baseline visit.
- Previous liver or other organ transplantation (including engrafted bone marrow).
- Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
- Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
- Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
- History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
- Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
- Concomitant use of complementary or alternative medications purported to have antiviral activity.
- Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
学习计划
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:Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
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Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
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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每人每年严重不良事件 (SAE) 的发生率
大体时间:从第一次治疗到治疗结束(最长 48 周)和随访结束(最长 96 周)
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发生率的计算方法是 SAE 的数量除以观察的人年数,即所有参与者从治疗开始到治疗结束或随访结束之间的年数总和-向上,分别。
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从第一次治疗到治疗结束(最长 48 周)和随访结束(最长 96 周)
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Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL
大体时间:End of follow-up (up to 96 weeks)
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Lack of data was considered to be treatment failure.
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End of follow-up (up to 96 weeks)
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Incidence of Adverse Events (AEs) Per Person-Year of Observation
大体时间:From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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The number of AEs includes both AEs and Serious Adverse Events (SAEs).
The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
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From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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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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HBeAg 血清学转换的参与者比例
大体时间:治疗结束(最多 48 周)
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治疗结束(最多 48 周)
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HBeAg 血清学转换的参与者比例
大体时间:随访结束(最长 96 周)
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随访结束(最长 96 周)
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HBsAg 血清转化的参与者比例
大体时间:治疗结束(最多 48 周)
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治疗结束(最多 48 周)
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HBsAg 血清转化的参与者比例
大体时间:随访结束(最长 96 周)
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随访结束(最长 96 周)
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HBV DNA ≤1000 IU/mL 的参与者比例
大体时间:治疗结束(最多 48 周)
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治疗结束(最多 48 周)
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HBV DNA ≤1000 IU/mL 的参与者比例
大体时间:随访结束(最长 96 周)
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随访结束(最长 96 周)
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Proportion of Participants With HBeAg Loss
大体时间:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBeAg Loss
大体时间:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBsAg Loss
大体时间:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBsAg Loss
大体时间:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women
大体时间:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women
大体时间:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
大体时间:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
大体时间:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
大体时间:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
大体时间:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Absence of Detectable Antiviral Drug-resistance HBV Mutations
大体时间:End of treatment (up to 48 weeks)
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HBV drug resistance variant testing was performed at the CDC laboratory.
The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing.
Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.
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End of treatment (up to 48 weeks)
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合作者和调查者
调查人员
- 学习椅:Averell Sherker, MD、National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- 首席研究员:Anna Lok, MD、University of Michigan
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (美国 NIH 拨款/合同)
- UL1TR001111 (美国 NIH 拨款/合同)
- U01DK082916 (美国 NIH 拨款/合同)
- U01DK082864 (美国 NIH 拨款/合同)
- U01DK082874 (美国 NIH 拨款/合同)
- U01DK082944 (美国 NIH 拨款/合同)
- U01DK082843 (美国 NIH 拨款/合同)
- U01DK082871 (美国 NIH 拨款/合同)
- UL1TR000004 (美国 NIH 拨款/合同)
- A-DK-3002-001 (其他赠款/资助编号:Interagency agreement with NIDDK)
- U01DK082863 (美国 NIH 拨款/合同)
- U01DK082866 (美国 NIH 拨款/合同)
- U01DK082867 (美国 NIH 拨款/合同)
- U01DK082872 (美国 NIH 拨款/合同)
- U01DK082919 (美国 NIH 拨款/合同)
- U01DK082923 (美国 NIH 拨款/合同)
- U01DK082927 (美国 NIH 拨款/合同)
- U01DK082943 (美国 NIH 拨款/合同)
- UL1TR000058 (美国 NIH 拨款/合同)
- P30DK050306 (美国 NIH 拨款/合同)
- M01RR000040 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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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Entecavir and peginterferon的临床试验
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USDA Grand Forks Human Nutrition Research CenterCalifornia Polytechnic State University-San Luis Obispo完全的
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Dana-Farber Cancer Institute邀请报名