Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
2012年7月19日 更新者：Bristol-Myers Squibb
A Preliminary Assessment of Safety and Antiviral Activity of Open-label Entecavir in Subjects With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
The purpose of this study is to provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up.
研究概览
研究类型
介入性
注册 (实际的)
1053
阶段
- 阶段2
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
16年 及以上 (孩子、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
Key inclusion criteria:
- Age of 16 years and older
- Receipt of entecavir or lamivudine in a previous entecavir study.
Participants who were, based on their response to entecavir:
- Virologic nonresponders at Week 48
- Partial virologic responders who became nonresponders during the second year of treatment
- Partial virologic responders at Week 96
Complete responders who relapsed during postdosing follow-up
- Decompensated liver disease in AI463-048 that met 1 or more of the following criteria:
- Nonresponse to adefovir after at least 24 weeks of treatment
- Partial response to adefovir after 96 weeks of treatment
- Complete response to adefovir after relapsing during postdosing follow-up
Demonstrated intolerance to adefovir
- Except for those participants enrolled from AI463-048, compensated liver disease.
Key exclusion criteria:
- HIV coinfection
- Receiving nephrotoxic or hepatotoxic agents
- Ongoing opportunistic infections
- Hemoglobin level <11.0 g/dL except for those enrolled from AI463-048
- Platelet count <70,000 mm^3 except for those enrolled from AI463-048
- Absolute granulocyte count <1,500 cells/mm^3
- Recent history of pancreatitis (within 24 weeks prior to first dose of therapy)
- Current evidence of ascites requiring paracentesis, hepatic encephalopathy, or variceal bleeding, except for those enrolled from AI463-048
- Known history of allergy to nucleoside analogues.
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, 1.0 mg, with or without lamivudine
|
Tablets, Oral, 1.0 mg, once daily
其他名称：
Oral, 100 mg, daily
|
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 |
|---|---|---|
|
Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs
大体时间：Continuously from Day 1 through Week 240
|
An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment.
An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling.
ALT=alanine transaminase; ULN=upper limit of normal.
|
Continuously from Day 1 through Week 240
|
|
Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240
大体时间：Day 1 of treatment through Week 240
|
Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0;
Gr 2=8.0-<9.5;
Gr 3=6.5-<8.0;
Gr 4=<6.5 White blood cells (cells/mm^3): Gr 1=2,500-<4,000; Gr 2=1,000-<2,500; Gr 3=800-<1,000; Gr 4=<800.
Neutrophils (cells/mm^3): Gr 1=1000-<1500; Gr 2=750-<1000; Gr 3=500-<750; Gr 4=<500.
Platelets (cells/mm^3): Gr 1=75,000-99,000; Gr 2=50,000-<75,000; Gr 3=20,000-<50,000; Gr 4=<20,000.
Prothrombin time (seconds): Gr 1=1.01-<1.26*ULN;
Gr 2=1.26-<1.51
*ULN; Gr 3=1.51-3*ULN;
Gr 4=>3*ULN.
INR: Gr 1=1.24-1.5;
Gr 2=1.5-2;
Gr 3=2-3; Gr 4=>3.
INR=international normalized ratio; ULN=upper limit of normal. .
|
Day 1 of treatment through Week 240
|
|
Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing
大体时间：Day 1 of treatment through Week 240
|
Amylase: Grade 1=1.10-<1.40*ULN;
Grade 2=1.40-< 2.10*ULN; Grade 3=2.10-5.00*ULN;
Grade 4=>5.00*ULN.
Lipase: Grade 1.1-<1.4*ULN;
Grade 2=1.4-<2.1*ULN;
Grade 3=2.1-5.0*ULN;
Grade 4=>5.0*ULN.
Creatinine: Grade 1=1.10-< 1.60*ULN; Grade 2=1.60-<3.10*ULN;
Grade 3=3.10-6.00*ULN;
Grade 4=>6.00*ULN.
Blood urea nitrogen (BUN): Grade 1=1.25-<2.60*ULN;
Grade 2=2.60-<5.10*ULN;
Grade 3=5.10-10*ULN;
Grade 4=>10*ULN.
ULN=upper limit of normal.
|
Day 1 of treatment through Week 240
|
|
Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing
大体时间：Day 1 of treatment through Week 240
|
Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-<90; Gr 3=80-<85; Gr 4=40-<80.
Hyperchloremia: Gr 1=113-<117; Gr 2=117-<121; Gr 3=121-125; Gr 4>125.
Hypocarbia: Gr 1=19-21; Gr 2=15-<19; Gr 3=41-45; Gr 4=>45.
Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=>45.
Hyponatremia: Gr 1=130-132; Gr 2=123-<130; Gr 3=116-<123; Gr 4<116.
Hypernatremia: Gr 1=148-<151; Gr 2=151-<158; Gr 3=158-165; Gr 4=>165.
Hypokalemia: Gr 1=3-3.4;
Gr 2=2.5-<3;
Gr 3=2-<2.5;
Gr 4=<2.
Hyperkalemia: Gr 1=5.6-<6.1;
G2=6.1-<6.6;
Gr 3=6.6-7;
Gr 4=>7.
Hypoglycemia: Gr 1=55-64; Gr 2=40-<55; Gr 3=30-< 40; G4=-<30.
Hyperglycemia: Gr 1=116-<161; Gr 2=161-<251; Gr 3=251-500; Gr 4>500.
|
Day 1 of treatment through Week 240
|
|
Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
大体时间：Continuously from Day 1 through Week 144
|
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment.
An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling.
AST=aspartate aminotransferase; ULN=upper limit of normal.
|
Continuously from Day 1 through Week 144
|
|
Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
大体时间：Continuously from Day 1 through Week 192
|
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment.
An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling.
ALT=alanine aminotransferase; ULN=upper limit of normal.
|
Continuously from Day 1 through Week 192
|
|
Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)
大体时间：End of dosing to Week 48 off-treatment follow-up
|
The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.
|
End of dosing to Week 48 off-treatment follow-up
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay
大体时间：Study entry to Week 192
|
Study entry to Week 192
|
|
|
Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay
大体时间：Study entry to Week 192
|
Study entry to Week 192
|
|
|
Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay
大体时间：Baseline to Week 192
|
Observed values.
|
Baseline to Week 192
|
|
Overall Study: Mean HBV DNA Level by PCR Assay
大体时间：Study entry to Week 216
|
Study entry to Week 216
|
|
|
Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)
大体时间：Study entry to Week 216
|
Observed values.
|
Study entry to Week 216
|
|
Overall Study: Percentage of Participants With HBeAg Seroconversion
大体时间：Study entry to Week 216
|
Observed values.
Seroconversion=negative HBeAg with detectable anti-HBe antibody.
|
Study entry to Week 216
|
|
Overall Study: Mean Alanine Transaminase (ALT) Levels
大体时间：Study entry to Week 216
|
Observed values.
|
Study entry to Week 216
|
|
Overall Study: Percentage of Participants Who Achieved ALT Normalization
大体时间：Study entry to Week 216
|
ULN=upper limit of normal.
ALT normalization=ALT levels ≤1.0*ULN.
|
Study entry to Week 216
|
|
Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)
大体时间：Baseline to Week 192
|
The Knodell Histologic Activity Index scores stage of necrosis and grade of inflammation in liver biopsies.
Components are necrosis near the portal vein, intralobular degeneration and focal necrosis, portal inflammation, and fibrosis.
The 4 components are scored from 1 to 4 and 1 to 10 (necrosis near the portal vein) and combined for a total score, with 22 being the highest possible score.
Higher the score for each component=greater liver damage.
Histologic improvement=a ≥2-point reduction in total Knodell score and no worsening in fibrosis.
Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell necroinflammatory scores ≥2.
|
Baseline to Week 192
|
|
Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)
大体时间：Baseline to Week 192
|
The Ishak Modification for Hepatic Activity Index (HAI) scores necroinflammatory activity in chronic hepatitis.
0=no fibrosis, 1=fibrosis expansion of some portal areas, 2=fibrosis expansion of most portal areas, 3=fibrosis expansion of most portal areas with occasional bridging, 4=fibrosis expansion of portal areas with marked bridging, 5=incomplete cirrhosis, 6=probable or definite cirrhosis.
Higher score=more severe necrosis.
Improvement in fibrosis=≥1-point reduction in HAI score.
Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell scores ≥2.
|
Baseline to Week 192
|
|
Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay
大体时间：Baseline to Week 144
|
Baseline to Week 144
|
|
|
Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)
大体时间：Baseline to Weeks 48, 96, 144, 192, and 240
|
The Entecavir Continuous Treatment Cohort consisted of participants from study AI463-022 (NCT00035633) who were nucleoside-naive HBeAg-positive and enrolled in the current study with ≤35 days off treatment between the last dose in AI463-022 and the first dose in the current.
This cohort is considered to be on continuous entecavir treatment and permitted assessment of continuous administration of entecavir in AI463-022 and the current study.
|
Baseline to Weeks 48, 96, 144, 192, and 240
|
|
Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)
大体时间：Baseline to Weeks 48, 96, and 144
|
The Entecavir Retreatment Cohort consisted of participants who were nucleoside-naive, HBeAg-negative and enrolled from BMS study AI463-027 with >60 days off treatment between the last dose in AI463-027 and the first dose in the current study.
This cohort permitted assessment of entecavir, 1.0 mg, provided as retreatment in the current study.
|
Baseline to Weeks 48, 96, and 144
|
|
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
大体时间：Baseline to Week 96
|
The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study.
This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
|
Baseline to Week 96
|
|
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
大体时间：Baseline to Week 144
|
The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study.
This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
|
Baseline to Week 144
|
|
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
大体时间：Baseline to Week 96
|
The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with >60 days between end of dosing in AI463-027 and the switch to entecavir in the current study.
This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
|
Baseline to Week 96
|
|
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
大体时间：Baseline to Week 144
|
The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with >60 days between end of dosing in AI463-027 and the switch to entecavir in the current study.
This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
|
Baseline to Week 144
|
|
Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)
大体时间：End of dosing to Weeks 48 and 96 off-treatment follow-up
|
The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR Assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.
ULN=upper limit of normal.
|
End of dosing to Weeks 48 and 96 off-treatment follow-up
|
|
Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)
大体时间：End of dosing to Weeks 48 and 96 off-treatment follow-up
|
The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.
|
End of dosing to Weeks 48 and 96 off-treatment follow-up
|
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
2001年1月1日
初级完成 (实际的)
2009年12月1日
研究完成 (实际的)
2011年4月1日
研究注册日期
首次提交
2011年9月16日
首先提交符合 QC 标准的
2011年9月21日
首次发布 (估计)
2011年9月22日
研究记录更新
最后更新发布 (估计)
2012年8月23日
上次提交的符合 QC 标准的更新
2012年7月19日
最后验证
2012年7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.