Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
2012년 7월 19일 업데이트: 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.
연구 개요
연구 유형
중재적
등록 (실제)
1053
단계
- 2 단계
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
16년 이상 (어린이, 성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Entecavir, 1.0 mg, with or without lamivudine
|
Tablets, Oral, 1.0 mg, once daily
다른 이름들:
Oral, 100 mg, daily
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay
기간: 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
기간: Study entry to Week 192
|
Study entry to Week 192
|
|
|
Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay
기간: Baseline to Week 192
|
Observed values.
|
Baseline to Week 192
|
|
Overall Study: Mean HBV DNA Level by PCR Assay
기간: 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)
기간: Study entry to Week 216
|
Observed values.
|
Study entry to Week 216
|
|
Overall Study: Percentage of Participants With HBeAg Seroconversion
기간: 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
기간: Study entry to Week 216
|
Observed values.
|
Study entry to Week 216
|
|
Overall Study: Percentage of Participants Who Achieved ALT Normalization
기간: 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)
기간: 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)
기간: 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
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2001년 1월 1일
기본 완료 (실제)
2009년 12월 1일
연구 완료 (실제)
2011년 4월 1일
연구 등록 날짜
최초 제출
2011년 9월 16일
QC 기준을 충족하는 최초 제출
2011년 9월 21일
처음 게시됨 (추정)
2011년 9월 22일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2012년 8월 23일
QC 기준을 충족하는 마지막 업데이트 제출
2012년 7월 19일
마지막으로 확인됨
2012년 7월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- AI463-901
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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