Phase 2
Completed N=1,051
Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
Hepatitis B Virus · HBV
Source: ClinicalTrials.gov NCT01438424 ↗
Enrolled (actual)
1,051
Serious AEs
16.1%
Results posted
Aug 2012
Primary outcomePrimary: 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 — 18; 9; 169; 14 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
18; 9; 169; 14; 900; 203 | — |
| PRIMARY Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240 |
49; 226; 109; 51; 226; 214 | — |
| PRIMARY 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 |
179; 126; 13; 38; 57; 61 | — |
| PRIMARY 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 |
44; 76; 285; 148; 68; 106 | — |
| PRIMARY 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 |
13; 17; 107; 13; 842; 156 | — |
| PRIMARY 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 |
18; 27; 135; 11; 862; 174 | — |
| PRIMARY 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) |
100; 21 | — |
| SECONDARY Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay |
17; 63; 67; 73; 78 | — |
| SECONDARY Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay |
28; 76; 77; 81; 85 | — |
| SECONDARY Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay |
17; 4; 8; 8; 12; 13 | — |
| SECONDARY Overall Study: Mean HBV DNA Level by PCR Assay |
6.14; 3.87; 3.62; 3.37; 3.31; 3.34 | — |
| SECONDARY Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg) |
34; 40; 42; 46; 45; 50 | — |
| SECONDARY Overall Study: Percentage of Participants With HBeAg Seroconversion |
30; 33; 34; 36; 32; 34 | — |
| SECONDARY Overall Study: Mean Alanine Transaminase (ALT) Levels |
109.4; 48.77; 42.10; 37.06; 38.10; 39.30 | — |
| SECONDARY Overall Study: Percentage of Participants Who Achieved ALT Normalization |
40; 75; 74; 78 | — |
| SECONDARY Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort) |
73; 96 | — |
| SECONDARY Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort) |
32; 88 | — |
| SECONDARY Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay |
18 | — |
| SECONDARY 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) |
55; 83; 89; 91; 94; 1 | — |
| SECONDARY 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) |
88; 87; 83; 91; 79; 95 | — |
| SECONDARY 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) |
58; 25; 8; 76 | — |
| SECONDARY Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort) |
65; 68 | — |
| SECONDARY Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort) |
97; 81 | — |
| SECONDARY Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort) |
99; 85 | — |
| SECONDARY 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) |
10; 10; 7; 3; 14; 31 | — |
| SECONDARY Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort) |
1.54; 1.18 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT01438424). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.